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Our goal... “Eradicating anemia for safer motherhood & healthier generations” Bangalore Society of Obstetrics & Gynaecology www.bsog.in 1

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Page 1: Anemia Monograph

Our goal...

“Eradicating anemia for safer motherhood & healthier generations”

Bangalore Society of Obstetrics & Gynaecologywww.bsog.in

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Page 2: Anemia Monograph

BANGALORE SOCIETY OF OBSTETRICS AND GYNAECOLOGY

TEAM BSOG 2007- 2008

Office bearers:

President: Dr. Arulmozhi Ramarajan Hon. Secretary: Dr. Harsha N Biliangady Hon. Treasurer: Dr. Parvati Javali Vice President: Dr. Reeta H Biliangady President Elect: Dr. Susheela Rani B S Hon. Joint Secretary: Dr. Jyothika A Desai

Executive Committee:

Dr. Chandrika M Dr. Devika Gunasheela Dr. Jayanthi T Dr. Lata Venkataram Dr. Malini K V Dr. Nagarathnamma Dr. Parimala Devi Dr. Swetha Arasu Dr. Venkatesh N Dr. Vidya Bhat

Invited members:

Dr. Kamini A RaoDr. Hema Divakar

Co-opted members:

Dr. Prakash K MehtaDr. Sheela V ManeDr. Sita BhatejaDr. Sunanda KulkarniDr. Vaijayanthi N V

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We can make a difference…

In our population, anemia appears to be the rule rather than the exception. No age seems to be

exempt. It cuts lives short. It runs as an undercurrent in many premature deaths. It brings down

an individual's productivity and thereby affects the nation's economy. Most importantly, it is

largely preventable & easily treatable. This is where we can make a difference. By preventing,

treating anemia in one woman, we will be giving that family a healthy mother who will be pivotal

in raising a healthy and happy family.

This monograph on anemia is to help understand the ailment better, to help eradicate it from our

society. It is a small effort to put together important aspects of the disease, its causes, presentation,

diagnosis and management, in a simple fashion to make it a ready reference for the practicing

Obstetricians, Gynecologists and family physicians.

Eminent practitioners and senior teachers have contributed chapters in this monograph. The

pages take us through an overview of the problem, a historical note, its presentation through the

different stages in life, the types of anemia, investigations and management. A write up on the

judicious use of blood and blood products adds color to the book. The case reports from our own

members give a personal and clinical touch to the issue.

I express my deep sense of gratitude to all the authors, who have taken precious time off to add

value to the book. My special thanks are due to Dr. Pankaj Desai and Dr. Kamini A Rao for their

forewords and words of encouragement. I am grateful to my friends Dr. Prakash K Mehta and

Dr. Susheela Rani B S for their help in structuring and editing. I express my sincere thanks to

Dr. Reddy's Labs for bringing out this book.

Dr. Arulmozhi RamarajanPresident, BSOG 2007-08

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FOREWORD

Anemia seems to haunt Indians since mythological days. Pandu the patriarch of the Pandavas

was believed to be suffering from this condition. Traditionally we have been defining anemia as

hemoglobin less than 10 gms%. However, time may have come to review this definition as we

Indians seem to be comfortable at a shade lower of hemoglobin levels. This is not to dilute the

efforts of anemia eradication but putting a poser to research scientists on this matter. Do we

Indian have a tendency to have lower hemoglobin? Well as of now it is anybody's guess. Obstetrics they say is a "bloody" business. Having to face hemorrhage when the mother is already

anemic is like pushing her over the brink from the edge. The traditional definition of hemorrhage

pegging the amount of blood loss at > 500 ml too goes for a toss when you see it in the light of an

anemic mother. Therefore Indian obstetricians wisely define hemorrhage clinically rather than

waiting for the blood loss to go upto 500 ml. In anemic subjects this could be lethal. Understandably, nutritional causes remain in focus in most discussions on anemia. However in

India there are vast belts where non-nutritional anemia too has a firm grip in form of sickle cell

anemia or Thalassemia. Interestingly the distribution of Thalassemia throughout the world

explains mysteries of movements of land masses. The way Thalassemia occurrence is distributed,

it shows that Australia and its nearby areas including Fiji, Papua New Guinea and New Zealand

where all one land mass with Asia. Seismologicaly now thought to be the most stable part of the

earth Australia, was separated from Asia ironically through an earthquake carrying along the

genes of Thalassemia. Thus anemia is not only of interest to doctors but also to geologists!

What was a very popular route of iron administration: I.V. Total dose Iron administration has

thankfully lost its popularity of the 80s. It was very hazardous and life endangering which

looking at the risk-benefit ratio was untenable. It is also interesting to know that any oral iron

preparation if does not produce some amount of gastric side effects, is ineffective. Thus when a

pharmaceutical company tries to sell you an iron preparation with no gastric side-effects, rest

assured it is also ineffective!

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FOGSI philosophy for 2007 is FOGSI Cares 2007. In this FOGSI also cares for anemic adolescents.

So as to catch them young: we at FOGSI are focusing on identification of anemic young girls so

that by the time they approach motherhood they are no more anemic. In this it will be pertinent to

state that one more point where anemic motherhood can be averted is by treating anemia in

women who come for infertility treatment. This is a point where before treating her infertility we

can make her non-anemic so that when she is safe on this count from dangers in child bearing. I commend Bangalore O & G society for taking up this theme in a big way.

Dr. Pankaj DesaiPresidentFederation of Obstetric & Gynecological societies of India

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FOREWORD

Anaemia is a major public health hazard in India affecting all segments of the population in

general and children, women and pregnant women in particular. It is the single most important

cause of maternal morbidity and mortality contributing directly to 20% of maternal deaths and

indirectly to a further 20%. What is doubly distressing is that the most common cause of anaemia

in India is nutritional anaemia. Nutritional deprivation compounded by chronic blood loss due

to hookworm and malarial infestations as well as poor bio availability further enhances the

incidence and severity of anaemia.

In an era of hope kindled by awesome scientific advances, we in India are still battling with the

paradox of high maternal morbidity and mortality - much of it due to anaemia. Reducing the

burden of anaemia is essential to achieve the WHO's Millennium Development Goals relating to

maternal and childhood mortality. According to WHO, the strategy for control of anaemia

includes detection and appropriate management; prophylaxis against parasitic diseases and

supplementation with iron and folic acid; and improved obstetric care and management of

women with severe anaemia. Successful delivery of these cost effective interventions requires

the integrated efforts of several health programs particularly those targeted at pregnant women

and young children and the strengthening of health systems, increased community awareness

and financial investment on the part of the government.

Creating awareness about anaemia should be a major 'thrust issue' for each and every member of

the medical fraternity and this book aims to do just that. This Monograph covers each and every

aspect of the detection, management and prophylaxis of the various types of anaemia. The book

has been written in a lucid language with extensive diagrams, photographs and flow charts to

give clarity to the subject. I must congratulate Dr. Arulmozhi Ramarajan on this superlative

effort which I am sure will soon be an essential not only for physicians but also for medical

students, obstetricians, nurses as well as the paramedical fraternity.

Dr. Kamini A. Rao FOGSI Representative to FIGODirector, Bangalore Assisted Conception Centre

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"It is from numberless diverse acts of courage and

belief that human history is shaped. Each time a man

stands up for an ideal, or acts to improve the lot of

others, or strikes out against injustice, he sends forth a

tiny ripple of hope, and crossing each other from a

million different centers of energy and daring those

ripples build a current which can sweep down the

mightiest walls of oppression and injustice."

- Robert F. Kennedy -

“Eradicationg Anemia: Reaching the Unreached”

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SCIENTIFIC SECTION

CONTENTS

1. Anemia: Issues & Interventions Dr. Arulmozhi Ramarajan

2. Anemia through the ages Dr. Malathi Rao 3. Fetal anemias Dr. Ramamurthy B S 4. Childhood anemia Dr. Christi D Savio

5. Anemia in adolescence Dr. Sheela V Mane

6. Bolt from the blue: Anemia of acute blood loss Dr. Prakash K Mehta 7. Off color @ forty plus Dr. Devika Gunasheela 8. Hereditary anemias Dr. Hema Divakar

9. Acquired hemolytic anemias Dr. Biliangady Harsha N 10. Thalassemia in pregnancy Dr. Narayanan 11. Uncommon causes of anemia Dr. Latha Venkataram

12. Investigations: What, when & why? Dr. Jayanthy T

13. IDA in pregnancy Dr. Jyothika A Desai

14. Eating right – right from now! Dr. Sita Bhateja

15. Mirror, mirror on the wall…. Dr. Susheela Rani B S

16. Refractory anemia in pregnancy Dr. Biliangady Reeta H

17. Hemotherapy in ObG: When, why & how? Dr. Shivaram

18. Anemia in pregnancy - a teaching hospital experience Dr. Malini K V

19. Blood banks in Bangalore Dr. Swetha Arasu & Dr. Teena Thomas

20. Case reports

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ANEMIA: ISSUES & INTERVENTIONS

Dr. Arulmozhi Ramarajan, MBBS, MD, DGO, PGDMLE

Consultant and Head of ObGynChurch of South India Hospital, Bangalore

INTRODUCTION:

Anemia is one of the world's most widespread health problems. It affects more than 2 billion

people worldwide, women and children being more affected. The word “anemia” in Greek

means "without blood." It is the generic name given to a group of disorders characterized by a

quantitative or qualitative deficiency of the circulating erythrocytes. In India, about 52% of the

women of reproductive age & 74% of children are anemic.

In a 2002 report, WHO lists iron deficiency, a major cause of anemia, as one of the top 10 risk

factors in developing countries, for “lost years of healthy life”. Conservative estimates suggest

anemia is the direct cause of 3 to 7 percent of maternal deaths worldwide. Other estimates

suggest it is the direct or indirect cause of 20 to 40 percent of maternal deaths. Reducing the

number of women dying in childbirth by 3/4ths by 2015 is one of the key goals of the Millennium

Declaration of the World Health Organization. This goal was agreed upon by world leaders from

189 countries at the UN Millennium Summit in September 2000. If we should bring down our

maternal mortality and morbidity, we need to tackle anemia on a war footing.

Non Industrialized Countries

Anemia Prevalence (WHO)

Age group Industrialized Countries

20.1% 39.0%Children 0 - 4 years

Children 5 - 14 years

Pregnant women

Women 15 - 59 years

Men 15 - 59 years

Elderly > 60 years

05.9% 48.1%

22.7% 52.0%

10.3% 42.3%

04.3% 30.0%

12.0% 45.2%

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ISSUES:

Anemia has serious negative consequences including increased mortality in women and children,

decreased capacity to learn, and reduced productivity in all individuals. Its devastating effects on

health, physical and mental productivity affect the quality of life and translate into significant

economic losses.

Women are vulnerable to malnutrition and anemia throughout their life cycle for both biological

and social reasons. Anemia begets anemia.

At birth, the hemoglobin level and iron stores depend upon the nutrient inputs from the mother.

A normal weight, full term infant that is born to a healthy mother and gets exclusively breastfed

manages enough iron from its own stores and from breast milk. The stored iron is exhausted in

about six months. Additional iron is then required because the iron content of unfortified

conventional complementary foods is insufficient to meet the high iron requirements of growing

6 to 24 months old infants and children. Infants and children who do not obtain adequate iron will

suffer cognitive impairment that will affect their ability to learn and to perform income earning

tasks later in life. The sad part is that subsequent supplementation of iron cannot correct the

cognitive impairment. Many of the girls who survive under such nutritional stress are stunted,

with little chance of recovery. Anemic children are apathetic and anorexic, do not have energy to

play, and have trouble learning. In societies with gender discrimination, girls face greater degrees

of deprivation in food, education and opportunities to bring out their best.

Adolescence is a period of rapid growth, and the requirements for iron are high. Adolescents are

particularly vulnerable to anemia caused by multiple nutritional deficiencies and helminth

infections. This increased requirement of iron continues throughout the reproductive years

because of menstrual blood loss, the iron demands of the developing fetus, and blood loss during

delivery. Teenage pregnancy is like adding fuel to fire. Anemia in the growing years makes these

Causes of Maternal Death and contribution of 3

Iron Deficiency Anemia (IDA)

Adapted from Khan et al, Lancet April 1 2006

Hemorrhage31%

HypertensiveDisorder 10%Unsafe Abortion

5%

Sepsis 11%

ObstructedLabor 7%

Indirect Causes

14%

HIV 3%

Other DirectCauses 5%

Unclassified6%

Anemia8% Deaths

Associatedwith IDA

22%

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children more susceptible to infections including tuberculosis, malaria and HIV.

Through the reproductive years, women in developing countries are pregnant, lactating or

pregnant and lactating. If they do have a break, it is highly likely that they have abnormal blood

loss during menses. Anemia is the rule rather than exception. Physical work capacity and fitness

are reduced in anemic women because iron is needed by the blood to carry oxygen to the brain

and muscles and by the muscles for normal functioning. Anemic women are more likely to

deliver low birth weight infants. They transfer less iron to their fetuses. And these infants are at

increased risk of becoming iron-depleted in early infancy. Anemic women are more susceptible

to puerperal sepsis.

Women with severe anemia are particularly at risk and have a 3.5 times greater chance of dying

from obstetric complications than women who do not have anemia. Anemia related fatigue also

makes the effort of labor more difficult, thus prolonging labor. Severe anemia can lead to heart

failure at the time of labor and delivery. Although it is currently accepted that only severe anemia

causes maternal mortality, it has been estimated that moderate anemia increases a woman's

chance of dying 1.35 times, making it a risk for maternal mortality. Many more women have mild

to moderate anemia than severe anemia. This emphasizes the importance of preventing and

treating all forms of anemia, as the number of deaths associated with mild to moderate anemia is

potentially greater than the number associated with severe anemia.

Various factors including lack of knowledge and awareness, cultural taboos, incorrect food

practices, infections and infestations, lack of access to services and poverty have contributed to

the continued prevalence of this much treatable disease. Anemia is frequently multifactorial.

While iron deficiency is the most common cause of anemia worldwide, genetic traits, such as

thalassemia and hemoglobinopathy (eg, sickle cell disease, glucose-6-phosphate dehydrogenase

deficiency, hemoglobin E disorder) should also be considered in people of Southeast Asian,

African, and Mediterranean descent. In cases of anemia unresponsive to treatment with iron

supplementation, hemoglobin electrophoresis should be performed once iron stores have been

replenished. Recognition, correct classification (diagnosis) and treatment are of the utmost

importance in the management of anemia.

INTERVENTIONS:

History has it that the Greek physicians equated iron with strength and treated weakness in

patients with water in which old swords had been left to rust. In the 17th century, Thomas

Sydenham used iron and steel filings steeped in Rhenish wine for the treatment of chlorosis, an

old name for iron deficiency anemia.

We are certainly better placed today, when it comes to interventions to eradicate anemia. The

methods are inexpensive and effective. As primary care physicians for women, Obstetricians

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have the means, the potential and a duty to achieve this goal of eradicating anemia. We can make

our women and children stronger and healthier, and this in turn will reflect in the overall growth

and development of the country.

Here's how we can contribute:

General measures:

v Health education to create and enhance anemia-awareness amongst our women, children

and health workers.

v Malaria and hookworm prevention and treatment particularly in endemic areas.

v Periodic iron and folic acid supplementation (60mg of iron and 400µg folic acid for 3 months)

for prepubertal and adolescent girls and for all women of childbearing age, in areas of high

prevalence of anemia.

v Certain drugs can cause megaloblastic anemia. Diphenyl hydantoin, barbiturates and oral

contraceptive agents interfere with folate absorption, and metformin that is widely used in

treating DM and PCOS interferes with B12 absorption. Those on long term therapy with these

drugs must be closely monitored.

In infancy & childhood:

v Delayed cord clamping in newborns has shown to increase their iron stores. However, caution

should be exercised in Rh Negative pregnancies, for fear of Rh isoimmunization and risk of

hemolysis in the neonate.

v Exclusive breastfeeding from within one hour of birth to at least six months of age. Avoidance

of prelacteal feeds is equally important.

v Inculcating good eating habits from a tender age is important.

v Introducing fortified foods is an effective way of preventing and treating deficiency disorders.

v Iron Folic Acid supplements & deworming for school children.

v Ensuring basic education to the girl child and empowering her for the life ahead.

In pregnancy:

v Providing at least 100mgs of iron for 100 days during pregnancy and continuing the same for

at least three months after delivery.

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v Routinely deworming pregnant women in the second or third trimester, or in the post partum

period. This should become as routine as giving tetanus toxoid, and is sure to reap bigger

benefits.

v Making deliveries safer, by reducing blood loss during delivery. Active management of the

third stage, use of prophylactic ergometrine / oxytocin / carboprost and taking care to avoid

traumatic deliveries are direct ways in which we can contribute to improved outcomes.

v Providing safe blood transfusions for women with severe anemia is extremely important and

life saving. In situations where a requirement for transfusion is anticipated, for example in

placenta previa / previous cesarean section / severe anemia / HELLP syndrome, one needs to

be adequately prepared.

In the post partum period:

v Encouraging exclusive breast feeding. This minimizes postpartum bleeding when initiated

within an hour of delivery. Additional benefits include lactational amenorrhoea which is a

saving on menstrual loss. It also contributes to a delay in the return of fertility. Thus even if the

woman has not accepted any specific contraceptive method, she is less likely to become

pregnant during lactation, and less likely to come asking for a termination of pregnancy.

v For those who accept oral contraceptive pills, taking IFA tablets during the “blank” weeks

should be emphasized.

v Injectable progesterone contraception should be promoted, for the added benefit of

amenorrhoea during its period of use.

v Monitoring blood loss in IUCD users is important. It is imperative to advise use of

antifibrinolytic / other styptic medication to reduce blood loss in the initial menstrual cycles.

Little drops of water make a mighty ocean, goes the saying. Let every mother and child count.

Let's do our bit to paint our nation pink.

References:

WHO Fact Sheet No. 276 / Feb 2004.

Khan et al. Lancet April 2006.

WHO The World Health Report: Reducing risks, promoting healthy life. Geneva, 2002.

Khanal P, Walgate R. Nepal deworming program ready to go worldwide. WHO Bulletin, 2002,

80: 423-424.

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National family Health Survey-India (NFHS-II) 1998-99, International Institute of Population

Sciences. Demographic Health Survey, 2000.

Survival for Women and Children (SWACH) Foundation. 1997. Anemia in Pregnant Women and

Adolescent Girls in Rural Areas of Haryana, India. Quarterly Progress Report: April to June 1997.

Awasthi S et al. Effectiveness and cost effectiveness of albendazole in improving nutritional

status of preschool children in urban slums – Indian Pediatrics 2000, 37, 19-29.

Concise hematology by H J Woodliff.

Allen LH (2000) Anemia & Iron Deficiency: Effects on pregnancy outcome. Am. J of clinical

nutrition 71: 1280S – 1284S.

Barbin B J, M Hakimi, D Pelletier (2001) An analysis of anemia & pregnancy – related maternal

mortality. J of nutrition 131: 604S – 615S.

Mahomed K (2000) Iron supplementation in pregnancy (Cochrane Review) in The Cochrane

Library, Issue 3, Oxford Update Software.

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“Anemia through the ages”

Dr. Malathi RaoMBBS. FRCS. FACOG

Manipal North side Hospital Bangalore

What is Anemia?

Anemia is a blood disorder characterized by abnormally low level of RBC in the body. It is

usually a sign of underlying disease.

Historical perspective:

Ancients recognized blood as life giving substance. Hebrews in patriarchal age maintained that

blood was the seat of the soul. In Mosaic Law blood is drained before an animal was prepared as

food (practice still followed by Jews).

Circulation of blood was stated by William Harvey in seventeeth century.

1637 – 80 Jan Swammerdam discovered what he called as “Ruddy globules” by looking at blood

through microscope (obviously RBC).

1739 – 74 – William Hewson who published his opinion posthumously that red cells were

present in such numbers, they have to be important. This earned him the title of “Father of

Hematology”.

In 19th century “Anemia” the word was used clinically to refer to pallor of skin, mucous

membrane etc.

1891 – Ehrlich developed triacd stain which allowed him to classify WBC into a scheme similar to

the one we use today.

1905 Gritav Giemsa found the giemsa stain and in 1906 J.H. Wright found wright stain, both of

which are in use routinely in clinical laboratories.

Era of modern Hematology is considered to have begun at Harvard Medical School with the

work of George Richards Minot and his assistant William Parry Murphy.

In 20th century Hematologists are able to diagnose, classify anemia easier, faster, and cheaper

and techniques are developed for treating them from simple nutritional and drug therapy to

advanced modalities like blood transfusion, bone marrow transplants and recently with stem

cell therapy. From this point the investigation of Anemia revolved around the molecular level.

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Iron deficiency Anemia (IDA)

History: A disease believed to be IDA is described in about 1500 BC in the Egyptian Eber’s

Papyrus. It was termed Chlorosis or green sickness in Medieval Europe and iron salts were used

for treatment in France by mid 17th century. Thomas Sydenham recommended iron salts as

treatment for chlorosis but treatment with iron was controversial until 20th century, when its

mechanism of action was more fully elucidated.

Current concepts: IDA is the most common form of malnutrition in the world and is the eight

leading cause of disease in girls and women in developing world. IDA is highly prevalent among

women of reproductive age in south East Asia – 50-70%, but the prevalence in pregnant women

remains at 63.5%.

Impact on pregnancy: Problem of under nutrition in India generally starts much earlier in life

with gender discrimination, menstrual loss, and socio economic status, multiparity, and late or no

ANC.Even interventions like reducing fertility and iron supplementation during pregnancy will

have beneficial effect but still leave most women iron deficient. Effects on pregnancy – Increased

preterm labor, a 2.6 fold increase in PPH and a 3.1 fold increase in low birth weight babies. All

pregnant women should receive prenatal care along with adequate iron supplementations to

decrease the poor outcome in pregnancy.

Anemia Causes And Types

Sickle cell A

Common Causes

A of acute blood loss

Hemolytic A

Inherited - Hereditary Sphrocytosis

Enzymatic pyruvate kinase

G6PD deficiencyAcquired - Drugs, Auto immune, physical

Agents, Micro angiopathic HA,

Paroxysmal nocturnal hemoglobin urea

Fanconi' A

Thalassemia

Sideroblastic A Iron deficiency A

Aplastic A. Megaloblastic A. Vit B 12 , Folic acid

Pernicious A. 80%, Post surgery,

Non megaloblastic macrocytosis

Anemia of chronic diseases

CancerChronic

InflammationAIDS Liver Disease Kidney Failure

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Megaloblastic Anemia

History:

1880 -Ehrlich distinguished between cells he termed megaloblasts in the blood in Pernicious

anemia from normoblasts.

1887 –Quinckle reported large and irregular red cells.

1921 – Zadek noted megaloblasts in the marrow in real life.

1923 – Naegeti described hyper-segmented netrophils in peripheral blood in PA.

1932 – Tempka and Braun described metamyelocytes in the marrow.

1878 – 1976 – George Hoyt whipple studied the rate of hemoglobin regeneration in dogs made

anaemic by venesection.

1885 – 1950 – George Richard Minot and William Murphy isolated the curative substance as

vitamin B 12. All three shared Nobel Prize in Medicine in 1934.

Causes of Megaloblastic Anemia:

1. Pernicious anemia – 80%

2. Post surgery – gastrectomy and Ileal resection

3. Bacterial overgrowth, parasitic infection

4. Drug therapy

5. Erythroleukemia

6. Hereditary disorders

Causes of Non Megaloblastic anemia: Macrocytosis usually asymptomatic but when associated

with anemia cause wide variety of symptoms.

1.Alcohol abuse and liver disease.

2. Hypothyroidism.

3. Reticulocytosis.

4. Aplastic anaemia

5. Paroxysmal nocturnal haemoglobinurea.

Current concepts: Megaloblastic anemia is always associated with folate and vitamin B 12

deficiency. Caused by slowing of DNA synthesis in all proliferating cells but most apparent in

rapidly growing cells such as haematopoietic precursors. RNA synthesis proceeds normally

leading to larger proportion of cytoplasm compared to the nucleus resulting in megaloblasts.

Etiology of impaired DNA synthesis is due to thymidylase synthetase deficiency because of low

folate and vitamin B12, which reduces tetrahydrofolic acid responsible for thymidylate

production.

Impact on Pregnancy: MA in pregnancy is usually secondary to folate deficiency. Diagnosed in

third trimester or postpartum period because of the adequate storage of folate for upto 20weeks,

which is utilized before anemia becomes apparent.

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Initially increased incidence of spontaneous abortion, abruption placenta and third trimester

bleeding has been reported. However other studies have failed to confirm these findings.

IUGR has been attributed to folate deficiency but is probably due to inadequate placentation.

Embryopathies such as neural tube defects are associated with folate deficiency and

supplementation with folic acid before and in early pregnancy reduces the incidence.

Preventive dose of Folic acid -- 5 mg / day 3 months before pregnancy

Supplementation dose of Folic acid – 4mg / day 3 months before pregnancy

Minimal requirements of vitamin B are necessary for adequate fetal development and serum B 12 12

levels are usually higher in infants than their mothers accounting for lack of significant

deleterious effects on fetus in mothers with PA. Some have described deficiency syndrome in

breast fed neonates of mothers with B deficiency characterized by failure to thrive, 12

developmental regression, and anemia apparent at 6 moments of age.

Sickle cell anemia

Sickle cell anemia is the first genetic disorder whose molecular basis was identified.

History: Known to the people of Africa for hundred of years.

1910 – James B Henick noted sickle shaped RBC in a patient from West Indies.

1922 – Vernon Mason named the disease as sickle cell disease.

1927 – Hahn and Gilespie showed sickling of RBC was related to low oxygen tension.

1940 – Sherman, a student from John Hopkins noted low oxygen altered the structure of

Hemoglobin.

1948 – Jenet Watson showed paucity of sickle cells in peripheral blood of newborn and stated that

it was due to fetal hemoglobin.

1956 – Vernon Ingram and J.A. Hurst sequenced sickle cell hemoglobin and identified glutamic

acid at position 6 was replaced by valine thus diagnosing the molecular basis of the disease.

1995 – Hydroxyurea the first and only drug proven to prevent complications of the disease was

reported by multicentric study.

1984 – The first bone marrow transplant in a child with sickle cell disease was reported and the

cure of the disease was published.

Current concepts: Sickle cell syndromes are autosomal recessive inherited disorders that result

from production of structurally abnormal â chain of adult hemoglobin molecule. Hemoglobin S

the defect occurs at 6th position of â chain where valine is substituted for glutamic acid.

Hemoglobin C lysine is substituted for glutamic acid at 6th position.

Impact on pregnancy: Exacerbations of disease.

Vaso occlusive crisis – more common.

More prone to pyelonephritis.

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Predisposes to symptomatic cholelitheasis and preeclampsia.

Increase in maternal and fetal mortality and morbidity.

Before 1970 fetal loss rate was 80% and maternal mortality was 30 – 40%

Today maternal mortality reduced to less than 1% with aggressive prenatal care, effective

management and intervention in pregnancy.

Hemolytic anemia

History: 1871 – Vanlair and Massius first described Hereditary Spherocytosis.

Current concepts: Hemolytic anemia ( HA) is characterized by an increased rate of erythrocyte

destruction. This premature destruction occurs due to 2 causes

1. Intrinsic defect – Inherited disorders and require molecular diagnosis.

a. Hereditary Spherocytosis – Inherited as autosomal dominant transfer and

occurs due to anomaly of RBC membrane.

b. Enzymatic defect –

i. Pyruvate Kinase Deficiency. Mutation involves structural gene coding for

L type pyruvate kinase.( Embden Meyerhoff pathway)

ii. G6PD deficiency – (Phosphate pathway). X linked disorder. Fully expressed in

heterozygous males. In females enzyme activity may be normal, moderately

reduced or deficient.

2. Acquired HA. :

a. Micro angiopathic hemolytic anemia. – Preeclampsia, HELLP syndrome, HUS.

b. Paroxysmal nocturnal haemoglobinuria.

c. Auto immune hemolytic anemia.

d. Physical agents – thermal injury, physical agents like prosthetic valves, drugs.

Impact on pregnancy: Hereditary spherocytosis in pregnancy is rare. Aplastic or hemolytic crisis

may be the first manifestation of the disease in pregnancy. Folic acid requirements are increased.

When fetus is affected with hereditary spherocytosis jaundice may be more prominent in

newborn, requiring exchange transfusion.

Pyruvate kinase deficiency – Limited data is available in literature but well tolerated in

pregnancy. In the fetus it can cause NON IMMUNE HYDROPS.

G6PD deficiency – Variable effects in pregnancy. Increased incidence of spontaneous abortion,

stillbirth, LBW, neonatal jaundice, and non immune hydrops are reported.

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Aplastic Anemia

Current concepts: Etiology is unknown in many cases. Rare and acquired disease usually due to

bone marrow failure secondary to physical, chemical, infectious insults, or nutritional deficiency.

Diagnosis depends on laboratory evaluation, bone marrow biopsy and peripheral blood

examination.

Introduction of bone marrow transplant as treatment in1969 by Thomas et all have changed the

life expectancy of these patients.30 years ago 1in 10 patients survived for 1 year and now 7 out of

10 survive and are restored to a quality of life.

Thalassemia in pregnancy

Current concepts: Thalassemia syndromes are inherited disorders that result from decreased

synthesis of â or á globin chain leading to reduced hemoglobin concentration.

Impact on pregnancy: Women with Thalassemia major both â and á rarely live to become

pregnant. Obstetric focus is prenatal diagnosis and recognition of carrier state in couples.

Prenatal diagnosis is possible by obtaining fetal cells for DNA analysis.

Replacement of blood and blood components in obstetrics.

Storage and transfusion of sterile compatible blood or blood constituents is a routine and life

saving procedure in obstetrics.

Key developments: 200AD – Reports of mystical qualities of blood is noted.

1667 - Richard Lower – reported first heterologous blood transfusion from lamb to an insane man.

1818- James Blundell initiated first human-to-human blood transfusion in acute hemorrhage due

to PPH.

1900 – Karl Landsteiner defined the blood groups and donor and recipient could be precisely

matched.

1914 – Hustin added citrate to prevent clotting.

1937 – First blood bank was established in Cook county hospital, U.S.A.

Bone marrow transfusion:

Century ago bone marrow was administered by mouth to patients with anemia and leukemia.

1950 – Early attempts were made with several transplants in France following radiation

accident.

1958 – Jean Dausset described human histocompatibility antigens.

1968 – First successful Bone marrow transplant was done at the university of Minnesota, U.S.A.

The recipient was a child with severe combined Immunodeficiency and the donor was a

sibling.

1973 – Physicians at Sloane Kettering cancer institute N.Y. performed unrelated bone marrow

20

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transplant in-patient with Combined Immune deficiency syndrome and after 7th time

engraftment was achieved and hematological function became normal

1970 – First patient with acute Leukemia was treated with unrelated bone marrow transplant

with success.

1980 – Various individual registries of HLA typed people were established.

1986 – national bone marrow donor registry began operations in U.S.A.

1990 – Dr. E. Donnall Thomas was awarded the Nobel Prize in Medicine for his pioneer work in

transplantation.

Today Bone marrow transplant is used in many hematological diseases notably in Leukemia and

Aplastic Anemia.

Stem cell therapy: Several types of stem cells have been discovered from germ cells, the embryo,

fetus, and adults. Each of these has the potential to revolutionaries the future of regenerative

Medicine in cell replacement therapy and to treat a variety of debilitating diseases. Stem cell is a

cell with the ability to divide indefinitely in culture and with the potential to give rise to mature

specialized cell types. Stem cells can be embryonic origin or adult stem cells found in diverse

tissues and organs. The best-studied adult stem cell is the haematopoietic stem cell ( HSC), which

have been used in clinical settings for over 40 years and form the basis of Bone marrow transplant

success. Umbilical cord blood contains a rich source of HSC that can be used to reconstitute the

blood system and can easily be extracted and cryopreserved, thus allowing HLA typed stem cell

banks to be established.

Marrow and Cord blood transplantation technology continue to evolve and has the potential

for use in Medical therapy of numerous life threatening diseases.

