Dr Mere Kende

MBBS, MMED (Path), MACTM, MAACB, MACRRM

Lecturer: SMHS

Topics Anaemia

Iron Deficiency

Vitamin B12 deficiency

Hemolysis

Haemoglobinopathies

Petechiae/Bruising

Coagulopathies

Neonatal Jaundice

Leukaemia

Clinical Presentation of Hematological Disorders Asymptomatic

Non-specific symptoms

Poor Growth /Nutritional Issues

Anaemia

Jaundice

Skin bruising

Haematuria

Lympadenopathy

Joint Swelling

Organomegaly

Anaemia Definition: Hb <lower Limit of reference range for

age

Age LL of normal Range (g/L)

24hrs 120-160

2months 90

2-6months 95

6-24months 105

2-11years 115

>12 years girls 120 boys 130

Changes in Hb after Birth

Hb g/L 220 200 180 160 140 120 100 80 60 40

Birth 24hours 3months 6months adult

[Hb] at birth: 160-190g/L.

It rises transiently in the first 24 hours

Slowly falls to as low as 95 g/l by the 9th week.

By 6 months, Hb stabilises at around 125 g/l, the lower end of the adult range,

Then increases towards adolescence.

PREMATURE BABIES Fall in Hb is accelerated may fall to less than 90

g/l by the 4th week .

Prone to multiple nutritional deficiencies because of rapid growth.

Anaemia is worse if the infant gains insufficient weight or is fatigued while feeding.

Clinical Features (NON-SPECIFIC) Poor Feeding/intake

Pallor

Pale conjunctivae

Flow murmur

Lethargy

Poor growth

Signs of cardiac failure

Listlessness

SOB

Anaemia associated with infection HIV

Malaria

CMV & rubella,

Toxoplasmosis,

congenital syphilis -rarely

Parvovirus B19 (BM aplasia)

Cause: haemolysis or BM suppression.

HIV infection

Causes chronic multisystem

Perinatal transmission – 20-40% of Pregnancies

Thrombocytopenia occurs in up to 15% of children with HIV infection

Normocytic, Normochromic Anaemia is common

Leucopenia and lymphopenia are also seen, in which the BM shows non-specific features of chronic infection

Investigation of Anaemia

FBE

Blood Film Exam

Ferritin/Iron studies

Reticulocyte Count

Causes: Classification –based on MCV

Microcytic

(Low MCV)

Serum Ferritin

Low

Iron Deficiency

Normal

Hb Electrophoresi

s

Thalassaemia minor

Normocytic (Normal MCV)

Reticulocyte Count

Increased

Hemolysis/ Blood Loss

Low/Normal

Marrow hypoplasia/ leukaemia/infiltrate

Macrocytic (high MCV)

Serum & red cell folate

Serum B12

Normal

Myelodysplasia, Fanconi’s Anemia, TC II deficiency

Reduced

B12/folate Deficiency

Iron Deficiency Anaemia Commonest cause of anaemia

throughout the world

May be subclinical -role cognitive and psychomotor development

Leads to anaemia in those with severe deficiency

Present in 10-30% of children in high risk groups

Most due to inadequate dietary intake

Lost through cow milk provoked GIT loss in infants/worm infestation & menstruation in adolescent girls

Children at High Risk for iron Deficiency Anaemia Group/Age Additional Risk Factors

mechanism <6months Prematurity Inadequate Stores

LBW/Multiple Births Maternal iron deficiency 6-24months Exclusively Breastfed Inadequate Intake Delayed introduction of iron containing food Excessive Cow milks Adolescent Females Menstrual loss Poor Diet Rapid Growth Spurt Socially Disadvantaged Worm Infection Fad diets/ Vegeterians Poor diet Inadequate Intake

Diagnosis Hypochromic , microcytic blood film, Low iron and

Ferritin and raised TIBC and transferrin

Ferritin is acute phase reactant

Early sign reduced ferritin & FBE can be normal

Remember low iron due to poor diet may be associated with other micronutrient deficiency

Empiric iron treatment may be a strategy

Treatment

Supplement iron

Iron as ferrous gluconate mixture 1ml/kg (300mg/5ml prep)

Continue 3 months after Hb has normalised to replenish iron stores

Transfusion may be indicated if heart failure/severe infection/if urgent surgery is needed

Stools may become black/grey

Note: iron overload is fatal- advise locked cabinet

Prevention of Iron Deficiency Introduce iron containing food at 4-6 months

Avoid cows milk in the first 12months(small amounts allowed in custards, cereal, etc)

