HEMATOLOGY CONFERENCE

Cruz, Kristen, Cruz, Riza, Cudal, Beinjerinck Ivan, Dancel, Jonathan

Carlo, Dans, Kunny, Daquilanea, Michee Grace

General Data

• S.G• 4year old• Female• Birthday:• Novaliches Q.C• Informant: Mother• Reliability: Fair

Chief Complaint

PALLORPALLOR

HISTORY OF PRESENT ILLNESS

HISTORY OF PRESENT ILLNESS

HISTORY OF PRESENT ILLNESS

ADMISSION

Review of systems

• No weight loss• No pruritus, cyanosis• no easy fatigability• No abdominal pain, no constipation• No dysuria, oliguria• No loss of consciousness, seizures,

alteration in mental status

Maternal History

Gestational History

• Born to a 35 year old G4-P3, 3-0-0-2• (+) prenatal check-up since 1st month AOG• Hepatitis and gestational diabetes screening was

not done • denies of any exposure to infections and

roentgen studies. • Vitamins: Ferrous Sulfate, Multivitamins• UTZ: (7th , 9th month)

Neonatal History

• Birth– Patient was born term– AGA unrecalled, BW 4 lbs– unrecalled APGAR but claimed to be generally

stable. – No Newborn screening

Feeding History

Feeding- Birth- 1 year: exclusively breast feeding- 8 months: complementary feeding- 1year : chocolate drink- eats everything except vegetables

Personal History

Past IllnessesSept. 2009 – Dengue Fever, PICUNo history of trauma nor prior injuries.No history of prior surgeries.

Personal History

• Immunizations– BCG– Hepa B– DTP – OPV – Measles – Hib – MMR – Varicella– Typhoid

Growth and Development

Developmental milestones Social smile – more than 4 months Head control – more than 4 month old Sits alone – more than 5 months Roll over – 4 months Walks alone – 1 year Runs – 2 years Feeds self with crackers – 6 months First words – 11 months Toilet train: 3 years Scribbles: 2 years

Present assessment:

Family ProfileAge Educational

AttainmentOccupation Health Status

Father 42 High school Laborer Apparently healthy

Mother 39 Vendor/housewife

Apparently healthy

Nel Patrick 18 2nd year college

Apparently healthy

Mark Darwin 11 Grade 5 Apparently healthy

Tracy 9 Deceased Apparently healthy

Family History

• (+) Hypertension • (+) Cardiac disease – grandmother• (+) Asthma – father side• β- Thalassemia – sister• (-) bleeding disorders• (-) PTB• (-) Diabetes mellitus• (-) Kidney Disease

Socio-economic Profile

• The patient lives in a bungalow, owned, made of wood with her parents and siblings.

• The father is the breadwinner while the mother is the primary caregiver.

• Water source for drinking is NAWASA• They don’t have any pets but there are stray

dogs, chicken and a piggery in their neighborhood.

• The garbage is collected twice a week and they practice waste segregation.

Physical examination

• Awake, alert, ambulatory, no signs of dehydration, not in cardiorespiratory distress, well-nourished, well-developed

• BP 90/50 HR100 bpm, reg RR24 cpm T36.3C,• wt 14.7kg (z=-1), ht 94.5cm (Z=below -2)• Warm moist skin, pale, no jaundice, no cyanosis, no

rashes• Atraumatic head, normocephalic, frontal bossing• Pale palpebral conjunctivae, anicteric sclera, pupils 2-

3mm ERTL

• Nasal septum midline, no nasal congestion, no tragal tenderness, (-) aural discharge

• Moist buccal mucosa, midline uvula, nonhyperemic posterior pharyngeal wall, tonsils not enlarged

• Supple neck, thyroid not enlarged, (+)cervical lymphadenopathy

• Symmetrical chest expansion, no retractions, clear breath sounds

Physical examination

• Adynamic precordium, no murmurs• Globular abdomen, NABS, soft, nontender, no

palpable masses, liver span 12cm, (+)splenomegaly

• Straight spine, no deformities• No edema, no cyanosis, no clubbing• Pulses full and equal on all extremities, pale

nail beds

Physical examination

Neurologic Examination

Cerebrum: Awake, alert, GCS 15Cranial nerves: I – XII intact

Motor: 5/5 on all extremities, No tremors, atrophy, fasciculationsReflexes: DTR’s 2+, (-) BabinskiMeningeal signs: No nuchal rigidity

PRESENTING MANIFESTATIONS

• Low hemoglobin • Low hematocrit• (+)splenomegaly• Pallor• (+) family history

Approach to Diagnosis• Signs and Symptoms or Laboratory findings

pathognomonic of a disease• SSigns and Symptoms or Laboratory findings igns and Symptoms or Laboratory findings

pointing to an organ or part of an organ systempointing to an organ or part of an organ system• Signs and Symptoms or Laboratory findings

pointing to a group of diseases• Signs and Symptoms or Laboratory findings

whose mechanism is well understood• Signs and Symptoms or Laboratory findings found

in the least number of disease

Harrison’s Principle of Internal Medicine 17th edition

b-Thalassemia minor (heterozygous

• mild hypochromic anemia• normal serum iron• increased red cell number• Ratio of mean red cell

volume (MCV) to red cell count is <13

• Increased HgA2

b-Thalassemia major (homozygous)

• severe hypochromic anemia with microcytosis anisocytosis, and poikilocytosis by 12 months.