References:

Medline search

Clinical Obstetrics and Gynecology- September 1995, volume 38, number 3

Williams Obstetrics

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Foetal Anaemia

Dr. B.S.Rama Murthy MD DMRD DNB

Consultant Radiologist,

Srinivasa Ultrasound Scanning Centre Bangalore

Anaemia is defined as a pathological deficiency of the oxygen carrying component of blood

measured in unit volume concentration of Haemoglobin (Hb), red blood cell volume or red

blood cell number.

Foetal haemoglobin concentration increases with gestational age (GA). Hence the threshold Hb

concentration value below which foetal anaemia exists varies with gestational age. Multiples of

median enable us to express the level of Hb concentration below which foetal anaemia is

diagnosed.

Mari G and the group of sixteen others classified foetal anaemia as follows:

Mild anaemia – Hb conc. – 0.84 to 0.65 the median for GA

Moderate anaemia – Hb conc. – 0.65 to 0.55 median for GA

Severe anaemia – Hb conc. – less than 0.55 median for GA

Hydrops occurs when the Hb concentration falls below

5 gm/dl which corresponds to 0.46 times the median at 18 weeks and 0.36 times the median at 37

weeks.

Foetal anaemia is caused either by decreased production or increased destruction/loss of red

blood cells.

Decreased production: Congenital eg. Fanconi's pancytopenia, TAR syndrome, Diamond

Blackfan anaemia congenital dyserythropoietic anaemia etc. (marrow hypoplasia syndromes).

Mild anemia

Moderate anemia

Severe anemia

16 18 20 22 24 26 28 30 32 34 36

Gestational Age (Weeks)

1.16

0.84

Median

0.65

0.55

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

22

Page 23: Anemia Monograph

Acquired such as parvovirus B 19 infection.

Increased destruction/loss: Alloimmune anaemia (D, Kell, Kidd, ABO incompatibility),

foetomaternal haemorrhage, donor foetus in twin to twin transfusion sequence.

Haemoglobinopathies which affect the oxygen carrying capacity in the foetus may also be

considered. Alphao thalassemia (Bart's Hb) is an example and results in early foetal hydrops.

In anaemic fetuses the change in haematocrit results in a change in the blood viscosity and in turn

results in impaired release of oxygen to the tissues. Increased cardiac output and vasodilatation

are the main mechanisms by which the foetus attempts to keep metabolic equilibrium.

Diagnosis:

Obstetric history: Blood group and Rh type of mother and father, anti D administration in

previous pregnancies or abortions, previous issues with specific syndromes

It is the history that puts the process of foetal investigation underway. Sometimes ultrasound

detected foetal hydrops may set forth the process of investigation.

Maternal investigation: Relevant maternal investigations include Anti red cell antibody titre

(titres greater than 1 in 16 may prompt foetal testing however it should be pointed out that the

Indirect Coomb's test titres may not correlate with foetal haemoglobin levels), TORCH and

Parvovirus molecular or immunologic testing, Kleihauer Betke testing to recognize and

quantitate foetomaternal haemorrhage.

Foetal non invasive investigation: Ultrasonography:

Includes grey scale and doppler imaging

Grey scale imaging:

= Foetal hepatosplenomegaly reflects extramedullary erythropoiesis. Spleen length

and perimeter nomograms help us in objectifying the diagnosis.

= Small bowel serosal definition reflects presence of very early ascites.

= Bobbing cord sign reflects hyperdynamic circulation.

= Hydrops foetalis – end result of severe anaemia is severe tissue hypoxia / acidemia,

cardiac failure and decreased plasma oncotic pressure.

= Placental thickening, polyhydramnios,

Doppler imaging:

Decreasing Hb levels are associated with rising velocities in foetal circulation. This relation has

been proved in several series. High cardiac output and reduced blood viscosity are the factors

which result in hyperdynamic vascular flow states. Initially intrahepatic umbilical vein and

ductus venosus velocities were studied. We now have a large body of convincing evidence

showing that decreasing Hb concentrations are linearly related to increasing MCA peak systolic

velocities (PSV). MCA has been the chosen vessel because of the ease with which it can be

demonstrated by colour doppler. It's orientation enables one to achieve 0o or as close to 0o

23

Page 24: Anemia Monograph

doppler angle easily. The point of sampling is just beyond its origin from the internal carotid

artery in the plane of circle of Willis. The mapping is done with colour flow. Spectral doppler is

run for a few seconds only. The interobserver and intraobserver variability is low. Serial MCA

PSV measurements are at weekly intervals beginning from 20 to 22 weeks gestational age. All

fetuses with moderate or severe anaemia have PSV's above the 1.5 MoM's (multiples of median)

for gestational age. When this level of MCA PSV is reached invasive diagnosis and therapy is

planned (cordocentesis and intrauterine transfusion). Foetuses with below 1.5 MoM's MCA PSV

have no anaemia or mild anaemia (which anyway does not need transfusion). The 1.5 MoM cut

off has a sensitivity of 88% and specificity of 87% for moderate to severe anaemia. With the

advent of MCA PSV surveillance amniotic fluid spectrophotometry is almost totally given up.

Amniocentesis and Liley curve has a sensitivity of 76%.

The correlation between foetal Hct and MCA PSV is excellent not only for alloimmune anaemia

but also for anaemia due to other causes. MCA PSV surveillance has made it possible to avoid

70% of invasive procedures.

Furthermore the MCA PSV drops when anaemia is corrected.

Foetal invasive investigation:

Amniocentesis: Spectrophotometry (OD change at 450 nm)

Foetal blood sampling: Hb%, Reticulocyte count, Hct, Blood group and Rh type, Direct Coomb's

test, Bilirubin levels.

Therapy:

Congenital causes of marrow failure cannot be treated in the true sense of the term. Causes of

foetal anaemia due to acquired causes like alloimmunisation, Parvovirus infection or

foetomaternal haemorrhage can be managed by intrauterine transfusion until sufficient foetal

16 18 20 22 24 26 28 30 32 34 36

Gestational Age (Weeks)

0

10

20

30

40

50

60

70

80

90

100

1.50 Multiples of the medianMedian

24

Page 25: Anemia Monograph

maturity is attained. Delivery and neonatal management is then planned.

Since intrauterine transfusion (intravenous or intraperitoneal) is the bedrock of treatment we

shall now go through a few relevant details. Foetal transfusion is needed in only 10% of at risk

fetuses (Rh incompatibility) for severe anaemia before 34 weeks, the remaining 90% have mild or

no anaemia and can be managed with MCA PSV surveillance. With widespread usage of anti D,

the incidence of moderate and severe foetal anaemia has fallen. Even so alloimmune anaemia

due to Rh incompatibility is still the single largest cause.

Counselling: The parents should be counseled regarding the process of treatment, the number of

sittings that may be needed and the need for weekly monitoring of MCA PSV post procedure.

The possible complications during foetal transfusions should be highlighted. Informed consent

is taken.

Indication: Moderate / severe foetal anaemia as defined by the nomogram referred to above.

Foetal hydrops has lower salvage rates.

Preparation: The probe is sterile draped, the abdomen is surgically prepared and draped. No

maternal premedication is needed. Tocolysis and antibiotics are started on the morning of the

transfusion.

Site of foetal access: The cord insertion into the placenta is affords good access both for blood

sampling as well as transfusion. The intrahepatic umbilical vein may be used if the foetus is

dorsoposterior and the placental insertion site of the cord is difficult to access.

Foetal Hb concentration is estimated while the needle is in situ and if anaemia is moderate or

severe transfusion is done via the same needle. The pretransfusion foetal blood sample is also

subjected to Hct, reticulocyte count, direct Coomb's test and bilirubin estimation.

Donor unit: O-ve, packed red cells with a haematocrit of at least 85%, washed and irradiated (100

ml). Cross matching with maternal blood is recommended.

Foetal paralysis: Is achieved by Pancuronium 0.25 mg/kg estimated foetal weight injected IM

into the foetal thigh.

Volume transfused: Is computed using the donor haematocrit, foetal haematocrit and the

foetoplacental blood volume for gestational age. Aliquots of 10 ml are injected into the umbilical

vein through the needle coupled to a three way.

Continuous turbulence is observed in the umbilical vein during the intravenous injection. A

check is maintained on the foetal heart rate.

At the end of transfusing the desired volume a post procedure foetal blood sample is obtained

before withdrawing the needle. Hb, and HCt are obtained.

20 to 30 ml of the donor unit is also transfused into the foetal peritoneum at the end of the

intravenous transfusion.

Post procedure : Foetal MCA PSV is recorded to demonstrate a drop in velocities. Weekly MCA

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Page 26: Anemia Monograph

PSV surveillance is done and the subsequent transfusion is planned when the MCA PSV again

reaches beyond 1.5 MoM's. This generally occurs about 2 to 3 weeks after a sitting.

Complications: Cord haematoma, foetal exanguination and bradycardia are the complications,

Serial transfusions are done until the gestational age is 34 weeks after which delivery is planned.

Foetal transfusion is not only done for alloimmune anaemia but also for parvovirus B 19 and

foetomaternal haemorrhage as well. The term 'tide over transfusion' is used in these situations.

Thus we see that the causes of foetal anaemia are protean. Recognition of foetal anaemia is based

on history, maternal and foetal investigations. Foetal transfusions have revolutionized the

therapeutic scene.

References:

1. Mari G and the collaborative group for diagnosis of fetal anemia with Doppler

ultrasonography. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due

to maternal red-cell alloimmunization. N Engl J Med 2000;342:9–14.1.

2. Liley AW. Liquor amnii analysis in the management of pregnancy complicated by rhesus

sensitization. Am J Obstet Gynecol 1961;82:1359–70.

3. Nicolaides KH, Rodeck CH, Mibashan RS, Kemp JR. Have Liley charts outlived their

usefulness? Am J Obstet Gynecol 1986;155:90–4.

4. Fan FC, Chen RYZ, Schuessler GB, Chien S. Effects of hematocrit variations on regional

hemodynamics and oxygen transport in the dog. Am J Physiol 1984;238:H545–52.

5. Harman CR, Bowman JM, Manning FA, Menticoglou SM. Intrauterine transfusion --

intraperitoneal versus intravascular approach: a case-control comparison. Am J Obstet

Gynecol 1990;162:1053-1059.

6. Oepkes D, Seward PG, Vandenbussche FPHA, et al. Doppler ultrasonography versus

amniocentesis to predict fetal anemia. N Engl J Med 2006;354:156-164.

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Childhood Anemia

Dr. Christi Dominic Savio MD, DCH, Consultant Pediatrician,

Church of South India Hospital, Bangalore

Anemia is one of the commonest problems encountered in pediatric practice with nearly 70 1

million children below the age of 6 years in our country suffering from it. The vast majority of it is 2

due to the dietary deficiency of iron. This is surprising, given the fact that iron deficiency is

eminently amenable to prevention and treatment. What then is the reason for this high

prevalence in this day and age? Is it that we doctors are so busy treating other “more serious”

diseases that we forget or ignore this easily remediable condition? Or perhaps we ignore the fact

that Iron Deficiency Anemia (IDA) can and does take an enormous toll on the health of the

community including causing irreversible and permanent functional damage to the developing

brain. This article is an effort to sensitize us to what has been termed the Tragedy of Iron

Deficiency Anemia during infancy and early childhood.

PRACTICAL DEFINITION OF ANEMIA

The normal Hemoglobin varies with the age and sex of the individual and is given in Table 1

below. Anemia is said to be present when the level of Hemoglobin falls below these levels.

IRON DEFICIENCY AND IRON DEFICIENCY ANEMIA

Iron deficiency is the predominant nutritional deficiency that causes anemia all over the world.

According to the World Health Organization, iron deficiency is the most common and 5

widespread nutritional deficiency in the world.

Relation between Iron Deficiency and Iron Deficiency Anemia

Iron deficiency is defined as a condition in which there are no mobilizable iron stores and in

which signs of compromised supply of iron to tissues, including the erythron, are noted. It is only

TABLE 1: Normal Hemoglobin level

Population Group Normal Hemoglobin (grams per dL)

Adult Male

Adult Female (Non pregnant)

Adult Female (Pregnant)

Children 6 to 59 months of age

Children 5 to 11 years of age

Children 12 to 14 years of age

4Source: World Health Organization

13

12

11

11

11.5

12

27

Page 28: Anemia Monograph

when there is severe iron deficiency that anemia occurs. In

mild to moderate iron deficiency tissues are functionally

impaired though there is no anemia. It is important to realize

that iron deficiency causes impairment of cellular

functions even at levels that do not cause anemia

Prevalence of Iron Deficiency Anemia (IDA)

Iron deficiency is the only micronutrient deficiency that is

prevalent in significant numbers in both the developed and

the developing countries. WHO estimates that 2.1 billion 6

people globally are affected with anemia mainly because of iron deficiency. This is 30 percent of

the total world population!

1The prevalence of IDA in India based on various studies is as follows

However findings of the DLHS - RCH (District Level Household Survey under Reproductive and

Child health programme) jointly done by Ministry of Health and Family Welfare and 7

Department of Women and Child Development in 2002-2003 has put the figures of anemia

prevalence much higher as follows –

This is an alarming situation which is worsened by the fact that many among the health

profession are blissfully ignorant of the gravity of this problem!

TABLE 2: Prevalence of Anemia in various population groups

7TABLE 3: Prevalence of Anemia in various population groups (DLHS – RCH Report)

Total Population

Iron Deficiency

Iron Deficiency Anemia

Anemia

Venn Diagram showing relationship between Iron Deficiency and Anemia

Population Group

Infants and toddlers

Children 1 to 6 yrs

Adolescent girls

Non-pregnant women

65

60

88 (3.3% had severe anemia)

56.4

Pregnant women

Lactating women

74

85 (9.9% had severe anemia)

Prevalence (percentage)

Population Group

Children less than 5 years

Children 5 to 10 yrs

Teenagers 10 to 19 years

65

92

86

Prevalence (percentage)

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Groups at greatest risk for developing IDA are

v Children of all ages, particularly those between the ages of 6 months and 5years

v Preterm infants

v Women at the time of puberty, pregnancy and lactation

v The lower socioeconomic groups

v Non- meat eating groups

v Those with diseases like recurrent malaria, hook-worm infestation, and amebiasis.

Consequences of Iron Deficiency

It is vital for us to remember that anemia is only one of the consequences (although the most

visible one) of iron deficiency. Following are some of the important effects of iron deficiency.

1. Effects on the developing Central Nervous System (CNS)

This is one of the most disastrous consequences of Iron deficiency. Iron deficiency

results in impaired cognitive performance, diminished IQ, overall decrease in

scholastic performance and behavioral abnormalities including Attention Deficit

Disorder (ADD). The tragedy of this is that the deleterious effects of iron deficiency on

the cognitive performance in infancy and childhood are not correctable by subsequent 8-11

iron therapy. In other words the impairment in cognitive performance is

irreversible. Thus prevention of iron deficiency is the only way to prevent CNS

impairments.

2. Effects of Iron Deficiency on Scholastic Achievement in older children

Iron deficiency results in poor learning ability even among older children and

adolescents. Numerous studies have demonstrated poor learning scores in older

children and adolescents with iron deficiency including those with iron deficiency 12, 13

without anemia.

3. Compromised cardiovascular response to physical exercise

The cardiovascular response to physical exercise is compromised in children with

nutritional anemia even when it is mild and hence these children may never attain their 14

full potential in various school activities.

4. Impaired Immune Status

Iron deficiency causes increased mortality and morbidity from infections in all age

groups. This is because iron deficiency results in impaired intracellular killing in the

leucocytes, decreased ability of the lymphocytes to replicate and lowered concentration 15

of cells responsible for Cell Mediated Immunity. In one study in India it was found that

anemic children were 5.75 times more susceptible to Lower Respiratory Infections

compared with their non-anemic counterparts. The authors concluded that prevention 16

of anemia will reduce the incidence of LRTI.

29

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5. Suboptimal utilization of energy sources by the muscle cells.

Iron deficiency causes impaired work performance in adults and adolescents with even

mild iron deficiency without anemia.

6. Breath-holding Spells:

Iron deficiency is implicated in the causation of breath-holding spells in infants and

young children. Iron supplementation results in decrease in the frequency of breath-17-19

holding spells.

7. Increased risk of Febrile Seizures:

Studies show that children with iron deficiency have a greater chance of having febrile 20-22

seizures than their non iron-deficient counterparts.

8. Heart and Lung Disease:

Ischemic Heart Disease and symptoms of Chronic Lung Disease are worsened by iron

deficiency.

9. Cold Intolerance:

Chronic iron deficiency causes cold intolerance in one-fifths of the patients by interfering

with thyroxin and catecholamine metabolism. This may manifest as neuralgia, tingling

and numbness and vasomotor disturbances.

10. Increased heavy metal absorption:

Divalent metals like zinc and cadmium are absorbed excessively in the presence of iron 23, 24

deficiency leading to their toxicity.

11. Pseudotumour Cerebri:

Iron deficiency is one of the causes of this condition also known as Benign Intracranial

Hypertension.

12. Iron deficiency in Pregnancy:

Iron deficiency increases the maternal mortality and morbidity, perinatal mortality and

prematurity. Infants of iron deficient mothers develop anemia earlier and require more

iron than that available in breast-milk.

Iron Absorption

The absorption of iron from the gut depends upon various parameters of which the following are

of clinical importance having therapeutic implications

1. Forms of Iron

Iron is available as a) Heme and b) Non-heme forms. The latter in turn can be either

ferrous (divalent) or ferric (trivalent)

Heme iron is absorbed from the gut as intact metalloprotein and is not chelated by

dietary factors like phytin and tannins. It may thus appear to be the ideal form of iron for

supplementation. However, free heme in the gut rapidly polymerizes itself and becomes 30

Page 31: Anemia Monograph

unavailable for absorption. Therefore, free heme is not the ideal form of iron for

pharmacological use.

The ferrous and ferric forms of iron have different absorption pathways, namely the

Divalent metal transporter 1 (DMT1) pathway for the ferrous form and the Beta 3

Integrin and the Mobilferrin pathways for the ferric form.

2. Inhibitors of Iron Absorption

Many factors that are commonly found in the diet are potent inhibitors of iron

absorption. Some of the common inhibitors are phytates (present in cereals, legumes,

nuts and seeds), calcium (found in milk and milk products) and tannins (present in tea,

coffee and cocoa).

3. Enhancers of Iron Absorption.

Hemoglobin iron present in the meat and poultry, Vitamin C found in fruits, juices,

potatoes and vegetables such as green leaves, cauliflower and cabbage and condiments

such as Soya sauce enhance the absorption of iron several fold.

Knowledge of these modifiers of iron absorption is useful for the clinician who can make

appropriate adjustments in the patients' diet while on medicinal iron.

Diagnosis of Anemia

For practical purposes anemia is classified as mild when the hemoglobin is 10 and above,

moderate when it is between 7 and 9.9, severe when it is below 7 and very severe when it is below

4 (all values expressed as grams per dL).

1. Clinical examination

25-27.Clinical Examination is not very reliable for the diagnosis of anemia. Sensitivity of diagnosing

anemia is only 66 percent when the hemoglobin is in the range of 5 to 8 grams and 93 percent when

it is below 5 g / dL.25 Examination of palm for pallor is more reliable in children because of the 26

frequency of conjunctivitis in this age group.

2. Investigations

Since the clinical examination is not very reliable, investigations are essential to confirm and

quantify the anemia.

a. Hematological Tests

These are the basic tests required to diagnose anemia and include Hemoglobin

estimation, peripheral blood smear, and reticulocyte count. However, as already

mentioned, anemia is a rather late manifestation of iron deficiency and therefore other

tests are essential to diagnose iron deficiency in the early stages.

b. Tests to diagnose Iron deficiency:

The important tests that are used to diagnose iron deficiency are Serum Iron, Serum

Ferritin, Serum Transferrin (Total Iron Binding Capacity) and Serum Transferrin

31

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receptor level.

i. Serum Ferritin:

41This is the best single test for diagnosing iron deficiency . The only disadvantage is that

Ferritin is an acute phase reactant and therefore is elevated in chronic inflammatory

states. Thus, while a low serum ferritin level is diagnostic of iron deficiency a normal

level in the presence of chronic inflammation does not exclude iron deficiency. A level 2

less than 15 ìg per liter is diagnostic of iron deficiency.

ii. Serum Transferrin Receptor levels (sTfR)

This is a relatively new test and therefore not widely available. It is as sensitive as Serum 2,

Ferritin levels and it has the advantage of not being affected by chronic inflammation. 28-32

The normal range is 3-9 mg/L. In iron deficiency s TfR is elevated to above 9 mg/L

A practical and inexpensive method of diagnosing iron deficiency is to assess the

response to iron therapy. Iron deficiency is confirmed if the Hb rises by 1 g/dL or the

Hematocrit rises by 3% following a 4 week course of iron therapy in the dose of 3 33

mg/kg/day of elemental iron.

Another useful test to diagnose IDA in its early stages is the Red Cell Distribution Width

(RDW). This is an index of the variation of red cell size and can detect subtle degrees of

anisocytosis. Thus, elevated RDW is the earliest sign of IDA and is more sensitive than a 34

peripheral blood smear in the diagnosis of IDA. It is also more sensitive than serum

iron, ferritin or Total Iron Binding Capacity (TIBC). The normal range of RDW is 11.5 to

14.5

Treatment

Any underlying cause for the iron deficiency like occult bleeding, worm infestation should be identified and treated.

Iron therapyIron is available as various compounds. The compound of choice is ferrous sulfate because of its

42proven track record in terms of safety, efficacy and their low cost.

The dose is 6 mg of elemental iron per kilogram body weight per day. (WHO, however,

TABLE 4: Severity of Anemia

Severity

Mild

Moderate

Severe

10 and above

7 to 9.9

Below 7

Hemoglobin (g /dL)

Very Severe Below 4

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4recommends 3 mg instead of 6 mg ). Iron therapy should be continued for a few months after the hemoglobin has increased to acceptable levels in order to build up adequate stores in the body.

The percentage of elemental iron in various salts is given in the following table.

Newer Iron Preparations

Many newer forms of iron preparation are now available in the market with claims about their superiority. However none of these have been found to be superior to ferrous sulfate in terms of

42cost effectiveness. The following are some of the newer preparations.

a. Iron Hydroxide Polymaltose. This preparation made a huge splash when it was launched and it was claimed to be superior to the older preparations!35 But several studies both in India and abroad have concluded that this compound is inferior to Ferrous Sulfate. A few studies have even found it to be totally

36-38ineffective.

b. Carbonyl Iron. It is said to be very safe. Side effects are very minimal and the liquid preparation does not stain the teeth (The last mentioned may be a consideration particularly among children of the higher socioeconomic group). It is as effective as ferrous sulfate. The greatest advantage is its safety profile. Doses as high as 1000 to 10,000 mg have been tolerated without side effects in non-anemic and anemic adult volunteers and risk of iron poisoning in children

39,40can be eliminated by its use.

c. Sodium Iron EDTA. It is very safe and effective. It is not affected by the presence of iron absorption inhibitors like phytates and tannins in the diet. It is particularly

43, 44useful in food fortification.

d. Iron Ascorbate: Safe and effective.

As mentioned early an effort must be made to identify the cause of the iron deficiency such as helminthiasis, chronic malaria, and occult gastrointestinal bleeding like Meckel's Diverticulum and appropriate treatment instituted.

TABLE 5: Percentage of Elemental Iron in the commonly available preparations

Preparation

Anhydrous Ferrous Sulfate

Crystalline Ferrous Sulfate (7 H O)2

Ferrous Fumarate

Ferrous Gluconate

37

50

Ferrous Succinate

Colloidal Iron

12

Percentage of Elemental Iron

20

33

23

33

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Prevention of Iron Deficiency

Since the effects of iron deficiency, particularly those on the developing brain, in young children are irreversible it is vital that iron deficiency be prevented at all cost. Prevention of iron deficiency is fairly easy if the doctor is sensitized to the issue. The following are the groups that should be targeted for preventive measures.

* In communities where prevalence of iron deficiency is 40 percent or more 4

Tips for preventing IDA in infants and toddlers

v Encourage breast feeding for at least 1 year

v Use iron containing weaning food

v Do not use unmodified cow's milk for infants less under 1 year of age

v Encourage the use of iron rich vegetables like green leafy vegetables, beans, peas

v Promote use of meat wherever it is acceptable.

Eating practices that promote iron absorption from gut

v Do not drink coffee, tea at meal-time. Tea drinking to be postponed to 2 hours after meals

v Use milk, cheese and other dairy products as between-meal snack rather than at

mealtime.

Key Points

v Iron deficiency (ID) is a universal problem in children and women of child-bearing age.

v ID is a systemic disease and not merely a hematological disease.

v Impairment of cellular functions occurs in iron deficiency even when there is no anemia.

v ID can cause irreversible cognitive and learning disabilities with an overall reduction in

the IQ.

v All children and women in the reproductive age group require prophylactic low dose

medicinal iron to prevent iron deficiency.

4TABLE 5: Groups to be targeted for Iron supplementation to prevent IDA

Population group Dosage Schedule Duration of Supplementaion

Low Birth Weight Infants 2 to 23 months of age

2 mg / kg / day2 months to 23 months of age

Normal Infants 6 to 23 months of age *

2 mg / kg / day 6 months 23 months of age

Children 24 to 59 months of age * 2 mg / kg / day up to 30 mg 3 months

School Aged children * (above 60 months age)

Iron: 30 mg / dayFolic Acid: 250 :g / day

3 months

All women of child bearing age *

Iron: 60 mg / dayFolic Acid: 400 :g / day

3 months

Pregnant and Lactating Women As above Throughout pregnancy

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References

1. Deeksha Kapur et al. Nutritional Anemia and its Control. Indian J Pediatr 2002;69 (7):607-

616

2. WHO 1968. Nuritional Anemias: report of a WHO scientific Group, WHO, Geneva,

Switzerland).

3. George Buchanan. The tragedy of iron deficiency during infancy and early childhood. J

Pediatr 1999;135:413-5

4. Iron Deficiency Anemia – Assessment, Prevention and Control – A guide for program

managers. UNICEF, UNU, WHO 2001.

5. DeMaeyer EM, Adiels-Tegman M. The prevalence of anemia in the world. World Health Stat

Q 1985; 38:302-316.

6. Draper, A. (1997) Child development and iron deficiency. The Oxford Brief, pp.1–6. INACG

(International Nutritional Anemia Consultative Group), Washington,DC

7. Indian Medical Association 2006. http://www.imanational.com/Anaemia.htm#

8. Lozoff et al. Iron deficiency anemia and iron therapy effects on infant developmental test

performance. Pediatrics 1987; 79(6):981-95

9. Lozoff et al. Abnormal behavior and low developmental test scores in iron-deficient anemic

infants. J Dev Behav Pediatr 1985; 6(2):69-75

10. Walter T. Infancy: mental and motor development. Am J Clin Nutr. 1989;50(3 Suppl:655-61

11. Lozoff et al. Long-term developmental outcome of infants with iron deficiency. N Eng J Med.

1991;325(10):687-94

12. Halterman et al. Iron Deficiency and Cognitive Achievement among school-aged children

and adolescents. Pediatrics 2001;107:1381-1386

13. Sen and Kanani. Deleterious functional impact of anemia on young adolescent school girls.

Indian Pediatr 2006; 43(3):219-226

14. Mani et al. Cardiovascular Response in Anemia. Indian J of Pediatr 2005; 72:297-300

15. Mullick et al. Impact of iron deficiency anaemia on T lymphocytes & their subsets in children.

Indian J Med Res. 2006 Dec;124(6):647-54

16. Ramakrishnan and Harish. Hemoglobin level as a risk factor for LRTI. Indian J Pediatr 2006;

73 (10) : 881-883

17. Colina KF, Abelson HT. Resolution breathholding spells with treatment of concomitant

anemia. J Pediatr 1995; 126: 395-397.

18. Daoud AS et al. Effectiveness of iron therapy on breath-holding spells. J Pediatr 1997; 130:

547-550.

19. Bhatia MS, Singhal PK, Dhar NK, Nigam VR, Malik SC, Mu1lick ON. Breath-holding spells;

An analysis of 50 cases. Indian Pediatr 1990; 27: 1073-1079.

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20. Daoud et al. Iron status: A possible risk factor for the first febrile seizure. Epilepsia 2002;

43(7):740-743

21. Naveed ur Rehman et al. Association between iron deficiency anemia and febrile seizures. L

Coll Physicians Surg Pak 2005 Jun; 15(6):338-40

22. Pisacane et al. Iron deficiency anemia and febrile convulsions. BMJ 1996; 313:343

23. Goyer RA. Nutrition and metal toxicity. Am J Clin Nutr 1995 Mar;61(3 Suppl):646S-650S

24. Peraza MA et al. Effects of micronutrients on metal toxicity. Environ Health Perspect 1998

Feb;106 Suppl 1:203-216

25. Luby SP et al. Using clinical signs to diagnose anemia in African children. Bull World Health

Organ. 1995; 73(4):477-82

26. Zucker et al. Clinical signs for the recognition…. Bull World Health Organ. 1997; 75 Supple

1:97-102

27. Sdepanian VL. Diagnostic limitations…Rev Assoc Med Bras 1996; 42(3):169-74

28. Skikne et al. Serum transferring receptor: A quantitative measure of tissue iron deficiency.

Blood1990;75:1870-76

29. Cook JD. The measurement of serum transferring receptor. Am J Med Sci 1999

Oct;318(4):296-76

30. Lin XM et al. Levels of Serum transferring receptor. Br J Nutr 2006 Dec;96(6):1134-9

31. Drew & O'Shaughnessy. Recent Advances in hematology. BMJ 1999;318:991-994

32. Kogo Y et al. Circulating transferring receptor in human serum. Br J Hematology

1986;64:277- 81

33. Recommendations to prevent and control iron deficiency in the US. MMWR 1998 Apr 03; 47

(RR-3).

34. Vishwanath D et al. RDW in the diagnosis of IDA. Indian J Pediatr 2001 Dec; 68(12):1117-9

35. Langstaff RJ et al. Treatment of iron deficiency anemia: a lower incidence of adverse effects

with iron polymaltose complex than ferrous sulfate. Brit J Clin Res 1993; 4:191-198.

36. Mehta BC. Ineffectiveness of iron polymaltose in treatment of iron deficiency anemia. J Assoc

Physicians India 2003; 51: 419-421

37. Liu TC et al. Comparison of a combination ferrous fumarate product and a polysaccharide

iron complex as oral treatments of iron deficiency anemia: a Taiwanese study. Int J Hematol

2004 Dec;80(5):416-20

38. BC Mehta. Iron Hydroxide Polymaltose : Iatrogenic Cause of Persistent Iron Deficiency

Anaemia Despite Continuous Oral Iron Therapy; J Assoc Physicians India.

2002 Feb;50:279-80

39. Gordeuk et al. Carbonyl iron therapy for iron deficiency anemia. Blood.

1986 Mar;67(3):745-52)

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40. VR Gordeuk et al. High-dose carbonyl iron for iron deficiency anemia: a randomized double-

blind trial. American Journal of Clinical Nutrition; 46:1029-1034

41. Assessing the Iron Status of Populations. Report of Joint World Health Organization /

Centers for Disease Control and Prevention Technical Consultation on the assessment of Iron

Status at the population level. Geneva, Switzerland 2004. pp 16.

42. Technical Consultation on Strategies for prevention and control of iron deficiency anemia

amongst under three children in India. Indian Pediatrics 2002; 640-47.

43. Bothwell TH. Iron fortification with special reference to the role of iron EDTA. Arch

Latinoam Nutr 1999; 49(3 Suppl2):23S-33S

44. Huo J et al. Therapeutic effect of NaFeEDTA-fortified soy sauce in anemic children in China.

Asia Pac J Clin Nutr 2002; 11(2):123-7

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Anemia in Adolescents

Dr. Sheela V. ManeConsultant

Anugraha HospitalBhagwan Mahaveer Jain Hospital Bangalore

Adolescence is a significant period for physical growth and sexual maturation. Nutrition being

an important determinant of physical growth of adolescents, is an important area that needs

attention. More than two thirds of the adolescent girls suffer from anemia. Anemic adolescent

mothers are at a higher risk of miscarriages, maternal mortality and giving birth to stillborn and

underweight babies. Anemia in children and adolescents is often not a well appreciated and

recognized problem, but is an important impediment to physical and cognitive development.