Cows milk should only form small part of diet up to 2 years of age

Ensure that formulas (if used) and cereals are iron fortified

Consider supplements in high risk groups

Good Sources of Iron Infant milk formula

Fortified breakfast cereals

Meat (red meat/chicken/fish)

FGLV

Dried beans and fruits

Egg york

Food rich in Vitamin C increases iron absorption from non-meat sources

Vitamin B12 deficiency Presents commonly in 1st 2 years of life

Commonly nutritional due to maternal B12 deficiency

Presentation: neurological abnormalities +macrocytosis + pancytopenia + hypersegnmented neuophils

Should be urgently diagnosed and treated due to lack of reversibility of neuro symptons/signs

BM –shows megaloblastic Changes

FBE:

Anaemia- mild to severe

Elevated MCV

Normal MCV can occur with B12 deficiency

Caution : co-existing iron defciency /thalassaemia (normal MCV)

Blood Film:

hypersegmented neutrophils (3-4 lobes)

anisocytosis and

poikilocytosis

macro-ovalocyte,

low reticulocytes

Pancytopenia (severe cases)

Bone Marrow Aspirate-Megaloblast

This hypersegmented neutrophil is present along with macro-ovalocytes in a case of pernicious anemia. Compare the size of the RBC's to the lymphocyte at the lower left center. Note that the large RBCs lack a zone of central pallor.

Lymphocytes

Macro-ovalocytes

Measure serum vitamin B12

Methyl Malonic Acid-measured as indicator of early B12 deficiency (HPLC)

Acute Hemolysis May require admission & transfusion

May present with non-specific symptoms

Haemolytic disease in newborn infants Immune hemolysis by antibodies from the mother that cross the placenta.

Rhesus D antibodies to RhD antigen.

Prevention: Immunise mother with anti-D immunoglobulin.

Anti-D immunoglobulin is administered to non-sensitised RhD

negative women,

Mortality 40% if baby affected

Treatment : exchange transfusion improves survival rate by 85%.

Recommendations for prophylactic anti-D immunoglobulin in RhD negative women After delivery if the infant is Rh positive

After abortion (therapeutic or spontaneous)

To cover antenatal procedures (amniocentesis, chorionic villus sampling)

After threatened abortion or miscarriage

Antenatally at 28 and 34 weeks (not yet universal)

Reasons for failure of prophylaxis Failure of administration (commonest cause)

Inadequate dosage (routine Kleihauer tests should be

performed)

Earlier sensitisation that may not be detectable at birth

Poor injection technique (should be deep IM)

General Features of Acute Hemolysis Anaemia/Pallor/Jaundice

+/-Hepatospenomegaly

Reticulocytosis

Unconjugated hyperbilirubinaemia

Raised AST/LDH

Haemoglobinaemia

Haemoglobinuria

Raised urobilinogen in Urine

No bilirubinuria (unconjugated/insoluble)

Raised MCV -Early nucleated Red cells

Haptoglobin (less useful in children)

Acute Hemolysis Anaemia/Reticulo

cytosis

Extrinsic

Antibody Mediated

Microangipathic

Infective

Intrinsic

Membrane Disorder

Enzyme Disorder

Hb Disorder

Intrinsic

Membrane

Hereditary

Sperecytosis/Ovalocytosis

Enzyme

G6PD Deficiency

Pyruvate kinase deficiency

Hemoglobinopathies

Thalassemia

Unstable Hb

Sickle Cell

Hemoglobinopathies β-globin thalassemia

α- globin thalassemia

Sickle Cell Anemia

Others: Hemoglobin C/E

Thalassemia

Thalassemia Normal Hb (2 2)

Individuals inherit one gene from each parents compared

to two genes

Alpha thalassemia- alpha chain defect/gene deletion Silent carrier ( -/) Alpha-thalassemia trait ( -/ - ) or (--/) Hb H Disease (- -/ -) or lacks 3 alpha genes Hydrops Fetalis /IUD(- -/- -) -Hb Barts (4) or lacks all 4

alpha genes

- Thalassemia- beta chain defect/reduced beta chain

amount/qantitative defect

-Thalassemia Major (inadequate -chain)

Marked relative excess of α- chain

Uncommon in 1st world due to increased antenatal screen & prenatal termination

Symptoms begin second 6 months of life [switch of HbF (22) - HbA1 (2 2) during 1st 6months]

Presentation: severe hemolytic anaemia, slow growth,

skeletal deformities, hepatosplenomegaly (always), heart failure

hypochromic, microcytic anaemia, PCV <20%: Normal/high Fe++

Blood Film in Beta Thalassaemia

This peripheral blood smear shows marked poikilocytosis (abnormally shaped RBC's) as well as some anisocytosis (variation in RBC size), though many are small (microcytes). This patient has beta-thalassemia, a hereditary disorder of beta globin chain synthesis that leads to ineffective erythropoiesis and a microcytic anemia. Some of these abnormally shaped RBC's resemble jigsaw puzzle pieces.