• Mild ↑serum indirect bilirubin

• Hb electrophoresis shows only Hb F and A2

COURSE IN THE WARDS

On admission• CBC requested• Pre-BT medications:

– Paracetamol 250mg/5ml (3ml)

– Diphenhydramine 12.5mg/5ml (10ml)

• Transfused with properly typed and crossmatched 1’u’ pRBC divided into 2 satellite bags

2nd HD• Applied to SAGIP• Given Deferroxamine

500mg/vial OD x 5 days– Reconstitute 1 vial of

Desferroxamine with 2 ml sterile water. Once dissolved add 8ml PNSS to make 10mL solution then give per subcutaneous infusion over 12 hours

3rd and 4th HD• Patient was stable

5th HD

COURSE IN THE WARDS

Laboratory Results11/24/09 Reference value

White Blood Cell 7.73 x 10^9/L 4 -12

Red Blood Cell 3.00 x 10^12/L 4 – 5.30

Hemoglobin 64 g/L 115 – 145

Hematocrit 0.198 0.33 – 0.43

MCV 66.00 fL 79.40 – 94.80

Mean Corpuscular Hb 21.30 pg 25.60 – 32.20

Mean Corpuscular Hb Conc. 32.3 % 32.20 – 35.50

RBC Distribution Width 21.30 % 11.60 – 14.60

Platelet Adequate

Neutrophils 0.49 0.35 – 0.55

Lymphocytes 0.36 0.25 – 0.46

Monocyte 0.10 0.00 – 0.08

Eosinophil 0.05 0.00 – 0.06

11/23/09 Reference value

Creatinine 23.29 umol/L 26.55 – 61.95

SGPT/ALT 101.98 U/L 10 - 25

Ferritin > 2000 ug/L 13 - 150

Laboratory Results

TREATMENT

• Before chronic transfusions are initiated, the diagnosis of β0-thalassemia should be confirmed and the parents counseled about this lifelong therapy.

• Initiating transfusion and chelation therapy can be difficult for parents to face early in their child's life.

• Before transfusion therapy is begun, a red cell phenotype is obtained; blood products that are leukoreduced and phenotypically matched for the Rh and Kell antigens are required for transfusion.

• If there is the possibility of a bone marrow transplant, the blood should be negative for cytomegalovirus and irradiated.

• Transfusion therapy promotes general health and well-being and avoids the consequences of ineffective erythropoiesis.

• A transfusion program generally requires monthly transfusions, with the pretransfusion hemoglobin level >9.5 and <10.5 g/dL.

• In patients with cardiac disease, higher pretransfusion hemoglobin levels may be beneficial. Some blood centers have donor programs that pair donors and recipients, decreasing the exposure to multiple red cell antigens.

TREATMENT

• Transfusional hemosiderosis causes many of the complications of thalassemia major. – Transfusional hemosiderosis can be prevented by the use of deferoxamine

(Desferal).

• Accurate assessment of excessive iron stores is essential to optimal therapy. – The serum ferritin level is useful in assessing iron balance trends, but does

not accurately predict quantitative iron stores. – Undertreatment or overtreatment of presumed excessive iron stores can

occur when a patient is managed based on the serum ferritin level alone.

• Measurement of the iron level by liver biopsy is the standard method for accurately determining the iron store. – Although quantitative liver iron measurement accurately guides the use of

iron chelators, it may not reflect cumulative changes in cardiac iron.

TREATMENT

• A ferritometer and specialized MRI software are emerging alternatives for liver biopsies.

• Patients can have cardiac iron overload at the time of a safe liver iron measurement.

• Many thalassemia centers monitor cardiac iron with T2 weighted MRI imaging, but routine application of this technology has not been implemented across all sites.

TREATMENT

• Deferoxamine chelates iron and some other divalent cations, allowing their excretion in urine and stool.– Deferoxamine is given subcutaneously over 10–12 hr, 5–6 days a

week. – Side effects include ototoxicity with high-frequency hearing loss,

retinal changes, and bone dysplasia with truncal shortening. – The number of hours deferoxamine is used daily is more important

than the daily dose. – High-dose, short-term infusions increase toxicity with little efficacy.