The most common anemia in adolescents is that due to iron deficiency. 30-90% of adolescent

children in India are anemic depending upon socio-economic condition and whether they are

from rural or urban area. Basal requirement of iron during this period is 3mg/kg/day in female

taking into account both basal, and menstrual loss together. The cumulative effect of continuing

high iron needs and tendency of young women to eat less than men, probably explains why the

prevalence of I.D.A among females appears to increase through out adolescence. In females the

increase in the iron need is distributed over a longer period than in male. Girls have their growth

peak earlier than boys at mean age of 11.5 years of age with 95% from 9.7 to 13.3years. Tanner

stage 2 to 5 begins a year before peak growth and continues for a total of about 4 years, with

menstruation typically starting about 1 year after peak growth. There is a higher requirement of

iron for the female as compared to male during adolescent period and reproductive age period

due to blood loss during menstruation, pregnancy and lactation. Iron loss during menstruation is

estimated to be 16mg/kg/day.The overall iron requirement increases from a pre-adolescent level

of 0.7-0.9 mg/day, to as much as 2.2 mg/day or perhaps more in heavily menstruating young

women. The mean requirement for absorbed iron reaches to about 1.5mg/day at peak growth.

Hence adolescents girls are unlikely to acquire substantial iron stores during this period because

intake may average as little as 10-11 mg iron/day. The low iron store during this period in these

young women of reproductive age will make them susceptible to I.D.A during pregnancy

because dietary intake alone is insufficient in most cases to meet the requirement of pregnancy.

The importance of nutritious diet during this period in a woman's life cannot be overemphasized.

There are certain factors which contribute to dietary imbalances in this period.

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Factors influencing nutrition of adolescents

Common factors

1. Conditioning factors

v Infectious diseases are important factors responsible for malnutrition, particularly in

children and adolescents. Diarrhoea, intestinal parasites malaria and tuberculosis all

contribute to malnutrition.

v Poor environmental sanitation also leads to repeated bouts of infections.

v Girls lose a considerable amount of iron (average 1 mg daily) during menstruation.

Therefore, they require additional iron rich foods and supplements.

2. Cultural factors

v Food habits, customs, beliefs, traditions and attitudes.

v Religion

v Food fads

v Cooking practices

v Social customs

3. Socio-economic factors

Malnutrition and anemia are largely a by-product of poverty, ignorance, insufficient education,

lack of knowledge regarding nutritive value of foods, large family size, etc.

4. Gender issues

Girls and young women are discriminated against in both quantity and quality of food. On top of

this, they are married early and suffer early pregnancy and child birth further compromising

their nutritional status.

Factors specific to adolescents

Adolescents have a world of their own and have different eating patterns that influence their

nutrition. Adolescence is a period of emergence of an individual into a more independent phase

of life, which influences food behavior also. There is a lack of a sense of urgency regarding future

health. Family meals become less important. They tend to break away from family eating patterns

and succumb to unbalanced diets under influence of peers, mass media.

Personal self esteem and body image guide the eating behavior. Missing meals especially

breakfast is extremely common. SHAHN Survey-2002 among Delhi school students, reveals that

30% boys and 40% girls skip one meal everyday and breakfast is the commonest casualty (54%).

So how can one address this problem in the adolescents?

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Role at community level

Healthcare providers must educate the community to provide education on importance of

adolescent nutrition and influence the adverse socio-cultural practices.

Education regarding balanced diet for both boys and girls:

v provide education on the importance of nutrition for adolescents themselves and on

their offsprings

v promote good food selection and safe cooking practices

v promote concept of kitchen garden where green leafy vegetables etc. can be grown at a

very low cost

v create awareness in community to factors contributing to malnutrition and nutritional

anaemia, especially in girls.

v Involve other functionaries like AWW, schoolteachers, ASHAs to identify and tackle

nutritional problem.

v create awareness in community about role of malaria and hookworm infestation in

causing and aggravating anaemia

Role of individual counseling

Following tips can be used for counseling parents

v Food should be attractively served, with variety in colour, shape, size and texture.

v Likes and dislikes of the adolescent should be kept in mind

v Impress upon them that the growing bodies of the adolescents need balanced and

wholesome diet, missing meals is deleterious for health and breakfast is very important

for a good beginning of the day

v Snacks should be wholesome and nutritious

v Most of whole pulses should be included in diet

v Occasional consumption of ̀ junk food`may be allowed

v Highly fatty foods should be avoided

v Adolescent should be encouraged to exercise their choice and responsibility of foods

v The diets of girls need special emphasis on iron rich food, like leafy vegetables whole

gram cereals, dry fruit, egg, jaggery etc. The iron requirement is high because of

menstrual losses and growing phase.

Food fads, and anemia in adolescent children

Adolescents are more likely to skip meals at home,eat irregularly,make excessive use of less

nutritious snack food (junk foods). Young women often eat less than dictated by their appetite,

out of fear of obesity.

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Basic approach to prevention of IDA includes:

Education to increase dietary iron intake. Fortification of staple food with iron and introduction

of iron containing food in the diet

Control of infection, worm infestation.

Pharmacological iron supplementation.

Food fortification is one of the most effective ways of prevention of iron deficiency. Fortification

of suitable food vehicles with absorbable forms of iron is a highly desirable approach in

controlling iron deficiency.

Iron supplementation is essential for the rapid treatment of severe iron deficiency anemia as well

as for prophylaxis and prevention of anemia in both sex and age groups. Supplementation with

oral iron tablet or syrup is the most widely used approach to control global problem of iron

deficiency anemia.

Under adolescent girls' scheme, it is proposed to provide 100mg of elemental iron daily to all

adolescent girls every year for 100 days. Addition of 25mg of vit C to iron folate tablet has shown a

higher Hb response as compared to iron folate tablet alone in adolescent girls. The most common

form of iron in iron tablet is ferrous sulfate (20%iron) although fumarate (33%iron) and gluconate

(20%iron) are some times used. Based on a recent multicentric study in India it is now

recommended that adolescent girls on attaining menarche should be given weekly dosage of the

IFA tablet containing 100mg elemental iron and 500ug folic acid once a week accompanied by

appropriate dietary supplementation.

References :

ARSH WHO Module

Bhave's 'TEXT BOOK OF ADOLESCENT MEDICINE'

vUndernutrition in adolescence has long-term effects on their productivity

vMalnutrition in adolescence has serious implications with regard to predilection for degenerative diseases in adult life as well as for the health of next generation

vChronic energy deficiency and stunting is common but severe malnutrition is rare

vSubclinical micronutrient deficiencies are common because of increased requirements. Iron deficiency is the most common deficiency. Other common nutrient deficiencies include that of vit A, folic acid, iodine, zinc and calcium. Deficiency of iodine and folic acid in pregnant adolescent can cause irreparable damage to fetus.

vMalnutrition and micronutrient deficiencies are more common in poor socio-economic strata and among pregnant adolescents.

vPrinciples of management of severe malnutrition are similar to young children.

Key Points

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Bolt from the BlueAnemia due to Obstetric Hemorrhage

Dr. Prakash K. Mehta Chief, Division of Maternal Fetal Medicine

Bhagwan Mahaveer Jain HospitalAsha Pregnancy Care centre, Bangalore.

Introduction:Obstetric Hemorrhage is the most common cause of acute anemia as well as maternal death .It is

estimated that one woman dies every 4 minutes due to this catastrophe. In addition to death,

serious morbidity may follow hemorrhage. Sequelae include adult respiratory distress syndrome,

coagulopathy, shock, loss of fertility, and pituitary necrosis (Sheehan syndrome).

Causes:

Massive obstetric hemorrhage may be antepartum or postpartum

Antepartum Hemorrhage

Early Pregnancy: Causes of hemorrhage in early pregnancy may be abortion, ectopic or molar

pregnancy.

Late pregnancy: If bleeding occurs in later pregnancy or during labor but before delivery,

placenta previa, abruptio placentae or ruptured uterus have to be suspected

Placenta Previa : It occurs in one in every 200 pregnant women, most often in the third trimester.

The classic presentation of placenta previa is painless vaginal bleeding and a soft, non tender

uterus. All patients with placenta previa should be informed of the risk of severe PPH, including

the possible need for transfusion and hysterectomy. Blood may distend the uterus and prevent

effective contraction

Placenta accreta. This is a rare disorder, occurring in only 1 in 5000 pregnancies. 9 to 10% of cases

of placenta previa are associated with placenta accreta, an abnormally firm attachment of the

placenta to the wall of the uterus. This condition most commonly occurs in women who have had

previous uterine surgery. Placenta accreta prevents the placenta from separating from the uterine

wall at the time of delivery and can cause severe bleeding that often necessitates hysterectomy.

Placental abruption. Since ultrasound examination has a high false-negative rate in diagnosing

abruption, this obstetric complication is diagnosed clinically The management of abruptio

placentae is primarily supportive and entails both aggressive hydration and monitoring of

maternal and fetal well-being. Coagulation studies should be performed, and fibrinogen and D

dimer or fibrin degradation products should be measured to screen for disseminated

intravascular coagulation. Packed red blood cells should be typed and held. If the fetus appears

viable but compromised, urgent cesarean delivery should be considered.

Bleeding begets bleeding

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Uterine rupture. In women who have had a previous Caesarean birth, a disruption of the surgical

scar in the uterus is a rare but dangerous cause of vaginal bleeding, intense abdominal pain and

abdominal tenderness. The presentation of uterine rupture may be similar to that of abruptio

placentae. Treatment includes aggressive resuscitation and urgent surgical delivery.

Others: .Cervical varix during pregnancy is a rare condition. The conventional approach to

cervical varices during pregnancy is expectant management and bed rest. The placement of a

cerclage may result in absence of vaginal bleeding during pregnancy. Ectopic deciduosis is

usually no more than a pathologic curiosity. In a pregnant patient with spontaneous

intraperitoneal hemorrhage, however, it must be considered because it results in a high incidence

of maternal and neonatal mortality.

Postpartum Hemorrhage

The average blood loss at the time of delivery is approximately 500 ml during a vaginal delivery

and 1,000 ml during a cesarean section. Excessive blood loss or "postpartum hemorrhage"

complicates approximately 4% of vaginal deliveries and 6-7% of cesarean sections. Estimates of

blood loss at delivery are subjective and generally inaccurate. Studies have suggested that

caregivers consistently underestimate actual blood loss. Another consideration is the differing

capacities of individual patients to cope with blood loss. A healthy woman has a 30-50% increase

in blood volume in a normal singleton pregnancy and is much more tolerant of blood loss than a

woman who has preexisting anemia, an underlying cardiac condition, or a volume-contracted

condition secondary to dehydration or preeclampsia. Lack of experienced obstetricians, blood

transfusion services, anesthetic services, and operating capabilities also play a role for the less

favorable outcome of PPH.

Risk Factors include PPH in a previous pregnancy, retained placenta, failure to progress during

the second stage of labor, placenta accreta, lacerations, instrumental delivery, large for

gestational age, over distension of the uterus, hypertensive disorders and induction of labor and

augmentation of labor with oxytocin

Causes: The causes for PPH can be remembered by mnemonic “4 Ts”: tone, tissue, trauma, and

thrombosis (Society of Obstetricians and Gynecologists of Canada, 2002).

Tone: Uterine atony is the commonest cause for PPH and account for 90% of cases. Uterine atony

and failure of contraction and retraction of myometrial muscle fibers can lead to rapid and severe

hemorrhage and hypovolemic shock.

Tissue: The placenta is more likely to be retained at extreme preterm gestations (especially <24

wk), and significant bleeding can occur. Retention of a portion of the placenta is more common if

the placenta has developed with a succenturiate or accessory lobe. Failure of complete separation

of the placenta occurs in placenta accreta and its variants.

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Trauma: Damage to the genital tract may occur spontaneously or through manipulations used to

deliver the baby. Continuing hemorrhage in a patient with a firm uterine fundus may indicate a

hidden vaginal or cervical laceration. This type of injury is easier to identify and repair with

adequate lighting, exposure and assistance. Uterine rupture can occur with previous cesarean

delivery scars. Any uterus that has undergone a procedure resulting in a total or thick partial

disruption of the uterine wall should be considered at risk for rupture in a future pregnancy. This

includes myomectomy; uteroplasty for congenital abnormality; cornual or cervical ectopic

resection; and perforation of the uterus during dilatation, curettage, biopsy, hysteroscopy,

laparoscopy, or intrauterine contraceptive device placement. Trauma may occur following very

prolonged or vigorous labor, especially if the patient has relative or absolute cephalopelvic

disproportion and the uterus has been stimulated with oxytocin or prostaglandins Trauma also

may occur following extra uterine or intrauterine manipulation of the fetus. The highest risk is

probably associated with internal version and extraction of a second twin; however, uterine

rupture may also occur secondary to external version. Finally, trauma may result secondary to

attempts to remove a retained placenta manually or with instrumentation. While puerperal

hematomas typically cause a vulvar or vaginal mass, an occult retroperitoneal hematoma can

present with severe abdominal pain and shock after delivery. Visible hematomas that are less

than 4 cm in size and not expanding may be managed with ice packs and observation. Larger or

expanding hematomas must be incised, irrigated and packed, with ligation of any obvious

bleeding vessels

Thrombosis: If uterine exploration is non diagnostic and the fundus is firm, rarer causes of

hemorrhage should be considered. If venipuncture sites are oozing, coagulopathy should be

considered. Thrombocytopenia may be related to preexisting disease, such as idiopathic

thrombocytopenic purpura, or acquired secondary to HELLP syndrome (hemolysis, elevated

liver enzymes, and low platelet count), abruptio placentae, disseminated intravascular

coagulation (DIC), or sepsis. Rarely, functional abnormalities of platelets may also occur. Most of

these are preexisting, although sometimes previously undiagnosed. . Finally, dilutional

coagulopathy may occur following massive PPH and resuscitation with crystalloid and packed

red blood cells (PRBCs).

Management:

General:

v Accurate estimation of blood loss

v Prompt recognition and treatment of clotting disorders

v Multidisciplinary approach

v Use of adequately sized intravenous cannula

v Importance of monitoring central venous pressure.

v Arrangement of adequate quantity of blood

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Protocol :

v Assessment - Gathering information

v Diagnosis - Interpreting the information

v Planning - Developing the care plan

v Intervention - Implementing the care plan

v Evaluation - Evaluating the care plan

As with any emergency, the assessment of obstetric hemorrhage begins with the ABCs (airway,

breathing and circulation). A delay in the correction of hypovolemia, diagnosis and treatment of

defective coagulation and/or surgical control of bleeding are the avoidable factors in most

maternal deaths caused by hemorrhage. The main goal is to maintain effective circulating

intravascular volume by prompt and adequate replacement of blood, crystalloids or fresh-frozen

plasma through more than one intravenous line (it might be necessary to pump blood under

pressure) with constant monitoring of the pulse rate and the arterial blood pressure. The rapid

correction of hypovolemia with crystalloids and red cells is the first priority, followed by blood

component therapy.

Lab Studies:

Once the diagnosis of PPH has been made, a CBC and baseline coagulation studies should be

performed.

Initially, the hemoglobin value does not reflect the amount of blood loss. Initial coagulation study

findings are usually within reference ranges; however, abnormalities may be noted. This is most

common when PPH is preceded by abruptio placenta, HELLP syndrome, and fatty liver of

pregnancy, intrauterine fetal demise, embolic events, or septicemia.

If the International Normalized Ratio and/or activated partial thromboplastin time are elevated,

the use of fibrinogen, a thrombin time measurement, D-dimers, and a blood film should be

considered. In late pregnancy, fibrinogen levels are 2-3 times the upper reference range limit in

the nonpregnant state, and a level within the nonpregnant reference range should be viewed with

caution if the clinical picture suggests coagulopathy.

Imaging Studies: The onset of PPH is generally rapid. With proper diagnosis and treatment,

resolution usually occurs before further laboratory work or imaging can be undertaken. In

experienced hands, bedside ultrasound may help reveal clots or retained products; however, the

treatment of PPH includes manual exploration if bleeding persists. This renders ultrasound

redundant in the acute setting at a time when treatment must not be delayed. Antenatal

ultrasound is indispensable for detecting high-risk patients with predisposing factors for PPH,

Continuous slow bleeding or sudden bleeding is an emergency Intervene early & aggressively

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such as placenta previa, and is becoming increasingly sensitive and specific in the diagnosis of

placenta accreta and its variants

Treatment : When uterine atony is the cause of postpartum hemorrhage, treatment is fundal

massage and uterotonics which could be 10 U of oxytocin in 500 mL of intravenous fluid by

continuous drip, 200-250 mcg of ergonovine intramuscularly, or 250 mcg of 15-methyl

prostaglandin F2-alpha intramuscularly.. Modern management of atonic PPH entails the use of

prostaglandins administered parenterally, orally, rectally, or vaginally. Each has advantages and

disadvantages in terms of efficiency, availability, cost, stability, and ease of administration. The

use of misoprostol and a long-acting oxytocin analogue (carbetocin) is being studied for this use

If the placenta has been delivered, inspection findings suggest whether portions of it have been

retained. If it is undelivered or if retained clots or placental fragments are distending the uterus

and bleeding is persisting despite appropriate ongoing treatment, manual exploration and

removal should be undertaken. This is simultaneously therapeutic by emptying the uterus and

permitting contraction while also aiding in the diagnosis of placenta accreta and uterine rupture.

Cervical and vaginal lacerations may also be palpated at this time.

In addition to the appropriate use of oxytocic agents for uterine atony, surgical techniques,

including uterine tamponade, major vessel ligation, compression sutures, and hysterectomy,

may be required. All gynecologists should be able to perform without delay the operative

maneuvers which are necessary to control the bleeding, including hypogastric artery ligation, or

even emergency hysterectomy. Bimanual compression, uterine packing, and such surgical

interventions as B-Lynch suture, ligation of uterine artery, ovarian artery, and internal iliac artery,

and embolization are effective methods for controlling intractable hemorrhage.

Uterine Tamponade: Attempting to compress the uterine sinuses and to stop bleeding via uterine

packing is a reasonable option for management of PPH. A good packing technique entails careful

layering of the ribbon gauze pack to occlude the whole space of the uterine cavity, which is much

easier in theory than in practice. Sengstaken-Blakemore tube and a Rusch urologic hydrostatic

balloon catheter have been used for this purpose. An inexpensive and easily available alternative

is to use an inflated condom as a tamponade. With aseptic precautions, a sterile rubber catheter

fitted with a condom is introduced into the uterus. The condom is inflated with 250-500 mL

normal saline according to need.

The condom catheter was kept for 24-48 hours, depending upon the initial intensity of blood loss,

and gradually deflated when bleeding ceased

Ligation techniques: Ligation of the uterine arteries, ovarian arteries and hypogastric arteries

will usually control uterine bleeding and arterial embolization is also effective. Uterine artery

ligation. When medical management fails, this is a highly effective option. Uterine artery ligation

can be effective in 93% of cases, with a 2.2% complication rate. It's a fast procedure, too, taking

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perhaps 5 minutes for both sides. No. 1 chromic resorbable suture can be used to tie at the level of

the internal os and includes 2-3 cm of myometrium. Ligation of the hypogastric arteries: Specific

information regarding its effectiveness is lacking. In a study this procedure was effective in

controlling bleeding in eight of 19 patients (42%). In these patients, blood loss, operating time,

and intraoperative morbidity was increased when compared with a group of patients

undergoing emergency hysterectomy for obstetric hemorrhage without prior ligation of the

hypogastric arteries, There was also a 10 fold higher urologic injury rate. Ligation of the uterine

arteries or hypogastric arteries may be performed; both operations require laparotomies.

Bilateral hypogastric artery ligation has a success rate ranging from 40 to 100%.In contrast;

uterine artery ligation has been shown to have a success rate of 92% and a complication rate of 1%.

Both these techniques aim to leave the uterus intact and preserve fertility.

Postpartum hemorrhage that cannot be controlled by local measures has traditionally been

managed by bilateral uterine artery or hypogastric artery ligation. These techniques have a high

failure rate, often resulting in hysterectomy. In contrast, endovascular embolization techniques

have a success rate of >90%.Placement and utilization of arterial catheters for uterine artery

embolization is becoming more widespread and new surgical technology such as the argon beam

coagulator seems promising.

Hysterectomy should also be considered in severe cases. A reluctance to proceed with

hysterectomy for obstetric hemorrhage may be a more likely cause of preventable death in

obstetrics than a lack of surgical or medical skills.

Others: The non-pneumatic anti-shock garment (NASG) exerts lower body counter pressure as a

means of returning blood to the central circulation and it tamponades the abdomen and pelvis to

decrease further bleeding

Recombinant factor VIIa (40-90 mcg/kg, a clotting factor used for hemorrhage in patients with

factor deficiencies undergoing testing for hemorrhage from several other sources including

variceal and obstetric) has been reportedly dramatically effective in several case reports and a

case series for PPH refractory to oxytocin.

Data Analysis : The Division of Maternal Fetal Medicine at Bhagwan Mahaveer Jain Hospital is a

referral centre for high risk pregnancies. During the years 2005 -06, there were 41 patients with

massive obstetric hemorrhage requiring intensive care. 9 patients were referred with APH of

which 2 patients with massive DIC and ARF died. 3 of these patients had PPH also. There were 35

patients with postpartum hemorrhage requiring intensive care, of which 4 died. Atonic PPH was

present in 7 patients, while the rest were with background of DIC, HELLP or adherent placenta.

DIC associated with massive hemorrhage was identified in 18 patients .HELLP syndrome

worsening the bleeding was present in 21 patients. Four of the patients had infective hepatitis

leading to PPH while AFNL was identified in 3 patients. Majority of the patients had multiple

associated factors leading to hemorrhage with HELLP and PIH being the commonest. HELLP

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was unidentified in 10 of the patients. Identification of this disorder and investigations including

hematocrit, platelet count and liver enzymes could have possible led to early intervention and

prevented these catastrophes. Obstetric hysterectomy was required for 6 patients. 3

hysterectomies were done for placenta previa accreta , 2 were for atonic PPH with DIC and one for

rupture uterus. Arterial embolization was considered for 3 patients but either because of

associated factors like massive DIC or constraint of time, alternative management methods were

used. Uterine tamponade with roller gauze packing was done in 11 patients .Packing was done

post C. section in 7 patients. 2 patients had to be packed following vaginal delivery. 2 patients

who continued to bleed even after Ob hysterectomy settled down with packing.. Massive

transfusion was required for 30 patients. Majority of these patients were referred in shock or after

the onset of DIC. Awareness, suspicion and early referral can reduce the morbidity and avert

mortality.

Conclusion:

Life-threatening hemorrhage requiring immediate treatment affects only 1 in 1000 deliveries. It

will therefore occur about four times a year in a large maternity hospital. This is infrequent

enough to make practice drills necessary. With so many treatment options, ultimately the choice

of technique becomes one of individual preference, institutional availability and the individual

clinical scenario. Timely hysterectomy should be performed for signs of refractory bleeding.

Application of medical and surgical principles combined with recent technologic advances will

help the obstetrician avoid disastrous outcomes for both mother and fetus.

Blood Volume Loss

500 -1000 (10 - 15%)

Blood Pressure (systolic)

Symptoms and Signs

Degree of Shock

NormalPalpitations, tachycardia, dizziness

Compensated

1000 -1500 mL (15 - 25%)

Slight fall (80-100 mm Hg)

Weakness, tachycardia, sweating Mild

1500 -2000 (25-35%)

Moderate fall (70-80 mm Hg)

Restlessness, pallor, oliguria Moderate

2000-3000 mL(35-50%)

Marked fall (50-70 mm Hg)

Collapse, air hunger, anuria Severe

Blood loss and effects

Accidental hemorrhage Uterine rupture

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Adapted from Int J Gynaecol Obstet 1997 May; 57(2): 219-26

Antepartum Vaginal Bleeding

Massive Bleeding

Call for help

Evaluate ABCs (airway, breathing, circulation)

Administer intravenous fluids

Administer supplemental oxygen

Consider transfusion

Consider urgent cesarean delivery

History and physical examination

Fetal monitoring

Normal“bloodyshow”

Severely distressedfetus (especially ifthe bleeding beganabruptly with therupture of membranes)

Uterine pain? Inflamed cervix ormucopurulent

discharge

Routineevaluation

No pain or painonly with

contractions;nontender fundus

Pain betweencontractions ortender fundus

Probable cervicalinfection

Culture and treatas appropriate

Consider uterinerupture (especially

if fundus isexpanding)

Consider abruptioplacenta

Monitor fetusand mother

supportive care

Suspect placentaprevia

Suspect vasaprevia

Immediateultrasound

examination ifavailable

Distressed fetus Death of fetus

Consider urgentcesarean delivery

Vaginal deliveryCesarean deliveryif in labor

Urgent cesarean delivery

Consider urgentlaparotomy

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Postpartum hemorrhage

Abdominal pain and shock withour

vaginal bleeding(rare)

Oozing fromvenipuncture

sites(rare)

Massive bleeding

Consultation for possible

retroperitonealhematoma

Consider coagulopathyCoagulation studies

Call for help

Evaluate ABCs (airway, breathing, circulation)Administer intravenous fluids

Administer supplemental oxygen

Consider transfusion

Placenta delivered?

No Yes

Manual exploration of uterus Vigorous fundal massageOxytocin, 10 to 30 units administeredrapidly in 1L of intravenous saline

Indistinctcleavage plane

Distinctcleavage plane

Considerplacenta accreta

Manualextraction of

placenta

Firm fundus, still bleeding Soft fundus, still bleeding

Explore for cervical,vaginal or vulvar lesions

Consultation forprobable urgenthysterectomy

Bimanualcompression of

uterus while awaiting help

Vaginal or vulvar hematoma

Vaginal or cervical laceration

No lesions Presumed uterine atony

Continued fundal massageMethylergonovine(Methergine),0.2 mg given intramuscularly(if the the patient does not havehypertension)orCarboprost(Hemabate)250 :g intramuscularly

Manualexploration of uterusRepair

4 cm or largerand expanding

Incise, drain andpack

Up to 4 cmand stable

Ice packs,observe

Retained placentaor clots

Uterine rurpture Uterine inversion Nothing found

Seek consultationRepeat algorithm

ResuscitationReplace uterus

ResuscitationUrgent laparotomy

Remove

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Bibliography:

1. Alvarez M, Lockwood CJ, Ghidini A: Prophylactic and emergent arterial catheterization for

selective embolization in obstetric hemorrhage. Am J Perinatol 1992 Sep-Nov; 9(5-6): 441-4

2. Bobrowski RA, Jones TB: A thrombogenic uterine pack for postpartum hemorrhage. Obstet

Gynecol 1995 May; 85(5 Pt 2): 836-7.3. Haynes J: Use of recombinant activated factor VII in massive obstetric hemorrhage Int J Obstet

Anesth. 2007 Jan; 16(1):40-49.

4. Dildy GA: Postpartum hemorrhage: new management options. Clin Obstet Gynecol 2002 Jun;

45(2): 330-44

5. Wittich AC, Salminen ER, Hardin EL: Uterine packing in the combined management of

obstetrical hemorrhage. Mil Med 1996 Mar; 161(3): 180-2

6. Hayman RG, Arulkumaran S, Steer PJ. Uterine compression sutures: surgical management of

postpartum hemorrhage. Obstetric Gynecol 2002; 99: 502–6

7. Mason BA. Postpartum haemorrhage and arterial embolization. Curr Opin Obstet Gynecol

1998; 11: 475–9

8. Rizvi F, Mackey R, Barrett T, McKenna P, Geary M, Successful reduction of massive

postpartum hemorrhage by use of guidelines and staff education, BJOJ2004 May;111(5):495-8.

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OFF COLOUR AFTER FORTY

DR. DEVIKA GUNASHEELA, MRCOG (Lond.),

Fellow of Reproductive Medicine (RGUHS)

Anaemia is one of the most widespread and often neglected disorders. It is the bane of

most underdeveloped countries of the world, and a curse of Indian womanhood. WHO

estimates are that two billion people in the world are anaemic, accounting for 30 % of the

world's population. Anaemia affects 13 % of the population in the developed world and

44 % in the developing world. Amongst the Asian countries, perhaps Bangladesh and

China have a higher incidence of anaemia than India, but Pakistan, Nepal and Sri Lanka

have a lower incidence than India. Whereas the incidence of anaemia ranges between 20

and 30 % in the middle income groups, it is much higher in the lower income groups – 60

% (urban women) and 70 % (rural women). In geographical areas where malaria and

helminthic diseases are endemic, the incidence of anaemia rises to almost 90 %. Anaemia

is three times more prevalent in southern Asian women than in European women. It was

found that anaemia was less prevalent after the menopause in European women but

remained common after the menopause among Indian and Bangladeshi women.

The menopausal transition is continuous and not a snapshot in time. In the absence of

disease, this process involves changes and irregularity of both bleeding and hormone

levels. Irregular bleeding that arises during this period is often subject to medical and

surgical investigations and treatment even though the parameters of what are abnormal

are not well established.

Perimenopause or the recently preferred term The Menopausal Transition (MT) is defined

by the WHO as the period in time beginning 2 – 8 years prior to the Final Menstrual 1

Period (FMP) and lasting upto 12 months after the FMP.

Abnormal uterine bleeding is one of the most common complaints during the 2

perimenopausal transition as cycles become more irregular. It has been estimated that

menstrual irregularity occurs in more than half of all women. Bleeding can be irregular, 3

heavy or prolonged. The differential diagnosis during these years is vast, as anatomic

hormonal, and metaplastic processes have a higher incidence : anovulatory bleeding,

uterine leiomyoma, endometrial polyps, adenomyosis, endometrial hyperplasia or

endometrial carcinoma. Anovulation and uterine fibroids are the most common hormonal

and anatomic causes of abnormal uterine bleeding in the late reproductive age.

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The subjective self – assessment of uterine bleeding is not at all reliable. 40 % of women

with more than 80 ml of objectively quantified menstrual blood loss (an amount that is

significantly associated with development of anaemia) described their bleeding patterns as

only moderately heavy, whereas 14 % with only 20 ml or less of bleeding found this to be

heavy. Only 60 % of women complaining of menorrhagia actually experienced more than 4

80 ml of menstrual blood loss.

HORMONAL THEORIES :

Many theories have been put forward to explain the hormonal mechanisms responsible

for the vagaries of perimenopausal bleeding. Ample oestrogen levels and prolonged

endometrial stimulation in longer anovulatory cycles may well contribute to the rising

incidence of endometrial hyperplasia and dysfunctional uterine bleeding as women 5

transverse the MT.

ANATOMICAL CAUSES :

Leiomyomata and polyps are common in women over the age of 35 and are accepted

cause of abnormal uterine bleeding. Uterine fibroids have a prevalence rate of about

25% over the general population. Though rarely malignant, leiomyomata have always been

a major contributor to abnormal bleeding or pain and remain the most common diagnosis

associated with hysterectomy. Submucous fibroids seem to have a greater effect on

bleeding patterns than intramural fibroids but both lead to heavy and prolonged bleeding.

DIAGNOSTIC WORKUP :

All complaints of irregularity in bleeding patterns may not warrant investigations. But

prolonged bleeding (lasting more than 10 days) or intermenstrual (non-cyclical) bleeding 6

are not considered normal and deserve workup. Although polyps and fibroids are the

most common anatomical concern one should not overlook the possibility of endometrial

carcinoma in the aging female. The incidence of endometrial carcinoma increases with age

from 30 – 39 year old women with the rate of 2.3 / 100,000 women and in the 1

perimenopausal age group (40 – 49 year old) a further increase to 6.2 / 100,000 women.

The importance of endometrial biopsy cannot be over emphasized for women with

abnormal uterine bleeding during the menopausal transition and also after menopause.

The diagnostic approach to a woman with abnormal perimenopausal bleeding has evolved

over the last century from operating room curettage to outpatient vacuum suction

curettage to eventually the Pipelle plastic catheter. Proponents of the Pipelle catheter cite

that it is relatively comfortable for patients. It is reported to have a sensitivity as high as

97.5 % in detecting endometrial carcinoma, but these biopsies were done on woman with 7

known pathology. Of the patients who have had false negative finding by Pipelle

sampling, the disease was either confined to a polyp or comprised less than 5 % of cavity

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surface area and therefore was missed.

The noninvasive relatively inexpensive and highly reproducible nature of transvaginal

ultrasound makes it an especially attractive assessment tool to exclude uterine

abnormalities. Significant progress has been made in the evaluation of perimenopausal

women using saline infusion hysterosonography (HSN) to help assess the endometrial 8

cavity for focal lesions.

HYSTEROSCOPY :

Another evaluation that may be helpful in selected cases is hysteroscopy. This allows the

identification of endometrial polyps or submucosal fibroids.

Goldstein1 has presented an algorithm that utilizes trans vaginal ultrasonography and

provides a stepwise approach to working up the perimenopausal patient with abnormal

uterine bleeding. If the baseline ultrasound shows a thin distinct endometrial stripe less

than or equal to 5 mm in width, a diagnosis of dysfunctional uterine bleeding can be

safely made. If the endometrial stripe is thickened to greater than 5 mm or it is difficult to

ascertain the endometrial echo, an HSN is warranted for a uterine evaluation. Based on

the HSN results, a diagnosis of dysfunctional uterine bleeding can be made, an office

endometrial biopsy may need to be taken, or a hysteroscopy with resectoscopic biopsy is

performed for final diagnosis and / or therapy.

MEDICAL MANAGEMENT :

Medical treatment of perimenopausal abnormal uterine bleeding is either hormonal or

surgical depending on the patient's symptoms and diagnosis. As anovulatory bleeding is

one of the most common causes, hormonal therapy is the first approach after intra uterine

pathology has been excluded.

NSAIDs :

These are thought to be menstrual blood loss through the inhibition of endometrial

prostaglandins (PGE2 alpha and PGF2 alpha). Mefanamic acid, Tranexamic acid have been

used with varying degree of success.

HORMONES :

Although progesterone only or estrogen progestin combination treatment of irregular or

dysfunctional bleeding is common, no randomized controlled trials to demonstrate their

efficacy in this setting exist. Progestin only regimens such as medroxyprogesterone acetate

(MPA) have been shown to reduce both the amount and duration of uterine bleeding in

anovulatory women. Specifically, MPA 10 mg per day for 10 to 14 days every month is 9

effective in controlling unpredictable anovulatory bleeding. Progestins are able to induce a

secretory transformation in otherwise estrogen – stimulated proliferative endometrium, and

they are effective in allowing a withdrawal bleed for women with thickened endometrial

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10linings that are commonly seen in anovulation.

Oral Contraceptives in low – risk premenopausal women with hormone – related symptoms

who are not using any form of contraception, modern low – dose (<35 µg ethinyl estradiol)

oral contraceptives offer many advantages with minimal risk (59). New formulations

contain as little as 20 µg of ethinyl estradiol and 1 mg of norethindrone acetate. In

addition to preventing undesired pregnancies, these formulations are associated with a

high degree of menstrual regularity and can be used to treat symptoms associated with a

high degree of menstrual regularity and can be used to treat symptoms associated with

relative estrogen deficiency. The use of oral contraceptive until menopause has been 11

found to be safe in women with no risk factors for cardiovascular disease. Before

starting the administration of oral contraceptives in this age group, patients should be free

of the following risk factors : hypertension, hypercholesterolemia, cigarette smoking,

previous thromboembolic disorders, cerebral vascular disease, or coronary artery disease.

The levonorgestrel – releasing intrauterine device (IUD) is able to release 20 mcg of

levonorgestrel per day to act locally at the level of the uterus. This system has been

shown to be effective for endometrial protection during estrogen therapy. In patients with

dysfunctional uterine bleeding, this progesterone IUD was found to be equally effective

compared with endometrial resection after a 1 – year follow – up. In a population of

women with menorrhagia, levonogestrel – releasing IUDs compared similarly to 12

hysterectomy but at a significantly lower cost.

SURGICAL METHODS :

Hysrerectomy is the second most common operative procedure after caesarean section

among reproductive aged women. The average age at hysterectomy is 44.5 with same

regional variation. Although it is a very effective surgical procedure, hysterectomy is

associated with a certain degree of morbidity and cost. Prior to recommending a

hysterectomy, an adequate preoperative evaluation must include endometrial sampling

and an adequate trial of hormonal therapy to control the bleeding.

The Maine Women's Health Study analysed close to 600 women with these complaints

and found that patients with abnormal uterine bleeding who were treated initially with

nonsurgical management (cyclic progestins, oral contraceptives, or nonsteroidal anti-

inflammatory medicines) had a statistically significant improvement in symptoms through

one year of follow-up. However, close to 25 % went onto have a hysterectomy after the

year of nonsurgical management and noted highly effective relief and improvement in 13

quality of life as measured by surveys.

ENDOMETRIAL ABLATION :

Surgical alternatives to hysterectomy offer less radical and potentially more cost effective

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methods to treat menorrhagia. Endometrial ablation using lasers or electro cautery or

thermal balloon ablation has been used and demonstrates an amenorrhoea rate of upto 50

% and patients satisfaction close to 90 %.

A large prospective cohort study noted that 80 % of endometrial ablation patients needed

no further surgery, whereas 9% underwent hysterectomy within 5 years of the initial

procedure.14 However, endometrial ablation offers immediate results and has been shown

to be effective on its own, without the need for pretreatment in a benign setting.

SUMMARY:

The management of benign symptoms, diagnosing and treating serious pathology is a

complex balance when viewed in the light of the vast treatment options available. A

detailed history and appropriate testing remain the principal starting point to providing

better care for a woman during her reproductive aging process.

PERIMENOPAUSAL BLEEDING WORKUP AN ALGORITHM

Abnormal Bleeding

Anovulatory bleeding, Ut. Fibroids, polyps, endometrial hyperplasia, endometrial carcinoma.

Menstrual History Laboratory Work UpHb %, PCB, Complete Haemogram, FSH-E , 2

T , T4 TSH3 ,

Trans Vaginal UltrasoundI Hysterosonography

Endometrial Biopsy (Pipelle)

Simple Hyperplasia or normal Pathology

Tissue Insufficient

Hysteroscopy

Normal

Abnormal

Complex Hyperplasia orMalignancy

Hysteroscopy & Curettage

Non Hormonal / Hormonal Treatment

Repeat Endometrial BiopsyIn 6 months for

Hyperplasia

Simple Hyperplasia

Atypical Hyperplasia orMalignancy

Hysterectomy

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Bibliography :

1. Akas Jain and Nanette Santoro – Endocrine Mechanisms and Management for

Abnormal Bleeding due to Perimenopausal Changes – Clinical Ostetrics & Gynaecology

– 2005 ; Vol. 1, No. 4, 419 – 435.

2. Brambilla DJ, McKinlay SM, Johannes CB, Defining the perimenopause for application

in epidemiologic investigations. Am J Epidemiol. 1994 ; 140 : 1091 – 1095.

3. William W. Hurd – Menopause – Novaks Gynaecology Text Book – 12th Edition ; Chapter

29 : 981 – 1011.

4. Fraser IS, McCarron G, Markham R. A Preliminary study of factors influencing

perception of menstrual blood loss volume. Am J Obstet Gynaecol. 1984 ; 149 : 788 – 793.

5. Santoro N, Brown JR, Adel T, et al. Characterization of reproductive hormonal

dynamics in the perimenopause, J Clin Endocrinol Metab. 1996 ; 81 : 1495 – 1501.

6. Belsey Em, Pinol AP. Menstrual bleeding patterns in untreated women. Task Force on

Long – Acting Systemic Agents for Fertility Regulation. Contraception. 1997 ; 55 : 57 – 65.

7. Stovall TG, Photopulos GJ, Poston WM, et al. Pipelle endometrial sampling in patients

with known endometrial carcinoma. Obstet Gynaecol. 1991 ; 77 : 954 – 956.

8. Goldstein SR. Use of ultrasonohysterography for triage of perimenopausal patients

with unexplained uterine bleeding. AM J Obstet Gynaecol. 1994 ; 170 : 565 – 570.

9. Jennings JC. Abnormal uterine bleeding Med Clin North Am. 1995 ; 79 : 1357 – 1376.

10. Bishop PM, Cabral de Almeida JC. Treatment of functional menstrual disorders with

norethisterone. Br Med J. 1960 ; 5179 : 1103 – 1105.

11. Marshall LM,. Spiegelman D, Barbieri RL, et al. Variation in the incidence of uterine

leiomyoma among premenopausal women by age and race. Obstet Gynaecol. 1997 ; 90 :

967 – 973,

12. Hurskainen R, Teperi J, Rissanen P, et al. Quality of life and cost-effectiveness of

levonogestrel-releasing intrauterine system versus hysterectomy for treatment of

menorrhagia : a randomized trial. Lancet. 2001 ; 357 : 273 – 277.

13. Carlson KJ, Miller BA, Fowler FJ Jr. The Maine Women's Health Study : I. Outcomes of

hysterectomy. Obstet Gynaecol. 1994 ; 83 : 556 – 565.

14. O'Connor H, Magos A. Endometrial resection for the treatment of menorrhagia. N

Engl J Med. 1996 ; 335 : 151 – 156.

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HEREDITARY ANEMIAS

Dr. Hema DivakarDivakars speciality hospital Bangalore India

Anemia is the commonest medical disorder in pregnancy having varied incidence, etiology and

degree of severity in different populations with the prevalence ranging between 35 to 75 % in

developing countries. (ref 1, 2).

Anemias can be classified according to clinical, morphologic or etiologic factors and

characteristics. There are advantages to each system and they mesh with each other.

Clinical classification allows the physician to adjust the pace of diagnosis and treatment

according to the severity of the patient's condition.

Morphologic classification, based on examination of peripheral smear, is the most common way

to arrive at a specific diagnosis and a good way to proceed in a cost effective search for the source

of anemia.

Etiologic classification describes hereditary anemias and acquired anemias.

This article will detail the HEREDITARY ANEMIAS. These are due to intrinsic defects in the

erythrocyte membrane, glycolytic pathway, glutathione metabolism or haemoglobin molecule.

Since iron deficiency anemia is the most common, many clinicians would initiate therapy and re-

evaluate in one month.

If anemia fails to improve, a more intensive clinical and laboratory evaluation is justified.

Thalassemia is hereditary condition which can be aggravated by pregnancy.

It results when an insufficient amount of hemoglobin is produced to fill the red blood cells.

The unbalanced synthesis of hemoglobin leads to premature RBC death and results in severe

anemia.

This is being detailed in a separate article.

Sickle cell anemia is a hereditary birth defect. It is a recessive, hereditary, familial hemolytic

anemia where abnormal hemoglobin types (SS or SC) produce recurrent attacks (crisis) of pain

and fever.

In sickle cell disease though, this hemoglobin becomes moon (or sickle) shaped, and cannot fit

through the blood vessels properly.

As a result, people with sickle-cell anemia don't get enough oxygen delivered throughout their

bodies causing extreme fatigue.

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These sickle-shaped cells can also clog the blood vessels, causing tissue damage, organ failure,

and even death.

Sickle cell anemia is most common among African Americans, with about 2 million African

Americans carrying the sickle cell trait.

People who carry the sickle cell gene but do not have sickle cell anemia are said to have "sickle cell

trait".

If both partners carry sickle cell gene - it is passed on to the child. If only one partner carries the

gene , the offspring will be a carrier. Amniocentesis can be performed between the 14th and 16th

week of pregnancy to determine if the fetus has sickle cell anemia.

Sickle cell symptoms tend to vary from person to person. They also tend to increase in severity as

you age.

Common sickle cell symptoms include:

v pain in the stomach, legs, and arms

v chest pain

v jaundice

v extreme fatigue

v growth problems

v frequent illness and infection

Possible complications include:

v Vision Loss: Sickle-shaped hemoglobin cells can block the tiny blood vessels

surrounding the eyes, causing vision loss.

v Organ Damage: Blocked blood vessels can cut off blood and oxygen supply to key

organs, including the liver, kidney, and spleen.

v Stroke: Blocked blood vessels can prevent oxygen supply to the brain, causing a stroke.

v Acute Chest Syndrome: People with sickle cell anemia are highly susceptible to

infection.

v Acute chest syndrome is similar to pneumonia and can cause fever, pain, and breathing

problems.

Laboratory Studies show reticulocytosis except during aplastic crisis. The peripheral smear

shows sickle cells, holly leaf cells or Howell Jolly bodies. The Hb electrophoresis shows varying

amounts of Hb S and Hb F .

Treatment:

There is no treatment for sickle cell anemia.

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Common management includes:

v penicillin injections to prevent and fight infections

v pain medications

v folic acid supplements, to help grow new red blood cells

v blood transfusions, to increase the number of healthy red blood cells

v bone marrow transplants to help the body create healthy red blood cells

Transfusions are required to keep the hematocrit level at least 30%. Nagel and co workers (3)

reported that recombinant human erythropoietin can stimulate the F reticulocyte responses

In a randomized trial , Charache and colleges reported that hydroxyurea therapy ameliorated the

clinical course of the disease.(4)

Perrine and collegues reported the response of the patients to infusions of arginine butyrate (5)

A remarkable trial (6) of zinc supplementation in the prevention of vaso-occlusive episodes and a

significant reduction in the infective episodes is encouraging.

Pregnancy outcomes in sickling syndromes are highly variable and needs extensive expertise for

procedures like partial exchange transfusions.

Hb C disease – has Hb C

In the heterozygous state, illness is rare unless associated with sickling.

In the homozygous state, relatively insoluble Hb C crystallsises in the oxy haemoglobin state,

causing the red cells to become rigid.

Fragmentation and loss of membrane material leads to the presence of microspherocytes on the

peripheral smear.

Prenatal diagnosis is needed only if SC disease (sickle and Hb C) is suspected.

Symptoms are rare and maternal and perinatal outcomes are good.

Hb E disease – has Hb E

A specific gene defect in the DNA for Hb E results in abnormal splicing leading to defective chain

synthesis. Hence it resembles thalasemmia intermedia. Hb E trait affects 25 % of Southeast Asian

women (7) and has been reported in 50 % of an isolated population in India.(8) Growth restriction

and fetal wastage can occur in those with homozygous Hb E (9) (10).

Hereditary spherocytosis

Hereditary spherocytosis is the commonest form of haemolytic anaemia seen in northern Europe

and it is important to know that most children who have mild disease, can live a normal life, and

do not require splenectomy.

It is one specific familial hemolytic disorder characterized by marked heterogeneity of clinical

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features, ranging from an asymptomatic condition to fulminant and extremely serious hemolytic

anemia.

The most common characteristic of hereditary spherocytosis is one structure called the

microspherocyte- the sphere-shaped red blood cell, which is caused by loss of membrane surface

area, and an abnormal osmotic fragility in vitro.

Because the spherocytes have a smaller surface area through which oxygen and carbon dioxide

can be exchanged- they perform adequately to maintain healthy oxygen supplies. However, they

have a high osmotic fragility -when placed into water, they are likely to burst.

Frequency of the condition:

Hereditary spherocytosis is the most common of the hereditary hemolytic anemias among people.

Researches done in the past have proven that, in the United States, the incidence of the disorder is

approximately 1 case in 5000 people.

It is proven that this condition is usually transmitted as an autosomal dominant trait, and the

identification of the disorder in multiple generations of affected families is the rule. An autosomal

recessive. The The disease is also encountered worldwide, but its incidence and prevalence in

other groups are not established clearly.

Anemia or hyperbilirubinemia may be of such magnitude as to require exchange transfusion in

the neonatal period.

Anemia usually is mild to moderate; however, sometimes it is very severe and sometimes it is not

present.

Splenomegaly is the rule, and palpable spleens have been detected in more than 75% of affected

subjects.

Severe hemolytic anemia requires red cell transfusions.

Mechanism of the condition:

The most important thing there is to know about this condition is that the defects in hereditary

spherocytosis are in the red cell membrane.

This is because the proteins essential for the integrityof the membrane structure lie immediately

under the lipid layer.

It is proven that different genes code each of these proteins, thus hereditary spherocytosisis a

heterogeneous disorder..

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Symptoms of the condition:

Every patient should know that the spleen's hemolysis results directly in varying degrees of

anemia and hyperbilirubinemia.

These two conditions can result in symptoms of:

v Fatigue

v Pallor

v Jaundice

Chronic symptoms include anemia and splenomegaly.

Lab Studies:

The classic laboratory features of this type of anemia include minimal or no anemia,

reticulocytosis, an increased mean corpuscular hemoglobin concentration (MCHC), spherocytes

on the peripheral blood smear, hyperbilirubinemia, and abnormal results on the osmotic fragility

test. Other biochemical changes of hemolysis also are also present, including:

v increased lactate dehydrogenase (LDH)

v increased unconjugated bilirubin

v decreased serum haptoglobin

v an increase in MCHC

The treatment of this type of anemia involves pre-splenectomy care, splenectomy, and post-

splenectomy complications. Problem is that children

with severe hyperbilirubinemia caused by this type of anemia are at risk for kernicterus, and

these infants should be treated with phototherapy and exchange transfusion as clinically

indicated.

Iron supplementation:

Researches are showing that iron supplementation supports the increased production of red

blood cells, but in longstanding cases in which patients have taken supplemental iron or received

numerous blood transfusions; iron overload may be a significant problem, being a potential cause

of cardiomyopathy and liver disease.

The hereditary stomatocytosis syndromes

The hereditary stomatocytosis syndromes and allied disorders are usually transmitted in an

autosomal dominant pattern, although apparently sporadic cases have been reported.

Penetrance is variable, with significant disparity in clinical symptomatology between affected

individuals in the same kindred.

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Many patients present with hemolytic anemia in the neonatal period, but others are

asymptomatic throughout their lifetime.

Aplastic crises associated with parvovirus and other infections have been reported.

An unusual characteristic of the stomatocytosis syndromes is a predisposition to severe life-

threatening thrombosis after splenectomy.

Enzyme deficiency anemias

G6PD deficiency – X linked recessive trait high prevalence

G6PD is the key enzyme in the hexose mono phosphate shunt.

Lack of G6PD lessens the reducing power of the erythrocyte.producing rigid membranes and

Henz bodies.

Diagnosis is by exclusion

Treatment includes Vit E and Folic acid supplementation.

Prognosis is good.

PK pyruvate kinase defeciancy and G6PI glucose 6 phosphate isomerase deficiencies show

symptoms of anemia, jaundice and splenomegaly.

Fetal hydrops and spontaneous abortions are associated with enzyme deficiency anemia.

Conclusions :

Though iron deficiency anemia is a common problem, there are other non-nutritional anemias

that may be seen.

Some of these may manifest for the first time in pregnancy.

Although these conditions are rare, it is important for the obstetrician to recognize these and

initiate appropriate interventions, if and when required.

References

v Die jamaron FME, Abdulaziz A – Anemia in pregnancy – Int J Glyrol obst -1999

v Shehwartz WJ; Tumanu- Iron Deficiency anemia in pregnancy – Clin .obst Gynecol -1993

v Nagel RL ,Shah M, et al. F reticulocyte response in sickle cell anemia treated with

recombinant human erythropoietin: a double-blind study.Blood-1993

v Charache S, Terrin ML,Moore RD,et al. Effect of hydroxyurea on the frequency of

painful crises in sickle cell anemia. New England J of Medicine-1995

v Perrine SP,Ginder GD,Faller DV,et al.A short –term trial of butyrate to stimulate fetal-

globin-gene expression in the beta-globin disorder. N Eng J Med-1993

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v Gupa VA,Chaubey SB.Efficacy of Zinc therapy in prevention of crisis in sickle cell

anemia:a double bind ,randomized controlled clinical trial.J Assc Physicians India-1995

v Pravatmuang P,Tilokhus M, Suannum M,Chaipat C.Phitsanulok population:the highest

incidence of hemoglobin E in the northen provinces of Thiland and PND

Counseling.Southeast Asian J Trop Med Public Health-1995

v Deka R,Fertility and hemoglobin genotypes:a population study in upper Assam.Hum

Genet-1981

v Ong HC.Maternal and fetal outcome associated with hemoglobin E trait and hemoglobin

E disease. Obstet Gynecol-1975

v Belgir RS. Reproductive profile of mothersin relation to hemoglobin E genotypes.Indian

J Pediatr_1992

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ACQUIRED HEMOLYTIC ANEMIAS

Biliangady Harsha N. MDAssociate Professor

Kempegowda Institute of Medical SciencesSonologist 'NORTH STAR' Women's Hospital,

Bangalore

Definition: Hemolytic anemias develop from an increase in the rate of red cell destruction.

The normal life span of red cells is 100 - 120 days; in hemolytic anemias this is shortened by

varying degrees and may be a few days only in severe cases.

Classification: There are two basic causes of red cell destruction

1. Intracorpuscular (Intrinsic) i.e. abnormality of the red cells which results in premature

destruction i.e. if these patients are transfused with normal red cells, the transfused cells,

have a normal life span. The condition is mainly congenital due to an abnormality in the

red cell itself i.e. in the membrane itself.

2. An Extracorpuscular (Extrinsic) i.e. development of an abnormal hemolytic mechanism.

Normal compatible red cells are prematurely hemolysed. Whereas red cells from these

patients when transfused to a normal individual will have a normal life span. In other

words these individuals have normal red cells but have developed an abnormal

hemolytic mechanism i.e. there is an acquired hemolytic process or more accurately an

auto immune acquired hemolytic anemia.

AUTO IMMUNE ACQUIRED HEMOLYTIC ANEMIA (AIHA)

AIHA is a group of disorders due to formation of antibodies against the antigens on the surface of

the patients own red cells, i.e. they act as auto – antibodies. The antibodies are most often IgG or

less often IgM or IgA. Some are known to bind complement also. These auto - antibodies may

form as a result of breakdown of T – cell regulation of B cells with the emergence of a hostile clone

of immunocytes. Or, a change in the structure of the surface antigen on red cell is recognized as

'non self' by the immune system. In reality the pathogenesis of AIHA is not really known. AIHA

is not a rare disorder and occurs in all grades of severity ranging from a chronic mild

asymptomatic condition to a rapidly acutely fatal state.

CLASSIFICATION OF AIHA: AIHA is classified depending upon the

1. The temperature at which the antibody reacts with the red cells into warm and cold

antibody types (table1).

2. According etiology in to idiopathic and secondary types (table2).

Warm AIHA: Seen more frequently in adults than in children and the idiopathic form is seen

more often in women over the age of forty. The most important causes of secondary AIHA are

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chronic lymphocytic leukemia; malignant lymphoma and systemic lupus erythematosus (SLE).

Some drugs like methyldopa are known to cause secondary AIHA. Its use as an antihypertensive

is now rare but is still popular in the management of pregnancy induced hypertension (PIH).

Clinical Features: An insidious onset with features of anemia is usual. In secondary AIHA the

underlying disease is ongoing at the time of hemolysis. Mild to moderate jaundice is present but is

persistently absent in about 25% of the patients. The spleen is always enlarged and is nearly

always palpable, but rarely beyond the limits of the umbilicus. A very large spleen suggests a

chronic lymphocytic leukemia or malignant lymphoma. Moderate hepatomegaly is present but

lymphnode enlargement does not occur in idiopathic cases though it is a common finding in

secondary AIHA. Hemoglobinuria is occasionally seen. In young children and some adults the

onset is sudden following a minor viral or bacterial infection. Intravascular hemolysis is seen as a

hemoglobinemia and hemoglobinuria; oliguria and anuria are rare. Hemolysis normally stops on

its own and is followed by complete recovery. Death occurs rarely when the condition is severe.

Blood Picture: The typical feature is one of reticulocytosis with spherocytosis and positive direct

antiglobuilin test. Reticulocyte count ranges from 5 – 30 % but can be higher. Rarely reticulocye 1

count may be normal or even reduced in an aplastic crisis . Spherocytosis is present in active

disease as is evidenced by a raised osmotic fragility and if mild this may be the only clue as it is 1

unlikely to appear on a blood film. A mild increase in MCV is common .

Polychromatic macrocytes are prominent in a blood film with a high reticulocyte count.

Leucocytosis is seen in acute severe case, and counts of 20 – 30 x 109/L or more are quite common

in chronic moderate cases the count is often normal or very rarely moderately reduced. Platelet

counts are mostly normal or sometimes low enough to cause purpura. Serum bilirubin is between

17 – 50µmol/L. Erythrocyte sedimentation rate (ESR) is markedly elevated in the active phase

returning to normal during remission. Immunoglobulins are reduced in about 50% of the women

the deficiency being IgA most commonly, but IgG and/or IgM deficiency or deficiency of all three

are also seen. Blood drawn for routine examination shows mild agglutination in the collection o

tube and blood film. This is not prevented by drawing blood into pre warmed syringes at 37 C,

representing red cells coated heavily with incomplete antibody. This should not be mistaken for

the more intense agglutination of Cold Hemagglutinin Disease.

Antibodies on the red cell surface: This is detected by positive direct antiglobulin testing using a

broad - spectrum reagent. Monospecific reagents are more precise and it is found that 56% show a

coating with IgG and complement C3, 35% have IgG alone and IgA and IgM. In SLE the red cell

coating is almost always IgG and complement. With methyldopa induced hemolysis it is IgG 2

alone . It is important to understand that there are numerous causes for a positive direct

antiglobulin test besides AIHA. Methyldopa is an important cause for positive antiglobulin test

even in the absence of active hemolysis.

Diagnosis: Typical findings of hemolytic anemia including jaundice, splenomegaly,

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reticulocytosis and an increased serum bilirubin with a positive direct antiglobulin test. 25% may

not have jaundice. Bone marrow aspiration or a trephine biopsy is indicated and a careful search

for evidence of leukemia, malignant lymphoma and megaloblastic red cells is made. Tests for SLE

must be conducted, in acute cases. In children viral infections must be ruled out.

Course and Prognosis: The course of the idiopathic form of the disease is variable and forecasting

the outcome is difficult. Most patients respond initially to some form of treatment. In chronic

disease hemolysis may continue for years, the disability depending upon the degree of anemia.

No patient is cured if the antiglobulin test remains positive even if hemoglobin, reticulocyte count

and serum bilirubin have returned to normal. A Mayo Clinic study on survival rates has found 3

91% and 73% at one year and ten years respectively .

Treatment: In most adults and children with severe disease corticosteroids, blood transfusion

and splenectomy form the key to management. Immunosuppression may be necessary for some.

Corticosteroids: Induce prompt remission in about 80% of cases. The dose of prednisone varies

from 60 – 80 mg/day to start with, and 5 – 15 mg/day maintenance to keep the hemoglobin at

11Gm%. Patients requiring more than 15mg of prednisone will be benefited by splenectomy.

Corticosteroid therapy is deemed to have failed if there is no improvement after three weeks of

treatment.

Blood Transfusion: Is not necessary in moderate cases. In severe cases packed red cells are used

to maintain hemoglobin levels and blood volume. The auto - antibodies on the red cell surface

interfere with grouping and cross matching and this must be performed by an experienced 4

transfusion specialist. Guidelines for transfusion in AIHA must be strictly followed .

Splenectomy: Is reserved for

1. Idiopathic cases not responding to adequate treatment with steroids and secondary

AIHA not responding to treatment of the underlying cause.

2. Patients requiring large doses of steroids to maintain adequate hemoglobin levels.

Sometimes complete remission may not be achieved but at least the dose of steroid

required is reduced. It is important to explore the abdomen for accessory spleens and

ovarian dermoids. A histopathological examination of the spleen may be the first clue to

a malignant lymphoma.

Immunosuppressive Therapy: Generally reserved for patients that do not respond to

splenectomy and are requiring high doses of steroids. The drugs used are Azathioprine 2.0 – 2.25

mg daily or Cyclophosphamide 1.5 – 2.0 mg daily. Neutrophil count must be carefully monitored

and long term Azathioprine therapy is sometimes associated with the development of malignant 5

lymphoma . All patients with continuing hemolysis must get 5.0 mg of Folic acid/day.

Treatment for secondary AIHA is as in idiopathic AIHA with concurrent management of the

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causative disorder. When AIHA develops in a patient with a previous H/O malignant

lymphoma or other neoplasm a thorough check for recurrence must be made.

COLD ANTIBODY AUTO IMMUNE ACQUIRED HEMOLYTIC ANEMIA

oAIHA due to cold antibodies that react with red cells at temperatures less than 37 C, are less

common than the warm antibody type.

Two forms are recognized

1. Cold Hemagglutinin Disease (CHAD) characterized by antibodies that react with red

cells at low temperatures.

2. Paroxysmal Cold Hemoglobinuria (PCH) characterized by episodes of acute hemolysis

due to auto - antibodies that act primarily on red cell lysins at low temperatures.

Both CHAD and PCH can be idiopathic or secondary to an underlying disease.

Cold Hemagglutinin Disease: Idiopathic CHAD is seen in adults over 50 years of age. It is rare in

children with most patients running a chronic course. Unlike warm AIHA, CHAD is equally

distributed between men and women. The secondary form occurs as a rare complication of SLE,

malignant lymphoma and chronic lymphocytic leukemia, or a transient anemia secondary to 6

infectious mononucleosis (Table 2).

Clinical Features: In idiopathic CHAD and in CHAD associated with SLE, malignant lymphoma

or chronic leucocytic leukemia the onset is insidious. Two patterns are seen depending on the

thermal range of the antibodies.

Some experience acute intravascular hemolysis and hemoglobinuria in winter and have normal

hemoglobin in summer. Others are well compensated with mild or moderate chronic hemolytic

anemia which worsens only slightly in winter. Agglutination occurs in the peripheral cooler parts

of the circulation causing varying extents of microvascular obstruction and signs of cold

sensitivity ranging from Raynaud's phenomenon, acrocynosis and rarely peripheral gangrene.

These phenomena are seen most often in winter and are unlikely to be seen in temperate climates.

Very rarely a terminal complication of CHAD can be a malignant lymphoma, but more frequently 7

CHAD develops in patients with pre existing lymphoma .

Post infectious CHAD has an acute onset during the second or third week of infection. Acute

intravascular hemolysis, jaundice and splenomegaly are seen. Cold sensitivity is usually not seen

and hemolysis takes up to 2 – 3 weeks to resolve.

Blood Picture: Picture of anemia with red cell agglutination, reticulocytosis and a positive direct

antiglobulin test. Red cell agglutination is an outstanding feature. This picture is seen on films

prepared from capillary blood or blood collected into an anticoagulant and is often seen

macroscopically in the collection tube. Agglutination can be prevented by using pre warmed

syringes and slides kept at 37oC. Hemoglobin is rarely below 8g/dl. Spherocytosis is less marked

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than in warm AIHA. Reticulocyte count is only mildly increased. Polychromatic macrocytes and

occasional nucleated red cells are seen. White cell count and platelets are normal. Serum bilirubin

is only mildly raised and plasma hemoglobin appears only during active disease, but

hemosiderin is seen in the urine during both active and quiescent phases. Red cell agglutinates

interfere with the functioning of automated counters giving falsely high MCV. Serum and red cell

folate might be reduced.

Immunology: Most cases of CHAD are caused by an auto - antibody referred to as anti – I. This

anti body reacts with the I antigen found on the red cell surface of all adults but not fetal RBC. This o

is a complete antibody which is inactivated at 37 C but agglutinates red cells with increasing o

strength as the temperature drops towards 4 C. The lytic activity of this antibody is much less

compared to that of the Donath – Landsteiner anti body of paroxysmal hemoglobinuria.

The anti – I antibodies of both idiopathic and secondary CHAD are IgM type with ê light chains.

Serum IgM levels are elevated above 6 g/L and IgG and IgA are normal. The anti – I antibody of

CHAD secondary to mycoplasma infection is also an IgM, but is polyclonal consisting of ê and ë

light chains.

oThe direct anti globulin test is positive if blood is drawn and kept at 37 C and washed in warm

saline before testing. The positive test is due to the presence of complement C3d on the red cell

surface.

Prognosis and Treatment: The idiopathic disease progresses slowly and many patients remain o

relatively well especially when upper thermal ranges of the antibody does not exceed 28 C.

Protection from cold or a shift to temperate climate is often enough. Corticosteroids and

splenectomy are rarely effective. Chlorambucil is useful and reduction of IgM in the serum is seen.

When transfusion is necessary pre warmed concentrated red cells are transfused keeping the

patient warm.

Paroxysmal Cold Hemoglobinuria (PCH): A rare disorder seen as attacks of hemolysis with

hemoglobinuria on exposure to cold. The condition develops due to the development of a cold

auto - antibody with strong lytic activity. The blood shows a characteristic bithermic cold

hemolysin that is demonstrated by the Donath – Landsteiner test.

The principle of the test is that the hemolysin in the patient's blood attaches to sensitized red cells o

when chilled and then hemolysed by complement when warmed to 37 C. This cold hemolysin is a

complement binding IgG antibody having anti – p blood group specificity.