P– lasma non-transferrin-bound iron (NTBI) is most likely responsible

for the serious iron injury. When deferoxamine is infusing, it binds NTBI.

– The 24 hr deferoxamine infusion has been shown to reverse cardiomyopathy in patients with excessive iron stores in the heart that result in symptomatic congestive heart failure.

TREATMENT

• Deferiprone is a new iron chelator approved by the U.S. Food and Drug Administration for children >2 yr of age (see Chapter 462.1 ).

– Deferiprone may not be as effective as deferoxamine in total body iron chelation, but may be more effective in removing cardiac iron.

– Side effects include neutropenia, and weekly blood counts are needed.

• Other iron chelators are being studied for oral and subcutaneous use.

• ICL670 is an oral chelator that appears effective in phase III trials and may be approved for use in the U.S. in the near future.

• Bone marrow transplantation has cured >1,000 patients who have thalassemia major.

– Most success has been in children younger than 15 yr of age without excessive iron stores and hepatomegaly who have HLA-matched siblings.

– All children who have an HLA-matched sibling should be offered the option of bone marrow transplantation.

TREATMENT

DISCUSSION

Thalassemias

-genetic disorders in globin chain production -β-thalassemia- either a complete absence of

β-globin gene production (β0-thalassemia) or a partial reduction (β+-thalassemia)

- α-thalassemia - α-globin gene production is either absent or partially reduced

EPIDEMIOLOGY

Approximately 20 common alleles constitute 80% of the known thalassemias worldwide

3% of the world's population carries genes for β-thalassemia

Southeast Asia, 5–10% of the population

carries genes for α-thalassemia

THALASSEMIA

• autosomal recessive blood disease.• the genetic defect results in reduced rate of

synthesis of one of the globin chains that make up hemoglobin.

• Reduced synthesis of one of the globin chains can cause the formation of abnormal hemoglobin molecules, thus causing anemia,

Overview

Hemoglobin– oxygen-carrying component of the red blood cells– consists of two different proteins

• alpha • beta.

Alpha Thalassemia• Four genes (two from each parent) are needed to

make enough alpha globin protein chains. • commonly found in Africa, the Middle East, India,

Southeast Asia, southern China, and occasionally the Mediterranean region.

• types– Silent Carrier State. – Alpha Thalassemia Trait or Mild Alpha Thalassemia. – Hemoglobin H Disease. – Hemoglobin H-Constant Spring. – Hydrops Fetalis or Alpha Thalassemia Major

Cooley's Anemia Foundation, Inc.

PATHOGENESIS OF Alpha THALASSEMIA

• relatively fewer α-globin • an excess of β- and γ-globin chains.• These excess chains form

– Bart's hemoglobin (γ4) in fetal life – Hb H (β4) after birth.

• Prenatally, a fetus with α-thalassemia may become symptomatic because Hb F requires sufficient α-globin gene production,

• whereas postnatally, infants with β-thalassemia become symptomatic because Hb A requires adequate production of β-globin genes.

Inheritance Pattern for Alpha Thalassemia

Beta Thalassemias

• People whose hemoglobin does not produce enough beta protein

• It is found in people of Mediterranean descent, such as Italians and Greeks, Arabian Peninsula, Iran, Africa, Southeast Asia and southern China.

Pathogenesis of Beta Thalassemia

• Inadequate β-globin gene production– leading to decreased levels of normal hemoglobin

(Hb A)

• imbalance in α- and β-globin chain production.

Types of Beta Thalassemia

Types of Beta Thalassemia

Inheritance Pattern for Beta Thalassemia

CLINICAL MANIFESTATIONS

• If not treated, children usually become symptomatic as a result of progressive hemolytic anemia,

• with profound weakness and cardiac decompensation during the 2nd 6 mo of life.

• Most infants and children have cardiac decompensation when the hemoglobin is 4.0 g/dL or less.

SummaryNumber of

affected genesHemoglobin

(g/dL)MCV (fL) Transfusion

dependent

Alpha Thalassemia

Alpha-thal-2 trait 1 NORMAL None No

Alpha-thal-1-trait 2 >10 <80 No

Hemoglobin H 3 7-10 <70 +/-

Hydrops Fetalis 4 Incompatible with Life

Beta-Thalassemia

Beta-Thal Minor (trait)

1 >10 <80 No

Beta-Thal intermedia

2 7-10 65-75 +/-

Beta-Thal Majot 2 <7 <70 yes

DESFEROXAMINE

INDICATION- for the treatment of chronic iron overload due to blood transfusion (transfusional hemosiderosis

GOAL- iron chelation therapy- removed the amount of iron administered in transfusion

INDESIRABLE EFFECT• GI disturbance 26%• Skin rash 7%