Paroxysmal Nocturnal Hemoglobinuria: This rare disorder is associated with a chronic

hemolytic anemia and intermittent hemoglobinuria. The abnormality is an acquired defect of the

red cell membrane making the cells unusually sensitive to lysis by the complement of normal 8

serum. Three cell lines of red cells have been detected in PNH ; two populations of

intermediate and extreme sensitivity to complement lysis and a third resistant population.

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Appears usually between 30 – 40 years and affects men and women equally. Hemoglobinuria is

seen in all patients and is related to sleep irrespective of sleeping time. Characteristically night

urine or the first morning sample is colored. Hemosiderinuria is always present and at autopsy

renal tubules are laden with hemosiderin. Red cells are not found in the urine.

Blood picture: Shows anemia of varying intensity. Moderate macrocytosis, polychromasia and

moderate leucopenia are observed. Reticulocytes are increased but not to the expected extent for

the anemia present.

Diagnosis: This is made by the intermittent hemoglobinuria and presence of hemosiderin in

urine. The condition should be suspected in patients with refractory anemia. Showing a

pancytopenia, reticulocytosis or if a H/O transfusion reaction is present.

Treatment: No specific treatment is available; management is mostly supportive with 9

concentrated red cells as transfused red cells have a normal life span. Oxymethalone 10 -50 mg

and androgens can be used. Splenectomy is of no value.

Hemolytic Anemia Due To Drugs and Chemicals: Many drugs cause hemolysis and they fall

into three categories.

1. Those that have a direct toxic action on the red cells, hemolysis is dose related and occurs

in most normal subjects provided that sufficient dose of the drug is administered.

2. Those that cause hemolysis as a result of a hereditary metabolic abnormality of the red

cells.

3. Those that cause hemolysis by an immunological mechanism (Table 3).

TABLE 1. WARM AND COLD ANTIBODIES IN AIHA

WARM COLD AIHA

*CHAD

†PCH

Immunoglobulin Class IgG IgM IgG

Optimal reaction temperature

o37 C

o0 - 4 C

o0 - 4 C

Antibody specificity Often anti Rh Anti - PAnti -I or anti - I

Immunochemical characteristics

Polyclonal Monoclonal Polyclonal

Serological behavior in vitro

Incomplete Agglutinin Bipahsic hemolysin

Protein on red cell IgG 35%IgG +C56%C 9%

C 100% C 100%

Legend: * Cold Hemagglutitnin Disease † Paroxysmal Cold Hemoglobin Uria

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TABLE : 2 CLASSIFICATION OF AUTO - IMMUNE ACQUIRED HEMOLYTIC ANEMIA

Idiopathic 50%

Secondary 50%

Drugs: Methyldopa, mefenemic acid, L-dopa , procaine amide

Infections: Mycoplasma pneumoniae, infectious mononucleosis, cytomegalovirus.

Chronic lymphocytic leukemia

Malignant lymphomas

Systemic lupus erythematosus

Other autoimmune diseases rheumatoid arthritis, chronic active hepatitis, myasthenia gravis, ulcerative colitis

Miscellaneous - carcinoma, sarcoidosis, ovarian teratoma

TABLE : 3DRUGS AND CHEMICAL AGENTS THAT MAY CAUSE HEMOLYTIC ANEMIA

Drugs that regularly cause hemolytic anemia in normal subjects by direct toxic action

Acetylphenylhydrazine Phenylhydrazine

Arsine Potassium chlorate

Chloramine Resorcinol

Copper Sodium chlorate

Formaldehyde Sulphanilamide

Naphthalene Sulphapyridine

Para aminosalicylic acid Sulphasalazine

Phenacetine Sulphones

Phenazopyridine

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* In addition to these drugs, many of the agents causing hemolysis in large doses will cause hemolysis in small doses in G6PD defiant patients.

TABLE 3DRUGS AND CHEMICAL AGENTS THAT MAY CAUSE HEMOLYTIC ANEMIA

Drugs that cause hemolytic anemia in subjects with hereditary *

metabolic abnormalities of the red cell ((principally G6PD deficiency)

Analgesics Sulphones

Acetanilide Dapsone, Thiazole sulphone

AntimalarialsPamaquinPentaquinPrimaquin

MiscellaneousAcetyphenylhydrazineMethylene blueNalidixic acidNaphthalelneNiridazolePhenylhydrazine Trinitrotoluene

NitrofuransNitrofurantoin

SulphonamidesSulphacetamideSulmethoxazoleSulphanilamideSulphapyridineSulphasalazine

ImmuneAmidopyridineAntazolineCephalosporinesChlorpropamideCisplatin

SulphasalazineStibophenSulphonamidesTeniposideTetracyclineThiazides

Drugs that cause hemolytic anemia by immune mechanism

DipyroneErthromycinInsulinIsoniazidNomifesinePara aminosalicylic acidParacetamol

* *Thiopentone 13TolbutamideTriamterene

Auto - immuneL - dopaMefenemic acidProcaineamide

PenicillinPhenacitinQuinidineQuinineRifampicin

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References

1. Liestveld J.L. et al Variability of erythropoietic response in auto immune hemolytic anemia,

Immune Hemolytic Anemia Methods in Hematology; Chaplin H (Ed): 987.

2. Isis .P. Serological diagnosis and characterization of causative antibodies ; Immune

Hemolytic Anemia, Methods in Hematology; Chaplin H (Ed): 1985.

3. Silverstein .M.N et al Idiopathic Acquired Hemolytic Anemia, Survival in 117 cases; Arch Int

Med: 129 (1972).

4. Masouredis . S. P. et al Transfusion Management of auto immune hemolytic anemia,

Immune Hemolytic Anemias Methods in Hematology Volume 12; 1985.

5. Grunwald H.W. et al Acute leukemia and Immunosuppressive drug use, Arch Int Med , 139;

461: 1979.

6. Crisp D & Pruzanski W. B – cell neoplasms with homogeneous cold reacting antibodies (cold

agglutinins); Am J Med 72; 915: 1982.

7. Chaplin H. Lymphoma in primary cold hemagglutinin disease treated with chlorambucil,

Arch Int Med ; 142: 2119 1982.

8. Rosse W.F et al The population of red cells in paroxysmal nocturnal hemoglobinuria of

intermediate sensitivity to complement lysis significance and mechanism of increased

immune lysis Brit J Hemat: 28:181 1974

9. Rosse W.F Treatment of paroxysmal Nocturnal Hemoglobinuria, Blood; 60: 20, 1982.

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THALASSEMIA AND PREGNANCY

Dr. Narayanan. R. Malathi Memorial Hospital Bangalore

The name thalassemia was coined at the University of Rochester in New York by the Nobel Prize-

winning pathologist George Whipple and the professor of pediatrics William Bradford from the

Greek thalassa for sea and -emia, meaning the blood. Thalassemia means "sea in the blood." But

for the Greeks, the sea was the Mediterranean, so thalassemia also conveys the idea of the

Mediterrranean in the blood.

The reason that the gene for beta thalassemia is relatively common, among people of Italian and

Greek origin is that parts of Italy and Greece were once full of malaria. The presence of

thalassemia minor (like sickle cell trait in Africa) afforded protection against malaria, and

therefore, this gene thrived. In India too, thalassemia is common in areas like the Kutch where

malaria was once endemic.

Thalassemia is the most common autosomal recessive genetic blood disorder that affects the

production of hemoglobin, resulting in anemia. It is estimated that there are 200,000 thalassemics

in the world among whom 5000 to 8000 are in India. About 100,000 babies worldwide are born

with severe forms of thalassemia each year. Thalassemia occurs most frequently in people of

Italian, Greek, Middle Eastern, Southern Asian and African ancestry.

The two main types of thalassemia are called "alpha" and "beta," depending on which part of an

oxygen-carrying protein in the red blood cells is lacking. Both types of thalassemia are inherited

in the same manner. The disease is passed to children by parents who carry the mutated

thalassemia gene. A child who inherits one mutated gene is a carrier, which is sometimes called

"thalassemia trait." Most carriers lead completely normal, healthy lives.

A child who inherits two thalassemia trait genes - one from each parent - will have the disease. A

child of two carriers has a 25 percent chance of receiving two trait genes and developing the

disease, and a 50 percent chance of being a thalassemia carrier. If one of the partners is a carrier the

offspring has no risk of being a thalassemic, but 50% chance of being a carrier (Diagrams).

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Alpha Thalassemia:

Most individuals with alpha thalassemia have milder forms of the disease, with varying degrees

of anemia. The most severe form of alpha thalassemia, which affects mainly individuals of

Southeast Asian, Chinese and Filipino ancestry, results in fetal or newborn death.

Diagram depicting the transmission of Thalassemic gene to the offspring when both partners are carriers:

T

TN

N N

N

N

T

T

TNTN

25% Thalassemic 50% Carrier 25% Normal

NormalCarrier

Thalassemia

T

---

T N N

TN

50% Carrier

N

TN NN NN

50% Normal

TNNT

NormalCarrier

Thalassemia---

Diagram depicting transmission of Thalassemic gene if one partner is a carrier:

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Beta Thalassemia:

The most familiar type of thalassemia is beta thalassemia. It involves decreased production of

normal adult hemoglobin (Hb A), the predominant type of hemoglobin which begins soon after

birth and continues until death. The globin part of Hb A has 4 protein sections called polypeptide

chains. Two of these chains are identical and are designated the alpha chains. The other two

chains are also identical to one another but differ from the alpha chains and are termed the beta

chains. In persons with beta thalassemia, there is reduced or absent production of beta globin

chains.

There are two forms of beta thalassemia. They are thalassemia minor and thalassemia major

(which is also called Cooley's anemia).

Thalassemia minor: The individual with thalassemia minor has only one copy of the beta

thalassemia gene (together with one perfectly normal beta-chain gene). The person is said to be

heterozygous for beta thalassemia.

Persons with thalassemia minor have (at most) mild anemia. This situation can very closely

resemble that with mild iron-deficiency anemia. However, persons with thalassemia minor have

a normal blood iron level (unless they are iron deficient for other reasons). No treatment is

necessary for thalassemia minor. In particular, iron is neither necessary nor advised.

Thalassemia major (Cooley's anemia): The child born with thalassemia major has two genes for

beta thalassemia and no normal beta-chain gene. The child is homozygous for beta thalassemia.

This causes a striking deficiency in beta chain production and in the production of Hb A.

Thalassemia major is, therefore, a serious disease.

At birth the baby with thalassemia major seems entirely normal. This is because the predominant

hemoglobin at birth is still fetal hemoglobin (Hb F). Hb F has two alpha chains (like Hb A) and two

gamma chains (unlike Hb A). It has no beta chains so the baby is protected at birth from the effects

of thalassemia major.

Anemia begins to develop within the first month after birth. It becomes progressively more and

more severe. The infant fails to thrive and often has problems feeding (due to easy fatigue from

lack of oxygen, with the profound anemia), bouts of fever (due to infections to which the severe

anemia predisposes the child) and diarrhea and other intestinal problems. Without treatment, the

spleen, liver and heart soon become greatly enlarged. Bones become thin and brittle. Heart failure

and infection are the leading causes of death among children with untreated thalassemia major.

The use of frequent blood transfusions and antibiotics has improved the outlook for children with

thalassemia major. Frequent transfusions keep their hemoglobin levels near normal and prevent

many of the complications of the disease. But repeated blood transfusions lead to iron overload

that can damage the heart, liver and other organs. Iron chelators can help rid the body of excess

iron, preventing or delaying problems related to iron overload.

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Thalassemia and Pregnancy:

Although fertility is reduced in a woman with transfusion dependent beta thalassemia,

pregnancy may be possible in some women. A few cases have been reported in literature. It is

necessary for the obstetrician to involve in the management, a medical team consisting of

hematologist, perinatologist and a genetic counselor. Because of the physiological changes in

pregnancy, the heart, liver, spleen and the endocrine system are particularly vulnerable. Anemia

becomes more pronounced and the requirement for transfusion increases.

During pregnancy, the enhanced maternal nutritional needs must be taken care of and

multivitamins are to be administered. But, iron should be avoided because of the concern of iron

overload. Preconceptional administration of folate, which must be continued at least until the

10th week of pregnancy is important to facilitate cell division. Vitamin C in the dose of 100-150 mg

helps in removal of iron. Further, thalassemic women are more at risk to develop insulin

dependent diabetes during pregnancy. Maternal and fetal morbidity may also result from

medications used and infections.

Genetic counseling is essential for assessment of fetal risk and to explain to the mother the role of

genetic testing in pregnancy.

In a population based study conducted in Israel, Sheiner et al observed that oligoamnios and fetal

growth restriction were significantly associated with â-thalassemia minor. No significant

differences were noted regarding perinatal outcomes such as birth weight, low Apgar scores,

congenital malformations, or perinatal mortality. Patients with â-thalassemia minor were more

likely to have cesarean deliveries than were the nonthalassemic parturients (16.9% and 12.2%,

respectively). However, while controlling for possible confounders such as IUGR,

oligohydramnios, and previous cesarean delivery, with another multivariate analysis with

cesarean delivery as the outcome variable, â-thalassemia minor was not found as an independent

risk factor for cesarean delivery. They concluded that the course of pregnancy of patients with

thalassemia minor, including perinatal outcomes, is favorable. Because higher rates of IUGR

were found, they recommended closer fetal surveillance for early detection of IUGR.

Screening and genetic testing for haemoglobinopathies:

Advances in genetic research that allow precise identification of mutations of the Hb genes make

the process of identifying couples at risk for having offspring with the hemoglobinopathies

increasingly important. Although universal screening is not recommended, all pregnant women

at the initiation of prenatal care are to be subjected to CBC counts with RBC indices. Taking

relevant history is important and particular attention must be paid to Kutchi Lohanas,

Gujaratis,Sindhis, Punjabis, Kojas and Marwaris and patients of Southeast Asian, Mediterranean,

or African descent. These patients can be referred for Hb electrophoresis. Those patients who

have anemia and reduced MCV (<80 m3) and normal iron study findings also must be referred for

hemoglobin electrophoresis. High pressure liquid chromatography, if available is of additional

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diagnostic value. The investigative profile of the thalassemic individual is more fully described in

the chapter on investigation of anemia in this monogram.

Test is offered to the partner of any carrier of hemoglobinopathies and any patient with elevated

HbA2 (>3.5%) to assess the risk to the fetus. If both partners are identified as carriers, DNA-based

tests are offered for the fetus.

Tests for prenatal diagnosis of thalassemia now include polymerase chain reaction (PCR) of fetal

DNA extracted from amniotic cells, of trophoblasts from chorionic villus sampling (CVS), and of

erythroblasts obtained from cordocentesis. Typically, CVS is performed at 10 weeks of gestation

to avoid limb reduction defects and cordocentesis is done after 19 weeks if confirmation is needed.

In many hemoglobinopathies, including sickle cell disease and most beta-thalassemias, point

mutations exist for which specifically designed oligonucleotide probes can be used, especially in

combination with knowledge of the patient's ethnicity. For some thalassemias, performing

indirect DNA testing by linkage analysis is still necessary.

Efforts to reduce the risks to the fetus incurred with invasive tests such as amniocentesis,

chorionic villus sampling, and cordocentesis have been made by acquisition of fetal cells from the

maternal circulation using magnetic cell sorting; however, this procedure is not standard. This

technique can only work in hemoglobinopathies in which the mutation has been identified

because only a small amount of fetal cells can be purified.

A fascinating advancement in prenatal diagnosis has been the development of a preimplantation

genetic diagnosis (PGD). In 1999, a team of reproductive endocrinologists reported single-cell

PCR and DNA analysis of embryos from a couple, both carriers for sickle cell disease, with

transfer of the genetically healthy embryos and subsequent delivery of healthy twins.

Preventive strategies:

The preventive programs are based on molecular diagnosis in high risk population. Screening is

carried out by testing blood indices and Hb chromatography antenatally and postnatally. PCR

and direct sequencing of DNA are done whenever required.

Premarital counseling plays a vital role. The incidence of thalassemia could be brought down if

carriers are discouraged from marrying another carrier. If both partners are diagnosed to be

carriers after marriage, they may be offered the option of donor insemination (AID) or adoption.

However, it may not always be practical to avoid biological offspring. In such couple at risk,

prenatal diagnosis and medical termination of pregnancy may be offered to prevent an affected

offspring.

Current Research on Thalassemia:

Scientists are working on better ways to remove excess iron from the body in order to prevent or

delay iron overload. They are developing and testing the effectiveness of oral iron-chelating

drugs, which could greatly simplify treatment of this disease.

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Development of an effective form of gene therapy may some day offer a cure for thalassemia.

Gene therapy may involve inserting a normal beta globin gene into the patient's stem cells, the

immature bone marrow cells that are the precursors of all other cells in the blood.

Another form of gene therapy may involve using drugs or other methods to reactivate the

patient's genes for fetal hemoglobin. After birth, natural genetic switches "turn off" production of

fetal hemoglobin and "turn on" production of adult hemoglobin. Scientists are seeking ways to

activate these genetic switches so that they can make the blood cells of patients with thalassemia

produce more fetal hemoglobin to compensate for their deficiency of adult hemoglobin. Initial

studies of rare individuals with genetic traits that allow them to produce only fetal hemoglobin

show that they are generally healthy, demonstrating that fetal hemoglobin can be a fine substitute

for adult hemoglobin.

Thalassemia has been cured using bone marrow transplants. However, this treatment is possible

only for a small minority of patients who have a suitable bone marrow donor. The transplant

procedure itself is still risky and can result in death. Improved bone marrow transplantation

methods may lead to wider use of the technique as a treatment for thalassemia.

Resources and References:

1. Thalassemia.com

2. irondisurders.org

3. ghr.nlm.nih.gov

4. Kilpatrick SS and Laros RK.1995.Thalassemia in Pregnancy.Clin. Obstet.Gynecol,

38(3):485-496.

5. Savona-Ventura C and Bonello F.Obstet.Gynecol.Surv.994 Feb; 49(2):129-37.

6. Sheiner E et al.Beta Thalassemia minor during Pregnancy.Obstet.Gynecol.2004;

103:1273-1277.

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Uncommon causes of AnemiaDr. Latha Venkataram, FRCOG

Consultant Maiya Hospital Bangalore

The obstetrician should be aware of the unusual anaemias which could complicate the

pregnancies leading to high maternal and perinantal morbidity and mortality. Chronic Anaemia

and Anaemias resistant to treatment in a women should be investigated further in coordination

with a Hematologist. Pre pregnancy counseling is an important aspect of care. Management

plans during pregnancy should be drawn with the involvement of hematologist. Though there is

an extensive list of unusual forms of anemia, few of them relevant to pregnancy have been

mentioned here.

Special problems in Pregnancy Comment Treatment

An enlarged spleen traps and destroys too many red blood cells

Splenectomy not advisable in pregnancy

Symptoms tend to be mild; often an enlarged spleen reduces the number of platelets and white blood cells

Treatment is aimed at the disorder that has caused the spleen to enlarge. Sometimes the spleen must be removed surgically

Worsening of anaemia in pregnancyErythropoietin not contraindicatedDialysis not contraindicatedAnticoagulant prophylaxis since more prone for thromobosis

Genetic mutation in haemopoietic stem cells affecting the red cells, granulocytes, platelets. The immune system destroys red blood cells in a sudden (paroxysmal) way, not just at night

Ferttility rate low. Abortions increased. MMR increased. Prone for thrombosis, infection, marrow aplasia in pregnancy.O.C.P contraindicated. Iucd contraindicated if granulocytes & platelets low

Can cause severe stomach cramps and clotting in the large veins of the abdomen like hepatic or mesenteric and lower limb veins

Corticosteroids relieve symptoms, but no cure is available. People with blood thrombosis need therapeutic doses of anticoagulant. Bone marrow transplantation may be needed long term

Hyperhaemolytic & aplastic crisiscan occur. Folic acid supplementation recommended

An inherited disorder that can also cause bone abnormalities, such as a tower-shaped skull and extra fingers and toes

Treatment is usually not needed, but severe anemia may require removal of the spleen

Idiopathic, medications, infections, toxins. Pregnancy rarely induces aplastic anaemia. Spontaneous resolution might occur after delivery

Termination of pregnancy recommended. Aplasia can rapidly deteriorate

The G6PD enzyme is missing from red blood cell membranes. Without the enzyme, red blood cells are more likely to break apart

Heterozygous women may havesevere anaemia. Folic acid supplementation recommended. May need transfusions

An x linked inherited disorder that almost always affects only males. About 10% black males and a smaller percentage of white people of Mediterranean origin have the disorder

Anemia can be prevented by avoiding the situations or substances (fever, diabetic crisis, aspirin, vitamin K, fava beans) that trigger it

Primary or secondary-drugs, infections, SLE, neoplasia. Pregnancy itself might cause haemolytic anaemia

Steroids to be continuedTransfusion may be requiredNeonatal anaemia may occurRecurs in subsequent pregnancy if the condition appears in pregnancy

Cause Mechanism

Enlarged spleen(idiopathic)

Anaemia secondary to renal disease

CRF

Paroxysmal nocturnal hemoglobinuria

Hereditary spherocytosis

Autosomal dominant red blood cells become misshapen and rigid, getting trapped and destroyed in the spleen

Aplastic anaemia

G6PD deficiency

Autoimmune haemolytic anaemia

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INVESTIGATIONS IN ANAEMIA WHAT?

WHEN? AND WHY?

Dr.Jayanthy.T MD

Asst. Professor, Dept. of OBGKempegowda Institute of Medical Sciences, Bangalore.

There are spectrum of investigations done in case of anaemia. Plan of investigations for anaemia

is done 1. To confirm anaemia and assess severity of anaemia2. To investigate for type of anaemia and cause for anaemia

1. Screening & Diagnostic tests:

a. Haemoglobin estimation.(Hb) Normal values

Men 14 – 18 gm/dl

Women 12 – 16 gm/dl

Pregnancy 10.5 – 11 gm/dl

b. Peripheral blood film examination

c. Red cell indices Normal values

Packed Cell Volume (PCV) Women 35 – 45%

Men 40 – 52%

Mean Corpuscular Volume (MCV) 75 – 90 fl

Mean Corpuscular Haemoglobin (MCH) 27 – 31pg

Mean Corpuscular Haemoglobin conc (MCHC) 30 – 35 g/dl

d. Leucocytes and platelet count

e. Reticulocyte count 1 - 2%

2. Confirmatory Tests:

a. Bone marrow examination.

b. Biochemical tests.

c. Special tests to diagnose specific conditions.

Relevant Investigations specific to type of anaemia.

IRON DEFICIENCY ANAEMIA

1. Hemogolobin Estimation:

Reduced haemoglobin. It is a late manifestation. It is preceded by depletion of iron stores, then

reduction in Serum Iron. Though Hb decrease is a late sign, it is a simplest and practical test

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2. Peripheral Blood Smear:

Microcytic, Hypochromic RBC's. Anisocytosis, Poikilocytosis, Target

cells are seen. Reticulocytes may be normal or decreased. The

differential diagnoses are Thalassemia and Pyridoxine deficiency

anaemia.

3. Red Cell indices:

PCV is decreased.

MCV, MCH and MCHC are reduced.

3. Bone Marrow Examination:

It may not be required to make a diagnosis of iron deficiency anaemia. However, when done it

shows erythroid hyperplasia and micronormoblastic reaction. There is reduction or absent

stainable iron depending on iron depletion.

5. Biochemical Tests:

a. Serum ferritin – is a first indicator of iron deficiency anaemia normal value is 15 – 300

ìg/dl. Here it may be < 12ìg/dl.

b. Serum iron is reduced to < 30ìg/dl. Normal value 50 - 150ìg/dl.

c. Total iron binding capacity (TIBC) is increased to 500ìg/dl and TIBC saturation may be

< 15%. Normal value is 250 – 450 ìg/dl.

d. Red cell protoporphyrin level – it is a sensitive indicator of iron deficient erythropoiesis.

It may be increased to 100 ìg/dl. Normal is 20 - 40ìg/dl.

e. Serum Transferrin Receptor (Tf R) – is reliable for assessing celluar iron states. In iron

deficiency there is a three fold increase in Tf R. Normal level is 4 – 9 ìg/dl. This,

combined with serum ferritin gives a complete picture of iron status.

f. Other tests to rule out chronic blood loss should be done after detailed history and

examination for example urine microscopy for haematuria, stools for ova, etc.

SIDEROBLASTIC ANAEMIA.

It can be hereditary or acquired, and findings differ in both.

a) Hereditary

1. Hb is reduced

2. Hypochromic microcytic cells are seen, some times a dimorphic picture.

3. MCV and MCH are reduced.

4. Serum iron is increased.

5. TIBC shows complete saturation.

6. Bone marrow shows ring sideroblasts, mature erythroblasts and increased stainable

iron.

b. Acquired

1. Hb is reduced.

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2. PBS – dimorphic picture, target cells, stippled cells and siderocytes, Pelger Huet

neuetrophils.

3. MCV is increased but MCH is decreased.

4. Serum Iron and ferritin is increased.

5. TIBC is decreased.

6. Bone marrow shows hyperplastic and ring

sideroblasts, Pappenheimer granules.

MEGALOBLASTIC ANAEMIA

Folic acid deficiency

a. Hb decreased.

b. PBS – Macrocytes, anisopoikilocytes, Cabot'srings, tear

drop cells, hypersegmented neutrophils (at least three

cells having more then five nuclear segments), basophilic

stippling, Howell Jelly bodies. In late stages there may be

neutropenia and thrombocytopenia.

When there is associated iron deficiency there may be many microcytic cells along with

macrocytes

c. MCV is more then 100fl. MCH is increased to more then 35pg but MCH is normal.

d. FIGLU Test (Formiminoglutamic Acid) – In folate deficiency FIGLU is increased in

urine and it is non specific and not very useful.

e. Bone marrow shows dyserythropoiesis, megaloblasts in erythroid series,

myeloid /erythroid ratio falls to 1:1.

Special tests:

a. Serum folate levels – It will indicate levels of folate for preceding few days only. It is

transient and will alter with folic acid administration. Normal is more than 5ng/ml.

b. Red cell folate levels – Normal is 160 to 640ìg/l. Reduction in this is a better indicator of folate

deficiency.

2. Vitamin B (Cobalamin) deficiency12

This may be a rare entity but when ever there are clinical features and folic acid levels are normal

in megaloblastic anaemia, cobalamin deficiency should be suspected.

Red cell indices, peripheral blood picture and bone marrow are similar to folate deficiency

anaemia, but here folate levels are normal.

Special tests:

1. Serum vitamin B assay :12

a.Microbiological assay using Euglena gracilis or Lactobacillus Leichmani.

b.Radioisotope assay

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Normal is 200 to 900 pg/dl less then 100pg/dl indicates deficiency..

2. Increased levels of both Serum Methyl malonic acid and homocystine.

3. Increased urinary excretion of Methyl malonic acid.

4. Radioactive vitaminB absorption test 12

a. Radioactivity in faeces.

b. Radioactivity in urine (Schilling test)

c. Radioactivity in liver

d. Radioactivity in whole body

e. Radioactivity in plasma

Schilling test is commonly done. This helps in knowing intrinsic factor deficiency.

Megablastic anaemia is seen in various other conditions like chronic liver disease, rheumatoid

arthritis etc. Depending on the clinical manifestations, specific investigations have to be done.

3. Dimorphic anaemia

In India and other developing countries patients manifest multiple deficiencies like iron, folic

acid, cobalamin, pyridoxine and other vitamins. In such cases there is a dual population of

macrocytic and microcytic hypochromic RBC's. In some cases macrocytic hyprochromic cells are

seen.

4. Haemolytic anaemia

In Haemolytic anaemias haemolysis is a common feature. In most of the conditions, tests for

haemolysis and findings are similar. Therefore tests common to all types of haemolytic anaemias

is discussed first followed by specific investigations in each type of disorders.

Evidences of haemolysis.

Increased breakdown of haemoglobin causes

a. Reduced haemoglobin - sometimes Hb may be normal.

b. Hyperbilirubinemia. (unconjugated)

c. Reduced plasma haptoglobin and haemopexin.

d. Increased plasma LDH.

e. Increased urinary urobilinogen.

f. Increased reticulocyte count.

Evidences of Intravascular haemolysis:

a. Haemoglobinuria and haemoglobinemia.

b. Haemosiderinuria.

c. Methaemoalbuminemia.

The specific tests for each type of haemolytic anaemias is discussed further.

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I. Thalassemia

This is quite common in our country and is a differential diagnosis for microcytic hyprochromic

anaemia.

a. Reduced Hb.

b. PBS – Microcytic, hypochromic red cells. Moderate to

severe anisocytosis and poikilocytosis ,nucleated RBC's,

plenty of target cells, tear drop cells ,granular

cytoplasmic inclusionbodies , polychromasia

reticulocytosis ismarked and more than 10%

c. MCV and MCH is markedly reduced . MCHC is normal.

d. Serum iron level is markedly increased.

e. Serum ferritin is 300 to 3000 ng/dl.

f. TIBC saturation is more than 70%.

g. Bone marrow shows micronormoblastic reaction, erythroid hyperplasia, striking

basophilic stippling and increased iron deposition and ring sideroblasts.

Other Tests

1. Decreased osmotic fragility

2. Alkali denaturation tests – This test is based on the factor that normal adult haemoglobin gets

denatured when alkali is added but fetal haemoglobin is resistant and not destroyed. This

test reveals increased HbF levels in thalassemia major.

3. Hb electrophoresis. In thalassemia minor, HbH is present in adults and Hb Barts in infants.

Electrophoresis using starch agarose gel at PH 8.6 is useful in diagnosis, which shows

increased HbF and HbA2.

4. Genomic study of DNA by Southern blotting of endonuclease is a very useful test. Prenatal

diagnosis of Thalassemia is very useful.

II. SICKLE CELL ANAEMIA:

1. Hb reduced.

2. PBS – normochromic, normocytic cells, fragmented RBC's, anisopoikilocytosis, target cells

and sickle cells are seen. Reticulocytosis is present.

3. MCV and MCH are normal. MCHC is increased.

4. Bone marrow shows erythroid hyperplasia.

Other Tests:

1. ESR is decreased.

2. Osmotic fragility is decreased.

3. Sickling test is positive. It can be demonstrated by adding Sodium metabisulphite or ascorbic

acid. Sickledex, a proprietary product is available. It detects HbS by precipitation of

deoxygenated HbS. It is rapid and reliable.

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4. Life span study of RBC's shows decreased survival.

5. Hb electrophoresis shows increased HbS.

II. HEREDITARY SPHEROCYTOSIS

1. Hb is reduced.

2. PBS – Spherocytes lacking central pallor, reticulocytosis and thrombocytopenia is seen.

3. MCV is normal, sometimes it may be decreased. MCH is normal. MCHC is raised.

4. Increased osmotic fragility.

5. cDNA – Genomic DNA analysis for molecular diagnosis may be helpful.

III. HERDITARY ELLIPTOCYTOSIS

1. Haemoglobin is reduced.

2. PBS – Ovalocytes or Elliptocytes are seen and constitute more than 50% of the cells.

3. MCV and MCH are normal.

4. Osmotic fragility is increased.

IV. CONGENITAL HAEMOLYTIC ANAEMIA

1. Hb is reduced.

2. PBS – Polychromasia, basophilic stippling, Heinz bodies, macrocytes are seen.

3. MCV and MCH is increased.

4. Enzyme assays should be done to detect various enzyme deficiencies.

a. G6PD deficiency – 1. Brilliant cresyl blue test.

2. Heinz body test.

3. Fluorescent spot test.

4. Enzyme assay.

b. Phosphokinase deficiency.

c. Pyruvate kinase deficiency.

V. ACQUIRED HAEMOLYTIC ANAEMIA

1. Hb may be normal in acute phase.

2. PBS – Polychromasia, basophilic stippling and reticulocytes.

3. Osmotic fragility test is increased.

4. Direct Coomb's test may be positive.

5. Serological test for antibodies in serum.

6. Urine test may show increased levels of coproporphyrin.

7. Other tests to know the cause may be done depending on the clinical features for eg. Malarial

parasites in malaria.

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VI. PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA

1. Hb is decreased to less than 5gm/dl.

2. PBS – dimorphic anaemia.

3. Total leucocytes and platelets are reduced.

4. Reticulocytosis is seen.

5. Bone marrow shows erythroid hyperplasia.

6. Urine – Hb casts, haemosiderinuria is a constant feature

VII. APLASTIC ANAEMIA:

1. Hb is decreased.

2. PCV is decreased

3. Total leucocytes count is decreased. Differential count shows marked neutropenia.

4. Platelets are decreased.

5. PBS – usually normal cells are seen sometimes macrocytosis, anisocytosis and poikilocytosis

is seen.

6. Bone marrow is hypoplastic or aplastic, shows numerous spicules with empty fatty spaces.

Dyserythropoietic lymphocytes, plasma cells and macro phages. Relatively few

haemopoietic cells.

7. Serum Iron is increased.

8. Plasma erythropoietin is increased.

9. Coagulation profiles are abnormal.

Lastly, anaemia may be a feature in leukemias. Here leucocytes and reticulocytes are increased.

Normochromic RBC's are seen.

Bibliography:

1. Cecils text book of Medicine.

2. de Gruchy's clinical haematology in medical practice.

3. Harrison's text book of Principles of internal medicine.

4. Text book of Haemotology – basic principles and practice by Hoffman co.et al.

5. Blood – Principles to practice of Haematology by R.I. Hand , S.Lux and T.P. Russel.

6. Text book of Medical laboratory technology by Ramnik Sood.

7. Practical pathology Dr.U.Chaturvedi and T Singh.

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MANAGEMENT OF IRON DEFICIENCY

ANEMIA IN PREGNANCY

Dr. Jyothika A. Desai

Dr. P.R. Desai Hospital, Bangalore

Anaemia is not a disease. It is a sign of an underlying disorder.Treatment, therefore, must be

preceded by an accurate diagnosis of the cause and the type of anemia.

General Measures

Diet

A basic knowledge of iron metabolism in the body will help us in understanding the mechanisms

by which the iron supplements help in correcting the deficiency.

Iron absorption

Healthy people absorb around 5 to 10 percent of the iron in their daily diets. Absorption is highest

in childhood, and reduces with age. Iron is present in animal foods in organic 'heme' form and in

plant foods in inorganic 'nonheme' form. The heme and nonheme forms of iron are absorbed by

different mechanisms. About 20 to 30 percent of heme iron is absorbed compared to only 2 to 5

percent of nonheme iron. Heme iron is broken down by pancreatic enzymes and is absorbed. Its

absorption is unaffected by food factors. Non Heme iron must be in ferrous form to be absorbed

and the hydrochloric acid of the stomach converts ferric iron to ferrous iron. Iron absorption is a

slow process, taking between two and four hours. Iron levels in the body are regulated by

absorption, rather than by excretion and low body iron levels lead to improved absorption. In

cases of iron deficiency absorption efficiency increases to around 10 to 20 percent. Various food

factors affect iron absorption and the overall amount of iron absorbed from a meal will depend on

the interactions between these factors.

Enhancers

Low body stores Full body stores

Hydrochloric acid in the stomach Reduction in stomach acid

Vitamin C Tannins (e.g. in tea)

Sugars Oxalic acid (e.g. in spinach)

Haem iron Phytic acid (in dietary fibre)

Calcium and phosphorus in milk

Enhancers and Inhibitors of Non heme iron absorption

Inhibitors

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Food Fortification is a preventive measure that aims at improving and sustaining iron nutrition

on a permanent basis.Cereals, sauce, sugar, curry powder and salt are some of the items which

are fortified with iron.

Treatment of Hookworm infestation

a) Albendazole 400mgs | only in the

b) Mebendazole100 mgs twice daily for 3 days |

c) Avoiding walking barefoot to prevent Hookworm infestation

Aims of Therapy

a) To raise the Hb level

b) To replenish the iron stores

Choice of Therapy

depends upon

a) Severity of Anaemia

b) Duration of pregnancy and

c) Associated complicating factors

Principles of iron therapy

First introduced by Dr.Pierre Blaud in the 19th century.

1. Inorganic iron salts should be given orally

2. A raise in Hb concentration of about or > 0.5 gm per 100cc daily is considered a positive

response

3. Once the Hb concentration has risen to the normal range, iron therapy should be given for

a further period of 3 months to replenish the iron stores.

4. Response to parenteral iron is almost similar to oral iron- in the absence of malabsorbtion.

5. Bone marrow response and erythroid hyperplasia are seen within 48 hrs of starting

therapy and iron stores are replenished within 3 months.

Iron Therapy

can be

a) oral or

b) parenteral

Oral iron

Iron is best absorbed in the ferrous form. It is available as various salts -gluconate,

fumarate,sulphate, succinate, etc. Ferrous Sulphate is available as a 200mg tablet with 60 mgs of

elemental iron along with traces of zinc and magnesium. The therapy is started with 1 tablet

2nd or 3rd trimesters

only in the 2nd or 3rd trimesters

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thrice daily with food, followed by gradually increasing the dosage to 2 tablets thrice a day. Once

the Hb has reached normal values, it can be maintained at 1 tablet a day for 3 months to replenish

the iron stores.

Recommended daily requirement of iron:

For prophylaxis, the Govt of India recommends 100 mgs of elemental iron with 0.5 mg of Folic

Acid, but for treatment, more than 180 mgs of elemental iron with 5 mgs of Folic Acid is

recommended.W.H.O recommends 30-60 mgs of iron be given daily to pregnant women with

normal iron stores and 120-240 mgs to those with none.

Drawbacks of oral iron therapy

a) Gastro-intestinal side effects …seen in 10% of women. It is dose related and is less when the

iron is <100 mgs per day. It depends upon the amount of ionic iron - the absorbable form of

iron that comes in contact with the gastro-intestinal mucosa. The common symptoms are

epigastric distress, nausea, vomiting, constipation, diarrhoea etc.They can be avoided by

1) Starting with a small dose and gradually increasing it,

2) By changing the preparation. Carbonyl iron and Hb preparations are better tolerated

3) Giving it with meals. Slow release preparations, which are generally more expensive are said

to be relatively free from side effects. This is perhaps so because much of the iron is not

released at all or is unabsorbed and excreted unchanged.

b) Unpredictable absorption…therefore cannot be depended upon when a quick response is

desired. Iron absorption is diminished by antacids, oxalates, phosphates in bread, milk and

cereals, and tannins in tea. Iron absorption is increased by…ascorbic acid, lactate, amino-

acids, sugar, citric acid, HCL in the stomach, meat etc.

Response to therapy is evidenced by

a) Rise in Hb level…A rise in 0.1gm% or more daily is considered a positive response. Hb

response is greater in the first few weeks of therapy and is proportional to the severity of

anaemia.A rise in Hb concentration of 1gm% per wk in the non-pregnant state or 0.8gm%per

wk in pregnancy can be expected with adequate iron treatment whether oral or parenteral.

b) Haematocrit comes to normal

c) Reticulocytosis within 7-10 days

d) Subjective symptoms increased sense of well-being, improved appetite,etc

If no significant improvement is evident clinically and haematologically within 3 wks of

therapy, the diagnosis should be reviewed.

Causes of failure of improvement

a) Noncompliant patient who does not take the prescribed dosage

b) Defective absorption either because of the preparation or because of coexisting gastro-

intestinal disorders

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c) Incorrect diagnosis of the type of anaemia

d) Concurrent blood loss due to hookworm infestation or bleeding piles

e) Coexistent undiagnosed folate deficiency

f) Inhibition of erythropoiesis due to infection

Contraindications to Oral iron therapy

a) Intolerance to oral iron

b) Severe anaemia in advanced pregnancy

Indications for Parenteral iron therapy

a) Intolerance to oral therapy

b) Non compliant patient

c) Severe anaemia in advanced pregnancy

d) Malabsorbtion syndrome

Advantages of Parenteral therapy

a) Certainty of iron administration

b) Replenishment of iron stores

Routes of administration

a) Intramuscular

b) Intravenous

Calculation of total iron deficit:

Total iron deficit in adult patients may be estimated using one of the following equations (Hbt =

target Hb level; Hbo = observed or actual Hb level; Bwt = body weight)

Total Dose (mg) = 50 {0.0442 Bwt (Hbt - Hbo) + (0.26 Bwt) }

Total Dose (mg) = 2.4 Bwt (15 - Hbo) + 500

Contraindications and Precautions:

v Parenteral iron supplementation is ineffective in aplastic or hypoplastic anemia and acute

leukemia.

v Parenteral iron supplementation is contraindicated in early pregnancy, in patients with liver

disease or acute renal failure.

v IV iron products must be used with caution to minimize acute adverse reactions. An

anaphylaxis management kit should be at hand.

v Conservative estimates of iron deficit should be used to avoid iron overload.

v Measures of iron status (ferritin, total iron binding capacity, & transferrin saturation) and red

blood cell indices must be checked periodically to reevaluate the patient's need for additional

iron supplementation. Parenteral iron should not be administered to patients with ferritin >

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800 ng/mL or transferrin saturation > 50%.

Intramuscular iron

Preparations available are Iron-Dextran (Imferon), (Ferri) Iron Sorbitol Citric Acid Complex

(Jectofer)

All preparations contain 50 mgs of elemental iron in 1 cc. Oral iron should be suspended 24 hrs

before starting parenteral iron.

The dose of Intramuscular iron calculated as per the formula which is the same as for Intravenous

iron. The total dose of Iron Sorbitol CAC is adjusted because 30% is excreted in the urine. Test

dose of 1cc is given followed by daily or alternate day IM injections in doses of 2cc.

Drawbacks

Local - pain, pigmentation, abscess formation. Few precautions taken while injecting can prevent

these local reactions like utilizing the Z technique, injecting air or saline before withdrawing the

needle and not massaging the injection site.

Systemic

a) Diarrhoea, nausea, vomiting, fever, lymphadenopathy

b) Anaphylactic reaction in 2 % of patients

c) Arthralgia, especially in rheumatoid arthritis.

d) Haemolysis

Intravenous iron The various preparations available are Iron Dextran (Imferon, Ferri), Iron

Hydroxide Sucrose Complex (Encifer) etc.Intravenous iron can be given as a single or multiple

dose without dilution or diluted as a total dose infusion. A test dose of 0.5 cc diluted with 4-5 cc of

the patient's blood is injected slowly and patient observed for 1 hour. If there is no reaction, upto 5

cc can be given slowly as a single bolus at the rate of 1cc/minute.

Total dose infusion

The total dose calculated is diluted in 1 litre of saline or dextrose. Saline is preferred as phlebitis is

less often seen. Not more than 2500mgs can be given in 1 litre.If the total dose is more than

2500mgs or 50 cc (1cc=50mg), then the total dose should be infused on 2 consecutive days.

The formulae for calculating the total dose are as follows…

a) 2.3 x wt in kgs x (15—pt's Hb% in gms) +1000mgs(for stores)

b) 0.3 x wt in lbs x (100—Hb %) + 50% for stores

c) A simple method is to give 250 mgs of elemental iron for each gm of Hb below the normal (14

gms) and add 50 % more for replenishment of iron stores.

Technique for Total dose infusion

Precautions as for a blood transfusion should be taken. The drip rate should be about 10

drops/minute for the first 20 minutes. It can be later increased to 40 drops/minute. Any reaction

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like rigors, chest pain etc, calls for immediate suspension of the drip.

Iron Hydroxide Sucrose Complex is not licensed for total dose infusion and can be given as 5cc

(vial contains 5cc with 20mg/cc) slow IV or as a short infusion for 15 minutes with N.S for 1-3

doses per week. It has excellent tolerance with few complications.

Advantages of Total dose infusion

a) It eliminates repeated and painful IM injections

b) The treatment is completed in 1 day

c) Expenditure is less than for the IM course

Blood transfusion in pregnancy

Considered only in severe anemia close to delivery where packed cells transfusion is given. The

other major indication for blood transfusion in pregnancy is in management of acute blood loss as

in APH /PPH

Antenatal management of a case with anaemia

The prognosis is good if anaemia is detected and treated in time. Therapeutic dose of oral iron

should be started after the 14th week. The patient should be seen more often to detect and manage

the complications of anaemia such as Heart failure, Preterm labour etc. Fetal growth to be

monitored carefully as IUGR is commonly seen. Betamimetics should be given with caution in

patients with anaemia and preterm labour to avoid the risk of pulmonary oedema.

Management during labour

The aim is to have a normal delivery. Ideally, anaemia should have been treated during

pregnancy but in the event of a patient arriving in labour with untreated anaemia then in the

First stage

a) The patient should have back rest or should be in any other comfortable position

b) Pain relief should be offered

c) O2 inhalation if patient is breathless. This will also reduce the risk of fetal hypoxia.

d) Prophylactic antibiotics may be required.

e) Digitalisation if in failure with severe anaemia

Second stage

Should be shortened by Outlet forceps /vacuum. Prophylactic oxytocics should be given to

curtail blood loss.

Third stage

Should be managed actively. Significant blood loss should be replaced with fresh packed cells.

Puerperium

The problems faced are:

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v Subinvolution of the uterus due to infection

v Poor lactation

v Thromboembolism

Oral iron should be given for at least 6 months.

Contraception

Spacing of pregnancies is very important for an anaemic woman. Progesterone only preparations

are preferred. In a non lactating woman COCs are a good alternative since blood loss during

menstruation is minimal. IUCD may be considered if there is no history of menorrhagia.

To reiterate, an anaemic woman must use an effective method of contraception and avoid

pregnancy for at least 2 yrs to give time for her iron stores to be replenished.

Bibliography

1. Scott DE, Pritchard JA: Iron deficiency in healthy young college women. JAMA 1967;

199:897-900.

2. Roszkowski I, Wojcick J, Zaleska K:Serum iron deficiency during the third trimester of

pregnancy: Maternal complications and fate of the neonate. Obstet Gynecol 1996; 28:820-

825.

3. Thompson WB: Comparison of tests for diagnosis of iron depletion in Pregnancy. Am J

Obstet Gynecol 1988; 159:1132-1134.

4. Goepel E, Ulmer HU, Neth RD: Premature labour contractions and the value of serum ferritin

during pregnancy. Gynecol Obstet Invest 1988; 26:265-273.

5. Stein ML, Gunston KD, May RM: Iron dextran in the treatment of iron deficiency anemia of

pregnancy: Haematological response and incidence of side effects. S Afr Med J 1991; 79:195-

196.

6. Taylor DJ, Mallen C, Mc Dougall N, Lind T. Effect of iron supplements on serum ferritin

levels during and after pregnancy. Br J Obstet Gynaecol 1982; 89:1011-17.

7. World Health Organisation. Nutritional Anaemias. WHO, Geneva, 1972.

8. De Leeuw NK, Lowenstein L, Hsieh YS. Iron deficiency and hydremia in normal pregnancy.

Medicine (Baltimore) 1966; 45:291-315.

9. World Health Organisation. Prevention and management of severe anemia in pregnancy.

Report of a Technical Working Group, Geneva, 20-22 May 1991. Maternal Health and safe

Motherhood Programme. WHO, Geneva, 1993.

10. Chisholm J. A Controlled clinical trial of prophylactic folic acid and iron in deficiency. J

Obstet Gynaecol 1966; 73:191-6.

11. Rios E, Lipschitz DA, Cook JD Smith NJ. Relationship of maternal and infant iron stores as

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assessed by determination of plasma ferritin. Pediatrics 1975; 55:694-9.

12. Halleberg I, Ryttinger L, Solvell L. Side effects if oral iron therapy. Acta Med Scand 1966; 459

(Suppl):3-10.

13. Stein ML, Gunston KD, May RM. Iron dextran in the treatment of iron

Deficiency anaemia of pregnancy. Haematological response and incidence of side effects. S

Afr Med J 1991; 79:195-6.

14. AI-Momen AK, Al-Meshari A et al. Intravenous iron sucrose complex in the treatment of

iron deficiency anaemia during pregnancy. Eur J

Obstet Gynecol Reprod Biol 1996; 69; 121-4.

15. Anonymous. Do all pregnant women need iron? Br Med J 1978; ii: 1317.

16. Schwartz WJ, Thurnau GR. Iron deficiency anaemia in pregnancy. Clin Obstet Gynecol

1995; 38:443-454.

17. Turmen T, Abou Zahr C. Safe motherhood. Int J Gynecol Obstet 1994; 46:145-153.

18. Sharma JB, Medical complications in pregnancy. In:Sharma JB. (ed) The Obstetric Protocol,

1st edn. Delhi: Jaypee Brothers, 1998; 78-98.

19. Letsky E. Blood Volume, haematinics, anaemia. In: de Swiet M. (ed)

Medical Disorders in Obstetric Practice, 3rd edn. Oxford Blackwell, 1995; 33-60.

20. World Health Organisation. Report of a WHO Group of Experts on Nutritional Anaemias.

Technical report series no. 503, Geneva: WHO, 1972.

21. Abel R, Rajaratnam J, Sampathkumar V. Anaemia in pregnancy. Impact of iron, Deworming

and IEC, RUSHA Dept. Tamil Nadu: CMC Vellore, 1999.

22. Indian Council of Medical Research. Evaluation of the National Nutritional Anemia

Prophylaxis Programme. Task Force Study. New Delhi: ICMR, 1989.

23. Hulten LE, Gramatkovski A, Gleerup A, Hallberg L. Iron absorption from the whole diet.

Relation to meal composition, iron requirements and iron stores. Eur J Clin Nutr 1995; 49:

794-808.

24. Hallberg L, Bjorn – Rassmussen E. Determination of iron absorption from whole diet. A new

tool model using two radiation isotopes given as haem and non-haem iron. Scand J

Haematol 1972; 9:193-197.

25. Stolzfus R, Dreyfuss ML, Guidelines for the use of iron supplements to prevent and treat iron

deficiency anaemia. Geneva: INACG, WHO, UNICEF, 1998.

26. Sharma JB, Arora BS, Kumar S, Goel S, Dhamija A. Helminth and protozoan intestinal

infections: an important cause for anemia in pregnant women in Delhi, India. J Obstet

Gynecol Ind 2001:51(6):58-61.

27. Sloan NL, Jordan EA, Winikoff B. Does Iron supplementation make a Difference? Mother

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Care Project, 15 Arlington, VA, USA. 1992.

28. Milman N, Bergholt T, Byg KE Eriksen L, Graudal N. Iron status and iron balance during

pregnancy. A critical re-appraisal of iron supplementation. Acta Obstet Gynecol Scand 1999;

78:749-757.

29. Sharma JB. Iron deficiency anaemia in pregnancy-still a major cause of maternal mortaility

and morbidity in India. Obs Gynae Today 1999: IV: 693-701.

30. Rusia UN, Madan N Agarwal N, Sikka M, Sood SK. Effect of maternal iron deficiency

anaemia on fetal outcome. Ind j Pathol Microbiol 1995; 38:273-279.

31. Mahomed K. Routine iron supplementation during pregnancy. (Cochrane Review) The

Cochrane Library, Issue 2. Oxford; Update Software 1998.

32. Ridwan E, Schlultink W, Dillon D, Gross R. Effects of weekly iron supplementation on

pregnant Indonesian women are similar to those of daily supplementation. Am J Clin Nutr

1996; 63:884-890.

33. Bhatt RV. Poor iron compliance – the way out. J Obstet Gynecol Ind 1997; 47:185- 190.

34. Atukorala T, deSilvla LD, Dechering WH, Dassenaeike TS, Perera RS. Evaluation of

effectiveness of iron folate supplementation and antihelminthic therapy against anaemia in

pregnancy- study in the plantation sector of Sri Lanka. Am J Clin 1994; 60:286-292.

35. Bhatt RV. Anaemias in pregnancy: early diagnosis and treatment. J.Ind Med Assoc 1995;

93:80-82.

36. Indian Council of Medical Research. Field Supplementation Trial in Pregnant Women with

60 mg, 120 mg and 180 mg of Iron with 500 ugm., of Folic Acid . New Delhi: ICMR, 1992

37. Sood SK, Madan N, Rusia U, Sharma S. Nutritional anaemia in pregnancy and its health

implications with special reference to India. Ann Nati Acad Med Sci 1989; 25:41-50

38. Prema K. Anaemia in pregnancy. In:Ratnam SS, Rao KB, Arulkumaran S. (eds) Obstetrics

and Gynaecology,. Vol. I Madras: Orient Longman,1992; 42-53.

39. Basu SK. Administration of iron dextran complex by continuous intravenous infusion. J

Obstet Gynaecol Br Cwlth 1965; 72:253-258

40. Blot I, Papiemik E, Kaltwasser JP, Werner E, Techernia G. Influence of routine

administration of folic acid and iron during pregnancy. Gynecol Obstet Invest 1981; 12:294-

304.

41. Swalin RA, St. Clair L. The role of folic acid in deficiency status and prevention of disease. J

Fam Pract 1997; 44:138-144.

42. Chanarin L. Folate deficiency in pregnancy. In: Chanarin I (ed). The Megaloblastic

Anaemias, 3rd edn. Oxford: Blackwell, 1990:140-148

43. Iyengar L. Folic acid requirements of Indian pregnant women. Am J Obstet Gynecol 1971;

111: 13-16.

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Eating right, right from now!

Dr. Sita Bhateja

Sita Bhateja's Nursing Home, Bangalore

Anemia is the commonest cause of poor health amongst Indian women. There are so many causes

of this malady but we shall talk only about the nutritional anemia. About 60% of the women have

hemoglobin less than 10 gms/dl. They are not always from the lower socio-economic class. This is

also prevalent amongst the middle and high socio-economic strata of women in our country. This

is basically due to poor knowledge about nutrition.

Causes of poor nutrition

1. Lack of information regarding balanced diet, specifically the anti-anemic factors.

2. Stereotype of menu – same quality of food day after day.

3. Eating wrong type of food, what is more commonly known as junk food! Foods which are

uncooked, cold aerated drinks, white flour preparations, and sweet, sugar coated food items

like chocolates are the types of food which have poor nutritional value. These food items kill

appetite and are habit-forming.

4. In case of pregnant women and adolescents the requirement is much more. This must be

taken into account by the individuals while they are preparing their food and they must be

educated about their diet by the treating doctors.

5. If there is heavy blood loss due to heavy menstrual cycle, bleeding piles or any other cause for

chronic blood loss, it will cause anemia.

In early months of pregnancy women develop anemia due to vomiting which causes loss of

nutritional products from the diet.

There should be a balanced diet. Many of these dietary factors are inter-dependent for absorption.

Variety of food is the key to getting all the ingredients which would prevent nutritional anemia.

Chronic deficiency of hemoglobin leads to poor vitality and fatigue. Essential ingredients for

preventing anemia are:

Iron

Folic acid

Vitamin B12

Vitamin C

Trace elements Zinc, Chromium, Selenium.

The chart shows what is the requirement and in which food they are to be found.

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The modern educated woman is aware of the problems. Nowadays some of them come for

preconception checkup. That is the best time to diagnose pre-existing anemia and cure it well

before the pregnancy. This will ensure proper oxygen supply to the fetus from the very beginning.

Chronic oxygen deficiency due to maternal anemia will produce poor pregnancy outcome.

The modern diet is very deficient in folic acid because it is destroyed by cooking. Therefore some

fresh green raw vegetables will be desirable. Eg. Lettuce, sprouted beans. In addition folic acid

supplement is very necessary. Vitamin B12 is an ingredient which is found mostly in non-

vegetarian diet. Lot of people in India are vegetarians. It is necessary to supplement the diet with

B12 tablets.

Vitamin C is another unstable ingredient. It promotes iron absorption. Citrus fruits and amla are

good sources. Unpeeled potatoes are a good source of vitamin C. Other trace elements may not be

easily available in diet. Therefore the simplest solution is to supplement these with tablet or

injections.

Calories may be sufficient in the diet but due to lack of information or due to poor eating habits

anemia is still very prevalent. 60% of female population has hemoglobin of 10grms or even less.

Hemoglobin of more that 11grms is very uncommon. This makes them vulnerable to

complications. Even very small blood loss during delivery may cause symptoms of hemorrhage

in these cases. It is necessary to repeatedly check hemoglobin levels and attend to the nutrition

supplements.

This cause of maternal mortality and morbidity can be easily prevented by proper nutrition and

supplementation. It is not possible to procure all anti-anemic factors in the diet. In view of this

supplementation is the best way to fight this scourge which leads to poor vitality.

Our aim is to have every woman with hemoglobin of at least 12gms. This will help in reducing

mortality and morbidity of the mothers and open the doors to happiness in the family. She can

then have energy to look after her family and also to produce enough milk for her new born baby.

Let us make the Indian women enjoy her role to the full.

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Ideal Body Weight and Recommended Caloric Intake During Pregnancy

Height Ideal Body Weight (Kilograms)

Recommended Caloric Intake During Pregnancy ( 35 Kcal / Kg )

17014'10” 48.6

17504'11” 50.0

17995'0” 51.4

18455'1” 52.7

18945'2” 54.1

19575'3” 55.9

20375'4” 58.2

21005'5” 60.0

21635'6” 61.8

22265'7” 63.6

23005'8” 65.7

23005'8” 65.7

23565'9” 67.3

24195'10” 69.1

Nutrient Normal RDARDA during pregnancy

Risks of deficiency in mother and fetus Sources

Zinc 12 mg/ day 15 mg/ day

Intrauterine growth retardation, malformations, premature and postmature birth, LBW, perinatal death and abnormal delivery with dystocia and placental abruption

Red meat, sea food, yogurt, bread, lentils, milk, peas, baked potatoes.

Iron 15 mg/ day 30 mg/ dayMaternal anemia, fetal anemia, LBW and preterm delivery

Apple, jaggery, dry fruits

Copper 1.5 - 3 mg/ dayPlacental insufficiency andintrauterine death

Cooking in copper vessel1.5 - 3 mg/ day

Chromium 50 - 200 :g/ dayGestational diabetes and hyperglycemia

Onions, tomatoes, broccoli, white meat, grape juice, red meat, green beans.

50 - 200 :g/ day

Selenium 55 :g/ day

Neural tube defects, sudden infant death syndrome and first- trimester miscarriages

Asparagus, mushroom,garlic, red meat, sea food.

65 :g/ day

Iodine 150 :g/ day

Miscarriage, stillbirths, congenital anomalies., goiter, cretinism, impaired brain function and hypothyroidism

Iodized salt, sea food175 :g/ day

Folic acid Neural tube defects in fetus

Meat, liver ( best source), chicken kidney, egg yolk, almonds, lentils, beetroot, banana, whole wheat grain

15 :g/ day

Nutrient Requirements In Women

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Mirror, mirror on the wall….

which is the best iron of them all?

Dr. Susheela Rani B. S.

Manjushree Speciality Hospital Bangalore

Iron deficiency is the most common nutritional disorder in the world. The World Health

Organization ranked it as the seventh most important preventable risk for disease, disability, and

death in 2002. In a developing country like ours the woman is always in a state of precarious iron

balance during the reproductive years. She is born anemic, grows anemic, and enters the

pregnancy in an iron deficient state and becomes even more anemic with successive pregnancies.

The iron stores are not well developed because of poor nutritional intake, recurrent infections,

menstrual blood loss and repeated pregnancies. Gender discrimination in our country ensures

that the girl child lacks access to balanced diet, adequate health care and proper education. Thus

the average Indian woman is almost always in an iron deficient state.

The most common strategies employed to control the iron deficient state are:

1. Food fortification

2. Iron supplementation

Supplementation of Iron in pregnancy – 60mg /day

Treatment of Iron deficiency – 120 - 180mg /day

Iron Toxicity

Iron poisoning is rare in adults, but serious acute toxicity may occur in children. The estimated

lethal dose of iron is 200 to 300 mg/kg. The majority of cases are non-fatal and without serious

morbidity. Fatalities are generally attributable to accidental ingestion of adult, rather than

paediatric, iron supplements. Many iron preparations are therefore aimed at making them safe by

increasing the lethal dose.

Iron fortification of food

Food-iron fortification (at levels to provide around 5–15 mg/day, in foods such as wheat flour,

salt, sugar, rice, fish sauces and pastes) is common in developing countries, where iron

The Recommended Dietary Allowance (RDA) for females

Category

Adolescent girls 18 mg

Mixed Diet Veg Diet

26 mg

Premenopausal 25 mg 33 mg

Postmenopausal 8 mg 14 mg

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deficiency is widespread and food fortification is relatively inexpensive in comparison to

pharmacological supplementation.

In the UK there is mandatory iron fortification of white and brown flour.

Many breakfast cereals, malted drinks, some biscuits and snack foods are

fortified on a voluntary basis. Ferrous sulfate is the most commonly used

fortificant for cow milk or infant formulas. Rice fortified with a standard

ferrous sulfate mix has been used successfully in the Philippines. Curry

powder has been successfully fortified with iron- EDTA in South Africa.

The technology for fortifying common salt with iron has been developed

indigenously in India.

A double-blind controlled iron fortification trial using NaFeEDTA in masala powder (10 mg/g

masala) was directed towards an iron deficient Indian population. The iron status of the fortified

groups improved more than that of control subjects, the prevalence of iron deficiency anaemia

decreased from 22 to 5% in fortified females. It is reported that fortified subjects with normal iron

status did not accumulate excessive body iron and no adverse effects were observed.

Another double blind randomized controlled study was conducted among school children in

Bangalore, India. The study showed that when school children were fed with extruded rice

fortified with micronized ground ferric pyrophosphate in their midday meal for 7 months, iron

deficiency anemia was reduced by 50%.

Thus it has been proven beyond doubt that iron fortification of food can make a positive

difference to the health statistics of our country.

Pharmacological iron supplementation

A wide range of iron containing products (more than 70) is available in pharmacies. These include

products that contain only iron salts, iron combined with zinc and/or folic acid and numerous

multinutrient products. The indication for products that only contain iron is the treatment or

prevention of iron deficiency. The multinutrient products have a range of indications including

use when intake or absorption of nutrients may be suboptimal such as postoperatively, in severe

chronic disease, in malabsorption syndrome, in pregnancy and where diet is restricted.

A factory where wheat flour is

fortified with iron

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Side effects of Iron supplementation

Therapeutic doses of iron supplements, which are prescribed for iron deficiency anemia, may

cause gastrointestinal side effects such as nausea, vomiting, constipation, diarrhea, dark colored

stools, and/or abdominal distress.

Enteric coating & delayed release

Modified release [MR] preparations, some in 'Spansule' formulation, are designed to release iron

gradually as the preparation traverses the GI tract so that at any given time, only a small amount

of iron is present in the lumen. The advantages

claimed are less GI irritation and a long duration of action permitting once or twice daily dosage.

However, these preparations are likely to carry the iron beyond the first part of the duodenum

where the conditions for iron absorption are optimal and the lower incidence of intolerance may

well be due to the fact that a smaller quantity of iron is actually released and absorbed.

Furthermore, technical failure of the preparation can lead to dose-dumping and even to entire

tablets being passed out in stool.

Iron absorption enhancers

A variety of substances designed to enhance the absorption of iron has been marketed, including

surface acting agents, carbohydrates, inorganic salts, aminoacids and vitamins. One of the more

popular of these is ascorbic acid. When present in an amount of 200mg or more, ascorbic acid

increases the absorption of medicinal iron by at least 30%. However the increased uptake is

associated with a significant increase in the incidence of side effects; therefore addition of ascorbic

acid seems to have little advantage over increasing the amount of iron administered. It is

inadvisable to use preparations that contain other compounds with therapeutic actions of their

own, such as Vit B12, folate, cobalt etc, since the patient's response to the combination cannot be

easily interpreted.

Tips to enhance iron absorption

1. Starting with half the recommended dose and gradually increasing to the full dose will help

minimize the side effects.

2. Taking the supplement with food also may help limit gastric symptoms at the cost of reduced

absorption.

3. Inclusion in the meal fresh fruits or fruit juices and other sources of vitamin C such as

tomatoes, spinach, cabbage, cauliflower, potatoes and other green leafy vegetables.

4. Consume milk, cheese and other dairy products as between-meal snacks rather than at

mealtimes

5. Separate tea drinking from mealtime by at least 2 hours

A number of iron preparations are currently available in the Indian market for the prevention and

treatment of iron deficiency anemia. Each preparation claims some benefit over the others leaving

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the physician in considerable confusion. How does one choose the best

iron supplement? Apart from being bio available, clinically effective

and having minimal side effects, an ideal iron supplement needs to be

safe and cost effective. While the effectiveness of most iron

preparations available in the market remain the same, the benefits

claimed are in reducing the side effects, making them tolerable and

increasing their safety.

Oral Iron Supplements

1. Ferrous salts

All dietary iron has to be reduced to ferrous form to enter the mucosal cells. Hence bivalent iron

salts like ferrous sulfate, fumarate, gluconate, succinate, glutamate and lactate have been

preferred over ferric salt preparations. In addition these salts are amongst the cheapest

preparations of iron available for medicinal use.

Bioavailability

These salts have uniformly good bioavailability. However, the bioavailability decreases

markedly in the presence of dietary inhibitors like phytates, tannic acid etc. They cannot be added

to other foods/milk/fortified formulas for the same reason.

Clinical efficacy

Despite being efficacious and cheap with good bioavailability, ferrous salts have several

disadvantages particularly the high incidence of gastrointestinal side effects (~23 %). Teeth are

known to be stained with liquid preparations. Ferrous sulphate has a salty astringent taste.

Safety issues

Any over dosage of the salt can easily override the 'mucosal barrier' to cause acute iron toxicity.

The LD50 for ferrous sulphate is 320mg/Kg body weight.

Salt of Iron

Ferrous sulphate

Trade name - Pharma

Ferrous fumarate

Iberol - Upjohn

Ferrous gluconate JP Tone - Jagsonpal

Ferrous lactate

Irex 12 - MicroAutrin - WyethSofteron - AristoRediplex - PfizerLivogen Z - Merck

Ferrous succinate Hematrine Novartis Pharma

Ferrous ascorbate Ferium XT - EmcureOrofer XT - Emcure

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2. Ferric salts

Ferric salts have traditionally not been preferred over ferrous salts as the ferric ion first requires

reduction to ferrous form in the intestinal lumen and usually this reducing capacity is not enough

to reduce doses of iron therapeutically administered.

Bioavailablility

The bio-availability of iron from ferric salts is 3 to 4 times less than that of ferrous sulphate.

Therefore, the dose of ferric salts needs to be 4 times more than ferrous salts to achieve similar

therapeutic effect.

Safety

Ferric salts carry the inherent advantage of a poor poisoning potential given the limited reducing

ability of the gastric contents. Ferric ammonium citrate (18% elemental iron) is the most

commonly used of these salts.

3. Iron Amino-acid chelates

Iron amino-acid chelates are conjugates of the ferrous or ferric iron with amino-acids. Although

numerous conjugates have been formulated the most studied of these are ferrous bis-glycinate

(20% elemental iron content), ferric trisglycinate and ferrous glycine sulphate. They have no

effect on the color or taste of food products.

Bioavailability

Their main advantage lies in their relatively high bioavailability in the presence of dietary

inhibitors. It is theorized that the chelates prevent iron from binding to inhibitors in food or

precipitating as insoluble ferric hydroxide in the pH of the small intestine. Studies have shown

that iron absorption from ferrous bisglycinate is better than ferous sulphate in the presence of

dietary phytates.

Safety

These conjugates have low pro-oxidant properties thereby limiting free radical damage and are

environmentally stable.

Trade name

Ferrous bisglycinate Ferose - CFL

Pharma

Fe Glycine sulphate Hemfer - Am. Rem

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4. Iron (III) Polymaltose Complex (IPC)

IPC is a novel iron preparation, which contains non-ionic iron and polymaltose in a stable

complex.

Bioavailability

IPC and FS have been demonstrated to have equivalent bioavailability. Absorption of IPC is not

affected by food or milk, enabling administration without consideration of the timing of feed.

Also, to date there are no reports of any interactions with foods or medicines.

Clinical efficacy

The usefulness of IPC in the treatment of IDA has recently been a topic of much debate. Contrary

to earlier reports, there are several other reports of inadequate or slower rise in hemoglobin.

Safety

Iron of IPC is absorbed in the intestine through a self-limiting competitive interchange of ligands,

so that the intestinal transport system is saturated in case of over dosage. Accidental intoxication

with IPC is therefore rarely seen.

5. Carbonyl Iron

Carbonyl iron is a small particle preparation of highly purified (98%) metallic iron. 'Carbonyl'

describes the process of manufacture of the iron particles (from iron pentacarbonyl gas). The

particle size is less than 5 microns as compared to Ferrous fumarate which is 30-100microns. The

stomach acid solubilizes this iron. In the process of this solubilization H+ ions are consumed

thereby increasing the gastric pH. Also, as a result the absorption of iron is slow (permitting

continued release for 1 to 2 days) and self limited by the rate of acid secretion by the stomach

mucosa.

Bioavailability

After oral administration of equivalent amounts of carbonyl and ferrous iron, the amount of iron

absorbed, and the internal distribution of absorbed iron are all similar. As a food fortificant its

advantages include lack of change in color or taste of the foodstuff and environmental stability.

Clinical efficacy

Carbonyl iron is as effective as Ferrous sulphate in bringing about mean Hb increase. Estimates of

net changes in total body iron suggested that the overall bioavailability of carbonyl iron was high,

about 70% that of ferrous sulfate. Subsequent studies have shown that Carbonyl iron was as

effective and safe in prevention and treatment of iron deficiency with lesser side effects compared

to FS.

Trade name

Mumfer Z Glenmark

Pharma

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Safety

Carbonyl iron is much less toxic than ionized forms of iron. Whereas the lethal dose of FS is 320

mg/kg. Toxicity studies of carbonyl iron in animals demonstrated a lethal dose of 50,000 to 60,000

mg/kg

6. Iron EDTA

Ethylene diamine tetraacetic acid (EDTA) is a hexadentate chelator, which can combine with

virtually every metal in the periodic table. Binding of EDTA with iron is favoured in the acid

milieu of the stomach, irrespective of whether the EDTA is administered as CaNa2EDTA,

Na2EDTA, or NaFeEDTA, but in the more alkaline medium of the duodenum the iron is

exchanged, in part, with other metals. The iron released from EDTA is absorbed by the normal

physiological mechanisms. When NaFeEDTA is present in a meal, the iron moiety exchanges

with the intrinsic food iron and the EDTA partially protects the iron in this common non-heme

iron pool from the effects of inhibitors of iron absorption, such as phytates and polyphenols.

Efficacy

When iron is added as NaFeEDTA to an inhibitory meal, it is two to three times better absorbed

than is iron added as ferrous sulfate.

Safety

There is no evidence that NaFeEDTA in the dose range proposed for food fortificants (5 to 10 mg

iron daily) will have any direct toxic effects. Na2EDTA and CaNa2EDTA have proved safe over a

number of years, while the Joint FAO/WHO Expert Committee on Food Additives concluded in

1999 that NaFeEDTA "could be considered safe when used in supervised fortification programs"

NaFeEDTA seems to be an appropriate fortificant for developing countries; its cost is about six to

eight times that of ferrous sulfate in terms of equivalent amounts of iron. Its better absorption (a

factor of 2-3) might make it possible to halve the daily fortification level but, it still remains

expensive and there is a pressing need for food grade NaFeEDTA at more affordable prices.

Trade name

Fefol Z GSK

Pharma

Carboflot Glenmark

Richar Dabur

Ferox Micronova

Café Kit Aristo

Trade name

Redfine Dr. Reddy's Lab

Pharma

Nobefer plus Ochoa

Haemgrow Fem Care

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7. Other iron formulations

Several other iron preparations are in various stages of development or being gradually phased

out. Heme based preparations. Hemoglobin as a source of iron was promoted on the basis of the

high bioavailability of heme iron. However the iron content of hemoglobin is 0.34 %. As a result

300 mg of hemoglobin is required to deliver 1 mg of elemental iron which leads to large volumes

and prohibitory costs.

Newer preparations

Ones under study include ferrous oxalate, microencapsulated ferrous sulphate and

microencapsulated ferrous fumarate. Ferrous oxalate has been recently found to have good

efficacy and low toxicity in studies conducted on piglets.

Sprinkles

Recently, a supplement containing microencapsulated

ferrous fumarate (plus ascorbic acid) has been developed

which can be sprinkled on any complementary food at the

table given by the caregiver. Sprinkles are sachets (like small

packets of sugar) containing a blend of micronutrients in

powder form, which are easily sprinkled onto foods

prepared in the home. Any homemade food can be instantly

fortified by adding Sprinkles. Iron being encapsulated does

not change the taste, colour or texture of the food to which Sprinkles are added.

Similarly, a ferrous sulphate preparation microencapsulated with phospholipids was found to

have equivalent bioavailability to FeSO4. These may have important implications for community

intervention programmes in which initial high-dose treatment is needed because of a high

prevalence of anaemia.

Conclusion

v In a country like India, where iron deficiency is rampant, fortification of food with iron

when introduced on a large scale will make a great impact in the health of our women.

v Ferrous sulfate remains the standard first-line treatment of iron-deficiency anemia given its

general tolerability, effectiveness, and low-cost but with the possible risk of iron toxicity.

v Carbonyl iron, iron chelates, NaFeEDTA are as good as Ferrous sulphate in terms of

haemoglobin rise but are more biovailable and / or better tolerated. All these preparations

are much safer than Ferrous sulphate in terms of toxicity.

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Bibilography

Joydev Mukherjee Iron deficiency anemia in pregnancy, Rational Drug Bulletin, Vol12, No1, Jan-

Mar 2002

Stoltzfus R., Dreyfus M.L.. Guidelines for the use of iron supplements to prevent and treat iron

deficiency anemia.

Edited by INACG, WHO and UNICEF. IUNACG. Washington.1998

Food Fortification Approaches, IH552 Elimination of Micronutrient Malnutrition

Expert group on Vitamins and Minerals EVM/00/12.REVISEDAUG2002

Rebecca J. Stoltzfus, Michele L. Dreyfuss Guidelines for the Use of Iron Supplements to Prevent

and Treat IDA, Int Nutritional Anemia Consultative Group

Peter Jacobs, Lucille wood, Better tolerance of IPC compared with Ferrous sulphate in the

treatment of Anaemia, Hematology 2000, Vol: 5, p77-83

Morgan EH, Oates PS. Mechanisms and regulation of intestinal iron absorption Blood Cells Mol

Dis. 2002 Nov-Dec;29(3):384-99

Devasthali SD, Gordeuk VR, Bioavailability of carbonyl iron: a randomized, double-blind study.

2: Eur J Haematol. 1991 May;46(5):272-8.

Gordeuk VR, Brittenham GM, High-dose carbonyl iron for iron deficiency anemia: a randomized

double-blind trial. Am J Clin Nutr. 1987 Dec;46(6):1029-34.

Anna EO Fisher, Declan P Naughton Iron supplements: the quick fix with long-term

consequences Nutriton Journal, Jan 2004, Vol 32, p 1-5

Christofides A, Asante KP, Multi-micronutrient Sprinkles including a low dose of iron provided

as microencapsulated ferrous fumarate improves haematologic indices in anaemic childre.

Matern Child Nutr. 2006 Jul;2(3):169-80

Zimmermann MB, Muthayya S, Moretti D, et al. Iron fortification reduces blood lead levels in

children in Bangalore, India. Pediatrics. 2006 Jun;117(6):2014-21.

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REFRACTORY ANEMIAS IN PREGNANCY

Dr. Biliangady Reeta H. DNB, DGO

Director: 'NORTH STAR' Hospital for Women

Bangalore

Definition: Refractory anemia is anemia which does not respond to therapy or shows incomplete

response to adequate doses of hematinics.

CASE - DISCUSSION

Mrs. G aged 22 years seen at fifteen weeks gestation with Hb of 7.3g% PCV of 23% is started on

seen at 15 weeks gestation is started on iron supplement containing 60mg of elemental iron in a

dose of two tablets per day four weeks later a repeat Hb test shows Hb to be 7.5g% and a PVC of

24%. A peripheral smear at this time is reported as one of Microcytic Hypochromic type. The iron

preparation is changed from one of ferrous gluconate to ferrous fumarate and Hb is repeated after

four more weeks. The report is given as 8.0g%. This is a common situation encountered in clinical

practice.

Normal expected response to iron therapy: Hematological response to iron therapy in the form of

increased Hb varies with the degree of anemia. When anemia is exclusively due to iron deficiency

Hb takes usually two months to reach normal values. However when there is no cause for anemia

other than iron deficiency the Hb should increase to a point half way between the starting level 1

and the normal in about eighteen days . If this does not happen one should find out the cause for

refractoriness to therapy.

Causes of refractoriness to therapy:

i. Wrong diagnosis

ii. Non Compliance.

iii. Persistent cause for anemia.

Wrong Diagnosis: Failure of response to treatment is often due to wrong clinical diagnosis of the

cause of anemia or wrong diagnosis of the type of anemia.

The commonest type of anemia encountered in pregnancy is iron deficiency anemia..

Megaloblastic anemia however is seen in only 3 – 4% of women with anemia during pregnancy

and in the vast majority it is due to Folic acid deficiency Vitamin B deficiency begins often in the 12

third trimester or after delivery and is mainly due to dietary deficiency which commoner

amongst vegetarians. Clinical manifestations develop when the tissue stores are completely

exhausted. Addisonian Pernicious anemia is rare in the reproductive years. Also severe

Vitamin B deficiency is associated with infertility. Chronic tropical sprue is another rare cause 12

of Vitamin B deficiency in pregnancy when anemia is refractory to iron therapy Folate and 12

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Vitamin B deficiency is to be suspected and investigations must be directed accordingly. The 12

essential feature of iron deficiency anemia is diminished concentration of hemoglobin in

microcytic red cells where as the red cell number need not be reduced. The Mean Corpuscular

Volume (MCV) and Mean Corpuscular Hemoglobin (MCH) are reduced.

The first indication of megaloblastic anemia, irrespective of whether it is Folate or Vitamin B12

deficiency in pregnancy is an elevated MCV. A reticulocyte count count however might help to

differentiate Folate from B deficeincy the count is normal in Vitamin B and elevated in Folate 12 12

deficiencies. Also in case of iron deficiency anemia which is not accompanied by folate deficiency

hypesegmentation of polymorphonuclear leucocytes is the characteristic feature. This is absent in

associated folate deficiency. Hence diagnosis of folate deficiency in pregnancy is on morphologic

grounds and is best done by examining a smear of bone marrow aspirate. (For details refer to

chapter 'Investigations; What, When & Why')

Management of Folate Deficiency in Pregnancy: WHO recommends a daily dose of 400µg of

Folate during pregnancy and postpartum. Since the diet of majority of pregnant women does not

provide this requirement it is recommended to supplement pregnant women with 0.4mg per day 2

of Folic acid Once megaloblastic erythropoiesis is established it is an indication that there is

megaloblastic change in the gastrointestinal tract also. This is associated with malabsorption and

treatment becomes difficult. However as a first line of treatment oral folic acid in a dose of 5.0mg

per day is recommended. In case of persisting anemia parenteral folic acid may have to be tried. 3

The recommended dose is 1 mg per day for one week .

The recommended intake of Vitamin B is 3µg per day during pregnancy which is available in the 12

diet of a non - vegetarian. However a strict vegetarian needs to be supplemented. In case of

established Vitamin B deficiency parenteral Cyanocobalamin should be administered in a dose 12

of 250µg per month. In women close to delivery cyanocobalamin in the dose of 100µg per day for a 3

week may be necessary .

Hemoglobinopathies: Hypochromic anemia in pregnancy is mainly due to iron deficiency.

However if the anemia does not improve in spite of adequate iron and folate supplements it is

necessary to rule out the less common situations where the red cell morphology is abnormal not

due to lack of iron but is due to lack of iron utilization or due to abnormal globin synthesis in the

red cell precursor. Hemolytic anemias which could be either acquired immune hemolytic type or

hemolytic anemias associated with hemoglobinopathies e.g. sickle cell trait, beta thalassemia

minor and sickle cell disease (For details refer to relevant chapters).

Noncompliance as a cause of refractory anemia: It is common among pregnant women in our

country to either take iron irregularly or discontinue therapy often because of gastrointestinal

side effects. A detailed questioning is necessary. Often one may have to obtain the details from the

spouse or a caretaker at home. Iron intolerance in the form of nausea, vomiting, abdominal

discomfort, colicky pain, diarrhea or constipation with conventional therapeutic dose is common

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in pregnancy. Symptoms are often dose related. These can be avoided by starting smaller doses of

iron which can be increased gradually and also by administering iron with meals or immediately

afterwards. A sustained release preparation of iron can be tried if symptoms persist. In case this

too fails parenteral iron therapy is required (For details refer to chapter on 'Mirror Mirror on the

wall which is the best Iron of them all').

Persisting Cause for Anemia: If there is a persistent hemorrhage, occult or obvious it can lead to a

partial or complete failure of response to iron therapy. An occult cause is often in the

gastrointestinal tract which requires evaluation in the form of stool examination and GI

endoscopy. An obvious cause of hemorrhage like hemorrhoids or fissure in ano should be treated

appropriately. Hookworm infestation still remains a major cause of persisting anemia, especially

in the rural pregnant women and women of lower socioeconomic strata.

Less common causes of failure of response to iron are

a. Disorders affecting bone marrow function like

i. Chronic Infections e.g. malaria, urinary tract infection, tuberculosis.

ii. Worm infestations

iii. Chronic Renal Insufficiency.

iv. Co existing B and Folate deficiency 12

b. Malabsoption of Iron as in

i. Alimentary tract disease e.g. chronic diarrhea, irritable bowel syndrome.

ii. Occult Malabsorptive Disease.

c. Protein Calorie Malnutrition

d. Improper administration of iron e.g. administration of Calcium and Iron together impairs

iron absorption.

e. Undiagnosed hypothyroidism.

f. Bleeding hemorrhoids and fissure.

In these situations the underlying cause for lack of response should be treated and in case of

malabsorption parenteral iron therapy is to be considered.

References

1. G. Richard Lee. Iron deficeincy and Iron deficiency anemia In. Wintrobe's Clinical

Hematology. 10th Ed. Williams & Wilkins; 1998; 979 – 1010.

2. Stoltzfus R.J. et al guide lines for the use of Iron Supplements to prevent and treat Iron

deficiency anemia on behalf of the International Nutritional Anemia consultative group

(INACG) Washington, 1998, International life sciences Institute press.

3. Bitran J. D et al Megaloblastic anemia during pregnancy J Rprod Med 1977; 19; 186 – 192

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Hemotherapy In ObG :

When, why And How?

Dr. Shivaram C,

Chief, Transfusion services,

Manipal Hospital, Bangalore.

One of the earliest documents on Blood transfusion by Andreas Libavius(1546-1616) reads as

follows:

“Let there be a young man , robust, full of spirituous blood, and also an old man thin, emaciated

and exhausted. Let the performer of the operation have 2 silver tubes fitting into each other. Let

him enter the artery of the young man, and put in one of the tubes. Let him open the artery of the

old man and put the female tube into it and then the two tubes being joined together the blood of

the young man will pour into the old one as it were from a fountain of life, and all his weakness

will be dispelled.”

The first recorded man-man transfusion transfusion was carried out by James Blundell, an

English obstetrician who saved the life of a lady who was having severe post partum hemorrhage

by transfusing the husband's blood at a time(1818) when even blood groups were yet to be

discovered by Karl Landsteiner(1900).

However, today we can no longer rely only on spirituality for safe blood, nor is husband's blood

considered appropriate for the wife to avoid sensitization with paternal antigens. However,

husband's can receive wife's blood since they don't give birth to babies!

Blood safety has three elements.

1>Safe donor (Altruistic Voluntary blood donor)

2>Safe blood ( Good testing methodology-ELISA/NAT )

3>Safe Transfusion by clinicians-the end users of blood.

Why do women need blood ?

According to a nationwide Indian study carried out by Tim Bray etal

Adult recipients account for 87% of transfusions, and amongst the age group of 25–34, 73% of

transfusions were for women. Anaemia was listed as a reason for 60% of transfusions, surgery for

42%, acute haemorrhage for 26% and pregnancy for 16%. Seventy-four per cent of adult

transfusions were inappropriate.

According to another study in Bangalore (due for publication) 3 out of 4 deaths that took place in

Bangalore as a consequence of Post Transfusion GVHD in 2005-2006 were caused by

encouragement / acceptance of relatives' blood by Obstetrician / gynaecologists.

Anemia among Indian women is a very common entity. According to a survey 52 % women have

anemia and 17 % have moderate to severe anemia. MMR in India continues to be high. While the

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IMR has declined significantly over the years a proportionate drop in MMR is yet to be seen.

Anemia is responsible for 14-24% of the maternal deaths, while bleeding during pregnancy is

responsible for 16-26% of maternal deaths. Access to good quality blood / blood components

coupled with its rational use can significantly contribute to reducing MMR in India.

Comparison with rest of the world:

The need for transfusion of red blood cells (RBC) during pregnancy and the peripartum period is

fairly significant occurrence seen in 1% to 2% of all pregnancies in the developed countries. It has

been estimated that RBC transfusions are given in 0.3% to 1.7% of vaginal deliveries, between

0.7% and 6.8% of cesarean deliveries, and in as much as 8.6% of cases of ruptured ectopic

pregnancies.(Obstetrics & Gynecology 2004;104:1000-1004 ) Although no Indian data is

forthcoming on this, blood usage especially whole blood usage in pregnancy / peripartum

period is very common in India. Use of whole blood to reach that magical figure of 10 g% is

probably unnecessary in majority of cases.

As a general rule, only RBC transfusions should be given that too, only when absolutely

necessary. This will minimize the risks of exposure to allogeneic blood products and risk of

exposure to infections. Use of whole blood in pregnancy to correct anemia overburdens the

already burdened heart. Use of whole blood for massive blood loss corrects anemia but leads to

dilution of platelets and coagulation factors leading to complications of massive transfusion like

coagulopathy, acute DIC.

FRESH WHOLE BLOOD:

Use of fresh blood to correct platelet deficiency and clotting factor deficiency (result of massive

transfusion with whole blood) is not practically possible due to the volumes involved. Further,

use of fresh blood necessitates screening by the less accurate Rapid/spot tests as opposed to the

more accurate ELISA tests. Further, infectious agents like T.Pallidum can survive in fresh blood.

Fresh blood upto 3 days old is more likely to have viable white cells and has been to shown to have

greater chances of inducing Graft Versus Host Disease-a life threatening complication of blood

transfusion. Fresh whole blood is a vestige of past transfusion practices when appropriate

components were not available. American association of Blood banks has no indication for

whole blood transfusion in modern medical practice.

Causes of anemia

1> Increased red cell loss

v Acute: trauma / surgical / obstetric haemorrhage

v Chronic blood loss: GIT / urinary tract / reproductive tract / parasitic infestation /

malignancy / inflammatory / hemolytic disorders

2> Decreased production of red cells

v Nutritional deficiency – iron / B12 / folic acid / malnutrition

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v Bone marrow failure

v Renal failure (decreased erythropoietin production)

v Chronic illness

v Lead poisoning

v Increased destruction of red cells

v Infections – bacterial / viral / parasitic

v Hemoglobinopathies

v Drugs-dapsone

v HDN

Acute Anemia

It is the result of acute blood loss – surgical / traumatic

v Acute Blood Loss

v Blood Vol decreased

v Total Hb is decreased

v O2 storage / transport / delivery decreased

Decreased Hb X Decreased O2 saturation X Decreased Cardiac output = Diminished O2

supply to tissues in acute anemia.

v Compensatory mechanism activated:

v Restoration of plasma Volume

v Restoration of Cardiac out put.

v Stimulation of ventilation

Chronic anemia

v Continued blood loss - small quantities.

v Nutritional deficiency

v Hemoglobinopathies

v Increased demand for red cells

v Pregnancy / Lactation

COMPENSATION

v Cardiac output increased

v O2 dissociation curve of Hb shifts to increase O2 release

v Fluid retention

Decreased Hb X Increased Saturation X Increased Cardiac Output =Maintains O2 supply to

tissues.

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Management of Acute Anemia

v Treat underlying cause(Iron/B12 etc)

v Assess degree of oxygenation

v Improve O2 supply if needed.

v Transfuse ONLY RED CELLS, not whole blood, when O2 supply is inadequate.

v Transfusion in megaloblastic anemia: Dangerous because of the co-existent poor

myocardial function which could precipitate heart failure.

v Immune anemias: Antibodies in patient's serum may hemolyse not only transfused red

cells but patient's own remaining red cells.

Management of Chronic Anemia

v Exclude hemoglobinopathy

v Identify & correct blood loss: Local bleeding / helminthic infestation.

v Oral iron / B12 / folic acid

v Consider and treat malaria

v Review drug history – NSAIDS / Dapsone / anticoagulants / marrow suppressive

drugs

Treatment of Severe decompensated Anemia

v Treat infections

v Give O2 by mask

v Correct fluid balance

v Transfuse red cells in the right dose along with a diuretic like frusemide.

v It is not necessary to restore the normal Hb.

v Raise it just enough to relieve the clinical symptoms (usually 8g/dL is sufficient).

RED CELLS: When to Transfuse

ACUTE BLOOD LOSS

The primary treatment of acute blood loss is not blood. It is crystalloids / colloids.

Upto 20% Blood loss

v Give Crystalloids - Normal Saline / Ringer Lactate.

v Volume needed for replacement is 2-3 times the volume lost.

v Anticipate risk of fluid overload.

Continued loss

v Add colloids - 5% Albumin or hydroxyethyl starch.

v Replace colloids volume for volume

v 30 % Blood loss:

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v Use red cell concentrate (packed red cells) to correct volume & oxygenation.

v If there is uncontrolled bleeding and laboratory evidence of coagulopathy – add fresh

frozen plasma.

v If bleeding continues - consider platelets after investigations.

v Use appropriate blood group switches when same group is not available.

THRESHOLD FOR RED CELL TRANSFUSION:

Historical Facts

v MAYO CLINIC in 1900 proposed a target value of 8-10 g/dL.

v CURRENT PRACTICE (NIH Consensus) is 7g/dL in the absence of disease 8-10g/dL in

the presence of disease (cardiovascular disease / risk factors / elderly).

Rate of fall of Hb is more important than the actual Hb value

Healthy individuals tolerate Hb levels as low as 5g / dL

RELATIVE EFFICACY

Whole Blood Red cells

v Volume 350 ml 250 ( 350ml with Additive solution)

v Haematocrit 40% 75%

v Red cell volume 160ml 190 ml

v Increase in Hb% 1g/dl 1. 3g/dl

v Unwanted plasma Plenty Minimal

v Platelets None None

v Complications More likely Less likely

v Cost More Less

LEUKO-DEPLETED RED CELLS : Why to use ?

v Avoids treatment of multiple febrile transfusion reactions.

v Prevention of CMV transmission

v Prevention of allo-immunisation to leukocytes and platelets

LEUKO-DEPLETED RED CELLS: When to use ?

v Multiply transfused patients.

v Multiparous women

v Intrauterine transfusions

v Exchange transfusions in newborn

v Haemoglobinopathies-Thalassemia

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v Bone Marrow Transplantation

v Leukemias,Solid tumours, other immunodeficiency states

MASSIVE TRANSFUSION

v Replacement of patient's blood volume in 24 hrs.

v Transfusion of >20 units of red cells in 24 hrs.

v Replacement of >50% of patient's blood volume in 3 hrs.

v Replacement for blood loss >150ml/min in an adult.

POTENTIAL COMPLICATIONS:

v Thrombocytopenia

v Coagulopathy

v DIC

v Hypocalcemia

v Hyperkalemia

v Metabolic acidosis

v Hypothermia

THERAPY: Correct thrombocytopenia with platelets and coagulopathy with FFP.

Cryoprecipitate may be used to replace fibrinigen or factor VIII. Warming of blood is indicated

only in case of massive red cell transfusions.

Modifications of routine practice can minimise the need to transfuse red cells,

v Checking for and correcting anaemia before planned surgery.

v Stopping anti-coagulants and antiplatelet drugs before planned surgery

v Minimising the amount of blood taken for laboratory samples.

Current Transfusion Trigger for Red cells

v Local guidelines are important; local factors must be taken into account.

v Large randomised clinical trial ( Level I evidence) in critically ill patients demonstrated that a

restrictive transfusion policy : aimed at 70-90 g/l is at least equivalent, and possibly superior,

to a liberal policy maintaining Hb at 100-120g/l.

v In patients without cardiovascular disease, esp. younger patients, maintain haemoglobin

levels in the range 70-90 g/l.

v In patients known to have or likely to have cardiovascular disease, (hypertension / diabetes

/ elderly), maintain haemoglobin in the range 90-100g/l.

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GENERAL GUIDE: In normal healthy individuals, a transfusion threshold of 70g/l is

appropriate. (critical level of 40-50g/l)

Transfusion In Obstetric Hemorrhage

v Monitor CVP and arterial pressure.

v Take samples for transfusion and coagulation screen. Order at least 6 units of red cells.

v Do not insist on cross matched blood if transfusion is urgently needed.

v Warm the resuscitation fluids.

v Transfuse red cells as soon as possible. Until then: - crystalloid, maximum of 2 litres -

colloid, maximum of 1.5 litres

v Restore normovolaemia as priority, monitor red cell replacement with haematocrit or

Hemoglobin. Note that the correct increment can be obtained only 24 hours post transfusion

in case of red cell transfusion and 1 hour post transfusion in case of platelets.

v Use coagulation screens to guide and monitor use of blood components

v If massive bleeding continues, give FFP 1 litre, cryoprecipitate 10 units while awaiting

coagulation results. Cryoprecipitate will need to be repeated twice a day till bleeding is

under complete control.

Appropriate use of Blood components in bleeding patient

FFP: indications and dose for haemorrhage

v More than 1 blood volume replaced or Prothrombin time prolonged with INR >1.5

and/or continued blood loss

Dose: 15 ml/kg or 1 Litre (4 packs) for adult of 60 kg

Platelets: Indications and dose for haemorrhage

v Platelet count below 50 × 109/l (<50,000/ul or cmm), in the presence of bleeding.

v In the absence of bleeding and or fever and if there is no planned invasive procedure a

platelet count of 10,000/ul or cmm is acceptable. Drop in Platelet below this level necessitates

transfusion with platelet concentrates.

v Dose: 4-6 platelet concentrates or one unit of single donor(apheresis) platelets.

Cryoprecipitate: Indications and dose for haemorrhage

v Useful only if the fibrinogen is particularly low(<1g/l) or <100mg/dl.

v Early use of FFP may avoid the need for cryoprecipitate

v Give 10 units initially and repeat based on fibrinogen estimation

v Note: Cryoprecipitate is not available from all blood centres. 5 units of FFP (1000-1250 ml)

contains, typically, the same quantity of fibrinogen as 10 units of cryoprecipitate

(approximately 150-250 ml)

v Dose: one unit/5 kg body weight or 10 units in the adult.

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Intrauterine Transfusion for correction of pre-natal anemia Foetal distress is diagnosed by

diminished middle cerebral artery blood flow detected by ultrasonography. Rising atypical(anti-

D) titres coupled with foetal distress also constitute an ominous sign.

Management :

Transfuse red cell concentrate of group O Negative to achieve the desired target Hb level.

Red cells used for transfusion must have a hematocrit, as high as possible, preferably 90%,

although in practice, blood banks can seldom concentrate red cells beyond a hematocrit of 80%.

Red cells must be sickle cell negative and also negative for CMV infection.

CMV negative blood is difficult to find in our country where majority are exposed to CMV

infection, at some point in their lifetime. An alternative is to use Leukofiltered red cells. Red cells

must be filtered using a “leukodepletion filter for red cells”, which is able to remove more than

99.99% of leukocytes and the CMV within them. Filters are expensive costing about Rs1200/-but

well worth preventing CMV infection in the foetus.

Red cells used for IUT must also be irradiated with Gamma rays (Dose 25 Gy or 2500 rads) to

prevent post transfusion GVHD. Use of buffy coat removed or washed red cells is an inexpensive,

but much less effective alternative to leuko filtration. It is only effective in prevention of febrile

transfusion reactions, not in prevention of CMV infection.

It is desirable to use red cells less than 7 days for prevention of hyperkalemia and acidosis in case

of IUT and neonatal exchange transfusion. This is perhaps the only genuine exception for using

fresh blood in transfusion practice.

Time limits for infusing blood components :

All blood components must be transfused as soon as they are received from the blood bank

without warming them. All blood and blood components must be transfused at the same

temperature at which they are issued without warming. Warming of blood using water baths,

pillows, leaving at room temperature for 30 minutes are all equally erroneous.

Massive transfusion in the adult and exchange transfusion in the newborn are the only exceptions.

Blood is warmed using a blood warmer in these conditions.

Ordinarily one unit of red cells / whole blood must be transfused in 2 hours, never beyond 4

hours. Fresh Frozen Plasma being more fluid, may be transfused over 20-30 minutes after

thawing at 37 C in a sterile water bath. Likewise, cryoprecipitate and Platelet concentrates may be

transfused quickly over 20-30 minutes. It is important to use a new standard blood filter (clot

screen filter) with a pore size of 170 microns for transfusion of red cells / whole blood. The same

filter needs to be used for platelets, FFP and cryoprecipitate as well. Transfusions must be

documented and monitored at start of transfusion, 15 minutes post transfusion and finally at the

completion of transfusion.

More frequent monitoring may be necessary in case of sick patients.

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In emergencies, the following may be used:

v Uncrossmatched group specific blood

v Cells - group “O” of appropriate Rh type

v Plasma – group “AB” (which lacks antibodies)

Conclusion: Anemia and blood loss are very common in women. Transfusion trigger for red cells

in the absence of cardiovascular risk factors (hyperetension / diabetes / elderly) is 7g/dl. In

presence of this, transfuse to maintain a higher level 8-9g/dl.

Platelets need to be given only when the count falls below 10,000/ul in asymptomatic patients.

However, in the presence of bleeding or planned invasive procedure, a count of 50,000/ul is

desirable. Use of FFP in coagulopathy in the absence of bleeding is guided by prothrombin time

and use of cryoprecipitate by fibrinogen levels. Fresh whole blood is not a substitute for blood

components. Avoid fresh blood and relative's blood to prevent GVHD. Transfuse blood without

warming using a filter within a maximum time of 4 hours. Even tested blood is not safe. Rational

use of blood is therefore recommended. Consent for transfusion of blood / refusal of transfusion

along with alternatives offered needs to be documented.

References:

1. Transfusion Medicine ,Volume 13 Issue 1 Page 17 - January 2003 T. J. Bray, P. Salil, H. A.

Weiss, J. D. H. Porter (2003). Transfusion medicine in India: a survey of current practice

2. Policy Barriers Preventing Access to Emergency Obstetric Care In Rural India

Dr Dileep V Mavalankar.,Public Systems Group,Indian Institute of Management, Ahmed)

3. Obstetrics & Gynecology 2004;104:1000-1004

4. Modern Blood Banking and Transfusion Practices, Denis M harmening

5. Transfusion Medicine, Jeffrey McCullough.

6. Technical Manual, AABB

7. BCSH guidelines for transfusion triggers.

8. Shivaram C, Guha's Textbook of Neonatology.

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CONSENT FOR DIRECTED DONATION

1. I have been informed that transfusion between first degree relatives carries with it the risk of

a fatal (life threatening) complication called Post Transfusion -Graft Versus Host Disease.

2. I am also told that although rare (incidence 0.1 % or one in 1000 transfusions) this

complication is more likely to occur with relatives' blood, and is almost always fatal and

treatment for this is almost non-existent.

3. In light of this, I have been counseled by the blood bank staff named below, NOT to use

relatives blood. I have fully understood the risk of GVHD.

4. Further, I have weighed the risks of contracting HIV/ Hepatitis from an unknown donor in

the window phase/incubation period versus Post-Transfusion GVHD from a relative donor.

I understand PT-GVHD is more likely to be fatal than HIV/Hepatitis resulting from blood

transfusion.

5. Despite knowing all this, I still prefer that I / my patient receive blood from our relative only.

This has been explained to me in (language)________________________

I shall not hold the Blood bank/consultants/hospital responsible in the event of my/ my patient's

death due to post transfusion Graft Versus Host disease.

Signature: Sign of Blood bank Staff

Relation to patient Name of staff:

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Anaemia in Pregnancy-A teaching hospital experience

Dr. K . V. MaliniM.D., D.G.O., MICOG, PGDMLE,

Professor, Dept of Obstetrics and Gynaecology,Bangalore Medical College, BANGALORE.

Anaemia is the most neglected and the commonest medical disorder seen in pregnancy. It has a

varied prevalence, etiology and degrees of severity in different populations, being more common

in developing countries. This nutritional problem keeps the woman in high risk category as she is

prone for many complications like PIH, sepsis, prematurity & low birth weight babies( Tyagi et

al1985). Several studies have reported association of anaemia with maternal and foetal morbidity.

This study is undertaken to assess the magnitude of the problem and its impact on maternal and

foetal outcome.

Material and Methods

A retrospective cohort study was conducted in Vani Vilas Hospital attached to Bangalore

Medical College, a premiere teaching institute. It is a 450 bedded referral maternity hospital

catering to the needs of population comprising mainly of low socio-economic group. The study

was undertaken for a period of three months from October – December 2006 and comprised of

retrospective analysis of 1380 singleton pregnant women admitted in labor with anaemia.

Women with multiple pregnancies and antepartum haemorrhage were excluded from the study.

The information regarding age, parity, level of Haemoglobin were collected from the records.

Haemoglobin was estimated by Sahli's method in our institute. Whenever complete haemogram

and stool examination were done, the reports were noted down.

Women were categorized into mild, moderate, severe and very severe group depending on Hb

percentage as per ICMR guidelines, i.e., mild – 10.9 to 10gm, moderate – 10 to 7 gm, severe - < 7gm

and very severe - < 4gm. Various maternal and foetal complication were studied under these four

groups. Standard Normal Variate test (Z Test) and Chi-square test were applied to the

complication observed under these groups.

Observations

The prevalence of anemia among obstetric admissions in our study was 52% (1380 / 2654). Out of

1380 women with anaemia, only 423 were booked and 957(69.4%) were unbooked. Most of the

women belonged to low socio-economic status. The commonest type of amaemia was Iron

deficiency anaemia as evidenced by the peripheral smear.

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Most of the women belonged to moderate group as shown in the graph below.

Anaemia was more common in multi parous women as compared to primis.

Most of them were in the age group of 20 – 29 years

Various complications noted were :

Mild (426)

Moderate (810)

Severe (132)

Very Severe (12)

Distribution of casesn =1380

10% 1%

30%

59%

Parity n = 1380

Primi (588)

Multi (782)

57%

43%

Age distribution

Age in years

< 19 174

Number of cases Percentage

13%

20 - 29 1125 82%

30 and above 81 5%

Complications Mild Moderate SevereVery

SevereTotal

PTD 114 21 135

IUGR 45 12 279222

Birth Asphyxia 3 126 3

MSAF 3 6030 27

IUD 3018 12 1

PIH 129111 126

PPH 31 2

Forceps delivery 241212

CCF 1 1

Sepsis 1 1

Maternal Death 1 21

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Foetal complications like low birth weight (< 2.5kg) babies, preterm deliveries, MSAF, birth

asphyxia, intrauterine deaths and maternal complications like pregnancy induced hypertension

were all seen more in severe and very sever anaemia group as shown in the graphs below.

0%

5%

10%

15%

20%

25%

30%

35%

Mild (80)

Moderate (149)

Severe (46)

Very Severe (4)

Low Birth Weight Babiesn =279

0.00%

5.00%

10.00%

15.00%

20.00%

Mild (31)

Moderate (86)

Severe (16)

Very Severe (2)

PreTerm Deliveriesn = 135

0%

1%

2%

3%

Mild (3)

Moderate (6)

Severe (3)

Very Severe (Nil)

Birth Asphyxian = 12

1%

2%

0%

2%

6%

8%

10%

12%

14%

16%

Mild (5)Moderate (40)Severe (13)Very Severe (2)

MSAFn = 60

18%

4%

0%

2%

6%

8%

10%

12%

14%

16%

Mild (3)Moderate (20)Severe (5)

Very Severe (2)

Intra Uterine Deathn = 30

18%

4%

0%

2%

6%

8%

10%

12%

14%

16%

Mild (25)Moderate (80)Severe (23)Very Severe (1)

PIHn = 129

18%

4%

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There were three cases of atonic PPH, seen in severe and very severe anaemia group. Number of

forceps deliveries were also more in severe anaemia group. There were two maternal deaths, one

as a result of CCF and the second due to sepsis.

Discussion

From our study, it is evident that anaemia is still widely prevalent and is the commonest

preventable medical disorder found in pregnancy. The global prevalence in non-industrialized

countries varies between 35-75%, average being 56% (WHO in 1997). In our study, the prevalence

was 52%. The relative prevalence of moderate and severe anaemia in our study was almost

comparable with ICMR data. But, the number of mild anaemia cases were more in our study and

the number of very severe anaemia cases were more in ICMR study.

Quite a significant number of women were 19 years and below (13%).

Most of the women belonged to low socio-economic status and were unbooked. Nutritional

deficiency was the commonest cause. There were no haemolytic anaemia or

haemoglobinopathies in our study during this study period.

Though severe and very severe anaemia cases formed a small group, most of the maternal and

foetal complications were seen in this group. Since complications were many and each patient

had more than one complication, Standard Normal Variate test (Z Test) and Chi-square test were

applied to all the complications seen in mild and moderate anemia groups and sever and very

severe anaemia groups. It if found that all the complications were higher in the latter group. (Here

p = 0.708)

SE of p = (√pq)/n = (√0.7 x 0.3)/1380 = 0.0123

i.e., Z = (p – P)/((√pq)/n) = (0.708 – 0.5)/0.0123 = 16.26

0%

1%

3%

4%

5%

6%

7%

8%

Mild (6)Moderate (14)Severe (3)Very Severe (1)

Forceps Deliveryn = 24

9%

2%

Groups

Mild 13 %

ICMR Our Study

30 %

Moderate 57 % 59 %

Severe 12 % 10 %

Very Severe 18 % 1 %

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which is much more greater than 3. hence, it can be firmly stated that all the complications were

dependant on severity of anaemia and more in women in severe or very severe anaemia group.

There were total of 10 maternal deaths during study period, out of which two were due to

anaemia. One patient died as a result of CCF secondary to severe anaemia and other died due to

sepsis with very severe anaemia. One of our patients had severe infection of episiotomy wound.

Her Hb% at admission was 4.2gm. She also had term IUD. Surprisingly in our study, there were

no wound infections following LSCS. May be because of blood transfusion before and after

surgery.

ConclusionIn spite of the advances in medicine, and development of modern technologies, nutritional

deficiency anaemia continues to be the major health problem looming large over pregnant

women in developing countries like India.

The fact that most of the women were unbooked proves that either our women are ignorant about

antenatal care or not having access to it.

The incidence of anaemia can be decreased by maternal health education. Importance of

antenatal care should be adequately stressed even if this means campaigning on a door-to-door

basis. 'Catch them Young' i.e., efforts to identify and treat anaemia in the adolescent age group

through school health programmes would be a better idea. Training and motivation of health

workers could go a long way in early detection and treatment of this preventable, social malady at

the grass root level.

Acknowledgement

Dr. Parvathi, Dr. Nirmala, Dr. Saraswathi for assisting in collecting the material.Mr. Joshi – Statistician, Community Medicine Department, BMC Bangalore.

References

v Kishore singh et al-j obst.Gynaec.India.569:45:1995

v Koen MC et al – J obst.Gyanec .India.569:45:1995

v Preety pandya-j.Obst .Gynaec. India.569:45:1993

v Rangnekar AG - J.Obst .Gynaec. India.172.43.1993

v Rathnam.S.S. – Bhaskar Rao, S.Arul kumar -obst gynaec. for P.G.Vol.1 ii edition 1999

v Samir.A.R. International journal -obst .Gynaec. 1995

v Samir Roy – J .Obst .Gynaec. India.743.42.92

v Sharma J B – Nutritional Anaemia during pregnancy in non-industrialized countries,

Progress in Obstetrics and Gynaecology, Studd Vol 15, 2003

v Suresh Deshpande - J .Obst .Gynaec. India. 37:49:1999

v WHO 1997

127

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Blood Banks

Dr. Swetha Arasu Dr. Teena Thomas

Church of South India Hospital

Bangalore

About blood donation:

1. Person above 18 years of age and over 45kgs. in weight can donate blood once in three

months.

2. A normal adult has five to six liters of blood in his/her body of which only 300 ml is used

during blood donation. This blood is replaced by the body within 24 to 48 hours.

3. No special diet, rest or medicine is required after blood donation.

4. The donor should not have taken any medicine in the last 48 hours.

5. The donor should not have contacted jaundice in the previous three years.

6. Every donor is given a medical checkup prior to donation to see if he/she is medically fit and

doesn't suffer from anemia, high blood pressure etc.

7. The donor cannot contract AIDS or any other disease by donating blood.

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For information about negative blood group donors visit http://www.negativegroups.com

BLOOD BANK

M S Ramaiah Medical Hospital

PHONE NO WHOLE BLOOD

PACKED CELLS

FFP PLATELETS CRYOPRECIPITATE

23606545 / 23606524

Rs. 700/- Rs. 650/- Rs. 650/- Rs. 650/- Rs. 650/-

Narayana Hrudyalaya

27835000 / 27835001

Rs. 500/- Rs. 500/- Rs. 500/- Rs. 500/- Rs. 500/-

NIMHANS 26995000 / 26568121

Rs.300/- Rs.300/- Rs.300/- Rs.300/- Rs.300/-

TTK Blood Bank 25293486 / 25287903

Rs.700/- Rs.600/- Rs.600/- Rs.600/- Rs.600/-

Sagar Apollo Hospital 26536700 / 26536701

Rs.940/- Rs.600/- Rs.600/- Rs.600/- Rs.600/-

Victoria Hospital 26701150 Rs.500/- Rs.500/- Rs.500/- Rs.500/- Rs.500/-

KIMS 26673056 Rs.500/- with replacement

Rs.500/- Rs.500/- NARs.500/- with replacement

Manipal Hospital 25024224 Rs.850/- Rs.650/- Rs.650/- Rs.650/- Rs.650/-

Dr.Shivaji Rao's Blood Bank 22224044 Rs.800/- NA NA NA NA

Jeeva Voluntary Blood Centre 26707755 Rs.700/- NA

AB+ve: Rs.750/-

Negative grp: Rs.900/-

Rs.700/-

Rs.750/-

Rs.900/-

Rs.700/-

Rs.750/-

Rs.900/-

Rs.700/-

Rs.750/-

Rs.900/-

NA

NA

Grace Blood Bank 23336608 Rs.700/- NA NA NARs.700/-

Rs.500/- with replacement

Rs.500/- with replacement

B'lore Lions Service Blood Bank

22266807 Rs.505/- Rs.605/- Rs.605/- Rs.605/- Rs.605/-

Hosmat Hospital 25593796 Rs.850/- NA NA NA NA

Unique Blood Bank Centre 26709970 Rs.700/-

AB+ve: Rs.750/-

Negative grp: Rs.900/-

Rs.700/-

Karnataka Red Cross Blood Bank

22268435 Rs.500/- NA NA NA NA

Navarang Blood Bank & Diag Lab

23521233 Rs.700/- NA NA NA NA

Minerva Blood Bank 26574830 Rs.700/- NA NA NA NA

Life Care Voluntary Blood Bank

25567392 Rs.700/- NA

Akshaya Blood Bank 23523987 Rs.700/-

Rs.700/- Rs.700/- Rs.700/-

Rs.700/- Rs.700/- Rs.700/-

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Transfusions for Anemia – Tread with Caution

Dr. Tanya, Dr. Srividya, Dr. Prakash K. Mehta

Bhagwan Mahaveer Jain Hospital, Bangalore.

Introduction : Anemia contributes to significant morbidity and mortality in India. Up to 80% of

Indian women are anemic. Factors contributing to anemia include nutritional deficiency in pre-

pubertal and pubertal age group, frequent child birth in reproductive age group and

menorrhagia in peri-menopausal age group .Among the management options blood transfusion

plays an important role. However, transfusions need to be given with care and caution. Here is a

case report of a patient who underwent hysterectomy for DUB.

Case : Mrs. X, a 35 year multipara was referred to Bhagwan Mahaveer Jain Hospital for tertiary

care with history of undergoing TAH for DUB four days prior to admission. Patient apparently

had no pre-operative or intraoperative complications. Postoperatively patient was transfused 1

pint O positive whole blood, following which she developed vomiting, breathlessness and

decreased urine output. Post transfusion a fall in Hemoglobin levels was noted and hence she was

transfused 2 more units or O positive whole blood. Patient's condition continued to deteriorate.

She became hypoxic and had renal failure following which patient was referred to our centre.

Patient is P2L2 with last delivery 15 years back and underwent tubectomy .She had menorrhagia

since 2 years. Her past and family history were not significant

On Examination : :General condition : poor, Afebrile, Pallor++, Heart Rate - 60/min ,Blood

Pressure - 140/90 mmHg, RR - 38/min SP02 84%, CVS : S1S2,RS : scattered b/l crepitations +,

P/A Soft wound healthy BS+ , PV - vault healthy, no bleeding PV. Catheter in situ – no urine

draining.

Patient was admitted to ICU. Investigations showed Hb 5.9gm%; PCV 18.4%; Peripheral smear –

features of Hemolysis, Blood urea 167 mg %; Serum Creatinine 2.6 mg%; Na 137 meq/l; K+ 3.4

meq/l; RBS 105 mg%, USG done revealed Normal study. A diagnosis of ARF and hemolysis due

to? transfusion reaction? sepsis considered. A search was made for the precipitating factor Based

on history & investigation reports, mismatched transfusion was considered to be a greater

probability. Samples were sent to blood bank for blood group investigations. On direct matching

the blood group was revealed as O positive. However, on reverse cross matching, she was found

to have Bombay blood group. In view of anuria and rising creatinine, patient was started on

hemodialysis. In view of extreme rarity of Bombay blood group, extreme difficulty encountered

in obtaining cross matched blood. Only 3 pints of blood could be arranged – one from BMJH

blood bank, one from Manipal and one from Mumbai. We could arrange only 3 pints of Bombay

Blood group for the patient. Patient was also given erythropoietin injections in view of limited

availability of blood and with a hope that if the patient survives for a week, then this could take

care of anemia. In spite of all measures, patient's condition continued to deteriorate; she

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developed ARDS and needed ventilatory support. Patient developed Generalized Tonic Clonic

convulsions. CT scan revealed multiple hypodense lesions with hyperdense lesions in Left

Frontoparietal and right parietal region and gross edema -suggestive of venous infracts. Patient

was started on steroids & epsolin. 24 hours later patient arrested and in spite of following all

ACLS protocol, she could not be revived.

Discussion: Individuals with the rare Bombay phenotype (hh) do not express substance H (the

antigen that defines blood group O) on their red blood cells, and therefore do not agglutinate

(bind with) A or B antigens of the ABO blood group system. Instead, they produce antibodies to H

substance (which is present on all red cells except those of hh genotype) as well as to both A and B

antigens, and are therefore compatible only with other hh donors. This rare group was first

identified in Bombay and hence the name. Transfusion of 'O' group blood to these persons would

result in immediate red cell lysis because of the presence of anti H antibodies in the serum of

Bombay Blood Group patients. Therefore blood from only a Bombay Blood Group individual

should be transfused to a Bombay Blood Group recipient. Given that this condition is very rare to

begin with, any person with this blood group who needs an urgent blood transfusion will

probably be unable to get it, as no blood bank would have any in stock. In the above case

morbidity could have been prevented by avoiding blood transfusion. Adequate preoperative

correction of anemia by hematinics, avoiding blood transfusion for treatment of mild to moderate

anemia goes a long way to prevent such mishaps

References:

Handa V, Oza RM, Patel RZ, Zanzarukiya BB, Mukherjee RA. The Oh (Bombay

group)phenotype.J Indian Med Assoc. 1984 Dec;82(12):446-7.

The Bombay group

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ANAEMIA AND PREGNANCY – CASE REPORT

Dr. Premila Phillips, Dr. Sandhya Toppo

Church of South India Hospital, Bangalore

CASE REPORT: Reporting a case of severe anaemia in a primi, 37wks and 5days gestational

age, with preeclampsia and intrauterine growth restriction in latent labour.

v Mrs. ST, a 22 year old, Primi, was referred to C.S.I. hospital, Bangalore on 24.11.06 with

complaints of amenorrhoea of 37 weeks, swelling and pain of both feet for the past 3-4

months and shortness of breath on exertion of 2 months, worsening gradually to

breathlessness even at rest. There was no history suggestive of impending eclampsia.

v She has had 4 antenatal checks at a private clinic.

v At 27 wks, she was treated for threatened preterm labour.

v At 30 wks, she was treated for UTI. BP recorded at that time was 130/90 mmHg.

v At 34 wks, she was started on Tab. Alphadopa 250 mg bd, but no record of BP available. Her

hemoglobin at 34 wks was 4.5 g/dL for which she was treated with oral iron. Her USG at 34

wks was reported as single live intrauterine pregnancy of 29 wks with moderate

oligohydramnios (AFI-6.5 cm). Placenta fundal and posterior in position. No obvious

anomalies. ? IUGR.

v At 37 wks. her BP was 180/80 mmHg. She was also pale and breathless and hence referred the

same day to our hospital.

v The patient does not give any history of menorrhagia or blood transfusions in the past.

ON EXAMINATION

She was moderately built and moderately nourished. She showed gross pallor, was breathless

and had puffiness of face and extremities. Her pulse rate was 112/min and BP 160/90 mmHg. Her

JVP and DTR were normal. Her cardiovascular systemic examination revealed a haemic systolic

murmur which was heard all over her precordium. On abdominal examination there was mild

abdominal wall edema. Uterus 32 wks size, relaxed, cephalic presentation and fetal heart sounds

were regular. On pelvic examination, cervix was 75% effaced and os 3 cms dilated with the vertex

at 0 station

INVESTIGATIONS

Hemoglobin 3.1g/dL

PCV 13.8%

Platelets normal

Peripheral smear revealed microcytic hypochromic anaemia.

Reticulocyte count was 3 %,

Total.bilirubin 1.16mg/dL suggesting mild haemolysis.

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Serum.albumin was 1.7g/dL

S.Uric acid was 6.2mg/dL.

The renal function tests and liver enzymes were normal.

Urine showed albuminuria of 2+ and 50-55 pus cells/hpf .

Ultrasonogram: At 37 wks showed a single viable fetus corresponding to 31 wks. Total

anhydramnios with a expected fetal weight of 1550+/-135 gms.

NST – Reassuring.

MANAGEMENT

3 units of packed red cells were transfused and labor was accelerated with oxytocin. Liquor was

clear. II stage of labour cut short with outlet forceps because of poor maternal efforts and anaemia.

Prophylactic prostadin given at delivery of anterior shoulder. A male baby of 1.7kg with good

apgars was extracted. One unit of packed red cells and one unit whole blood transfused

postnatally. Post natal period was uneventful. BP was 130-150/80-100 mmHg on anti-

hypertensive medication and patient was discharged on the 5th day. Her hemoglobin was 8.7

g/dL at discharge. She was advised to continue oral iron, calcium, protein and antihypertensive

medication and return for follow-up after 3 days.

COMMENT

Anaemia as a factor in pregnancy and childbirth complication kills 585,000 women annually the

worldover. In India anaemia is the commonest medical disorder seen in pregnancy with an

incidence of 40-70%. 85% of Indian women are anaemic due to iron deficiency anaemia. It is a

major contributing factor for maternal / perinatal morbidity and mortality in our country.

Poverty, illiteracy and ignorance lead to malnutrition and in turn anaemia. Severe anaemia in

pregnancy is associated with a high incidence of pregnancy induced hypertension, intrauterine

growth retardation, intrauterine death and preterm labour. Education and elimination of poverty

would go a long way in eradicating this preventable disorder. Women in the reproductive age

should be advised regular antenatal checks, prophylactic haematinics and proper balanced diet

rich in bioavailable Iron.

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PUBERTY MENORRHAGIA – A CASE REPORT

Dr. Arpitha Deepak Singh, Dr. Nita Vasisht,

Church of South India Hospital, Bangalore

CASE

v 19yr old, Miss Poornima has had her primary education and is a tele-caller by occupation

belongs to middle socio-economic status. She has two siblings aged 16 and 13yrs (sisters,

both studying). Her father is a driver by occupation and her mother is a housewife.

HISTORY OF PRESENTING ILLNESS

v Poornima presented to our hospital on 30-10-2006 with complaints of continuous

bleeding P/V since 30.09.2006. This was the first episode of abnormal menstrual

bleeding. For this, she sought medical help at a local clinic, where she was prescribed

hematinics only. Patient also gave history of loss of weight since one month, and related

the same to the excessive bleeding P/V. She had no H/O amenorrhoea prior to the

current menorrhagia cycle. She gave no history of giddiness / nausea / vomiting /

chronic cough / fever / loss of appetite / bleeding per rectum.

MENSTRUAL HISTORY

v Patient attained menarche at 13yrs of age. Her cycles initially were irregular and of the

pattern 1wk/5-6months, with a normal flow. Following this, she has been having regular

cycles, 4days/28-30days, with a normal flow, with no clots / dysmenorrhoea. Her last

menstrual period was on 30-09-2006.

PERSONAL HISTORY

v Patient is unmarried and not sexually active. Patient is a poor-eater as per her mother's

history. She had not been dewormed in the recent past. No history of previous surgeries

/ blood transfusion / tuberculosis / drug intake / bleeding disorders.

FAMILY HISTORY

v No similar history in the family. Her mother and the older of her two sisters have regular

and normal cycles. There is no history of bleeding disorders in the family.

ON EXAMINATION

Patient was moderately built, poorly nourished with a Height of 153cm, weight of 33kg, with a

BMI of 14.6. Her vitals recorded were, Temp: 98.6°F, Pulse rate: 100/min and BP: 120/80mm Hg.

Clinically breasts and thyroid were normal. No bruises / petechiae / pedal edema were found on

examination

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v Pallor: +++ (Conjunctiva / tongue-pale)

v RS: Clear CVS: Flow murmur + JVP: Raised

v PA: Soft, no tenderness / organomegaly

v PV: Bleeding +

v PR: NAD

CLINICAL DIAGNOSIS

v 19ry old poorly nourished girl with severe anaemia (secondary to menorrhagia) in early

failure

INVESTIGATIONS

v Blood groping/typing: “O” Positive

v Hemoglobin: 3.4g/dl

v PCV: 12.1%

v TC: 5,600cells/cmm

v DC: P75%L24%E01%

v Platelets: 2.2L/cmm

v TSH: 1.75mcIU/ml

v BT: 2'30" CT: 12'

v Urine R/M: WNL

v Stool: No ova

v Ultrasonography: Uterus AV, measures 71 x 29 x 48mm, ET: 4mm

Myometrim-N

B/L ovaries N

PERIPHERAL SMAEAR

v Very pale smear showing a marked paucity of erythrocytes,

adequate platelets & somewhat scanty leucocytes

v RBC's are very anisocytic, anisochromic and mildly poikilocytic

with no visible hemoparasites

v A few, single Howel Jolly bodies are seen

v Macrocytes, microcytes, elliptocytes and abnormal shapes are

seen

v WBC's and platelets are morphologically unremarkable

v IMPRESSION: ANAEMIA, VERY SEVERE, CONSISTANT WITH SEVERE IRON

DEFICIENCY OR CHRONIC DISEASE, MILD LEUCOPENIA

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FINAL DIAGNOSIS

v 19ry old malnourished girl with severe iron deficiency anemia, in early failure

TREATMENT GIVEN

v Tab. Tranexaemic acid 500mg 8th hourly x 3days

v Tab. Norethisterone 12th hourly x 21days

v Three units compatible packed cells transfused

v Oral iron x 3months

v Deworming done

v Patient counseling regarding condition and modality of treatment

v Health education regarding diet, general health measures

AT DISCHARGE

v Sense of well-being expressed by patient

v Repeat Hemoglobin: 9.6g/dl

LESSONS LEARNT

v Anaemia is the most common and treatable condition affecting all age groups, more so

the adolescents and pregnant women in our country

v Education and awareness regarding the condition and its prevention, a key factor in

changing the current scenario

v Regular health camps, regular ANC's to detect/investigate the condition early and treat

adequately, a must

v Golden rule to be remembered and to be reinforced…“PREVENTION IS BETTER THAN

CURE!”

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Obstetric Catastrophe leading to anemia

Dr.Bhavana Mishra, Dr.Shah Prarthana, Dr. Prakash K. Mehta

Bhagwan Mahaveer Jain Hospital, Bangalore.

Introduction: Antepartum hemorrhage is still an important cause of maternal death in the

developing countries. The major risk of placenta previa is severe vaginal bleeding and

consequent morbidity related to hemorrhagic shock and prolonged hypotension. Placenta previa

is overwhelmingly a problem of parous women. While it occurs only once in 250 nullipara, it is

more frequent in grand multipara and women with previous cesarean delivery. Here is an

interesting case of BOH, previous LSCS with twin gestation and placenta previa.

Case : Mrs .Y , a 25 yr old G3P2L0D2, was referred to Jain Hospital at 26+5 wks with twin

gestation & APH. She presented to us on 15.12.06 with heavy bleeding per vaginum since that

morning associated with passing of clots and mild abdominal pain. She appreciated fetal

movements well.

Obstetric history: ML: 6 years, non consanguineous, G3P2L0D2 - G! : 4 yrs back, had jaundice

antenataly, vaginal delivery at term, baby died 2 hrs later, cause not known.

G2: 2 yrs back, H/O placenta previa & LSCS for IUD at 7th month. She had PPH and was

transfused 5 units of blood. G3: LMP: 12/6/06 EDD: 19/3/07. H/O spotting twice in the 2d

trimester, diagnosed as placenta previa. When she had the third episode, she was admitted to a

near by hospital where she was transfused one unit of whole blood and discharged.

On examination: Pallor ++, Tachycardia (HR- 110/min), BP 100/60 mmHg.

P/A examination vertical scar+, uterus 32 wks size, with multiple fetal parts, no scar tenderness.

FHR +/+. PS: Bleeding ++ Clots +.

NST: Reactive for both fetuses. Scan done to confirm diagnosis of placenta previa and estimation

of fetal weight. Hemoglobin: 7.2gm%. Patient underwent emergency LSCS in view of BOH,

previous LSCS, placenta previa with twin gestation after rescue steroiding and arranging for

blood. Lower segment thinned out and vascular. Placenta cut through and two male babies

weighing 870 and 850 grams extracted. Both babies shifted to NICU. The first twin had TEF Type

II and expired on fourth post natal day. The second twin was ventilated stabilized and finally

discharged at the end of 6 weeks.

Patient transfused 2 units of whole blood and repeat hemoglobin was 8.4gm% hence no further

transfusion given. She was discharged on day 6 with advice to continue haematinics.

Discussion: The dilemma we faced while managing this case was about the decision to go ahead

and deliver the babies. There were no records available regarding patient's previous pregnancies.

Considering her H/O previous neonatal death and IUD, a decision had to be made, especially in

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face of bleeding placenta previa, twin gestation and anemia.

Adequate support from blood bank is pivotal in management of patients with late pregnancy

bleeding to avert maternal morbidity and mortality. Facilities for immediate cesarean section,

neonatal resuscitation and intensive care are critical for the management of such patients. Early

transfer of patients to a tertiary centre results in a better maternal and neonatal outcome.

Bibliography: Archibong EI, Ahmed el SM. Risk factors, maternal and neonatal outcome in

major placenta previa: A prospective study. Ann Saudi Med. 2001 May-Jul;21(3-4):245-7.

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A CASE OF ANAEMIA DUE TO THYROID DEFICIENCY

Dr. Parimala Devi

CASE HISTORY:

Patient aged 32 yrs., P2 with 2 LSCS was often treated for anemia.

She underwent Cesarean Section for 1st pregnancy with preterm PROM as indication. She did

well in the postnatal period. However, she would always have excessive menstrual bleeding

lasting for 5 to 7 days and was treated symptomatically. Soon she dropped her hemoglobin and

was given iron supplements.

She got an IUCD inserted but got it removed within a few months due to menorrhagia.

She was pregnant again and underwent repeat LSCS. Post operative period was uneventful.

Soon she resumed periods. She again had menorrhagia and was put on progestogens. USG

showed normal study.

She never improved with routine line of management, and she became quite pale and blood

transfusion was given to correct hemoglobin.

Detailed biochemical test revealed THYROID DEFICIENCY and correction of the same

controlled the menorrhagia.

Patient improved dramatically.

KEY POINTS:

Anemia secondary to hypothyroidism is common.

About 10 – 12% of DUB is due to hypothyroidism.

It is therefore important to investigate a case of resistant anemia, for thyroid deficiency too.

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