Excess alpha chains Increased HbF (22) a &

2-fold increase in HbA2 (22)

Depend on transfusion

Reduced life expectancy

Iron Overload

Genetic Counselling/Antenatal diagnosis

Bone Marrow Transplant

Beta-Thalassemia Minor (Thalassemia trait)

very common

Rarely show significant anaemia and symptoms

Causes microcytic, hypochromic Anaemia

Clues on FBE include elevated RBC count/marked microcytosis

Diagnosis: Hb electrophoresis- elevated HBA2

Often treated unnecessarily with iron

HbA2 levels may be corrected with iron therapy obscuring the dx

Alpha Thalassemia AT /Trait is

1 or 2 gene deletions

relatively common in Asian populations

Asymptomatic throughout life

Microcytosis /target cells may be seen

Hb electrophoresis –normal except decreased HbA2

HbH –3 gene deletions

microcytic but asymptomatic when well

May develop anaemia when stressed

DDx

G6PD

Blue Inclusions (methylene Blue)

Hydrops Fetalis- Hb Barts -4 gene deletion

Generalized edema from fluid collection in the soft tissues results in hydrops fetalis. Incompatible with life Other Causes: Infections Cardiac Failure Rh Incompatibility

Sickle Cell Anaemia

Abnormal Hb SS is prone to form crystals when oxygen tension is low, and the RBC's change shape to long, thin sickle forms that are "sticky" and sludge in capillaries, further decreasing blood flow and oxygen tension. The sickled RBCs tend to adhere to endothelium, and the bioavailability of endothelial nitric oxide is reduced as well, further promoting vaso-occlusion.

Sickle Cell Anemia Homozygous (ss) or double heterozygous (HbS/b-thalassemia)

Defect in beta chain: substitution of valine for glutamic acid at

6th residue of beta chain

Deoxygenated HbS cell sickles easily from biconcave disk to elongated crescent-shaped or sickled cell—

Lack flexibility and rigid to transverse capillaries ---hemolysed

8% black Americans

Up to 30% Central Africa (associated with malaria endemic areas)

Gives slight protection from malaria

Clinically Asymptomatic carrier

Symptoms –onset at 6 months of age (HbFHbA switch)

Multiple systems Disease

CNS/Resp/skin/eyes/GUT/MSS etc

Anaemia (hemolysis/aplasia)

Reduced RBC half-life (10-15 days)

Rapidly progressive anaemia with splenomegaly

Delayed growth & Development

Acute Chest syndrome (pneumonia-like)

Arterial ischaemia stroke

Painless haematuria

Painful crisis (joint/abdomen)

Sepsis/Sickling crisis in carriers– if severely hypoxic

Diagnosis Blood Film-

demonstrate sickling under reduced oxygen tension Normocytic, normochromic anaemia, Target cells

Hb Electrophoresis- Hb S 76-96% HbF 2-20% HbA2 2-4% HbA1- 0%

HbS Heterozygotes- minimal problems, normal Life

expectancy

Treatment Supportive

Conservative

Antenatal Counselling

Prenatal Diagnosis (DNA analysis)-CVS/AFS

Acute Hemolysis

Extrinsic

Ab -mediated

Coomb’s +ve autoimmune, ABO/Rh-related, Drug

Induced, Cold Agglutinins,

T-antigen activation

Microangiopathy

HUS

TTP

DIC

Post-heart valve

Infections

Malaria

Severe Sepsis

Autoimmune Hemolytic Disease

Mechanism of antibody-mediated immune destruction of red cells

Acquired disorder

Production of IgG autoantibody against RBC membrane antigens.

IgG most commonly directed against ABO and Rhesus antigen

Mechanism Red Cell is first coded by IgG-

- recognised by RES/Spleen –removal of RBC membrane -formation of spherocytes - removal of RBC by RES --> Hemolysis

General Considerations

Used to diagnose AUTOIMMUNEHEMOLYTIC ANAEMIA.

Coomb's reagent

Is a rabbit IgM antibody raised against human IgG or human complement.

Direct Coomb's test -

mix the patient's red blood cells with the Coomb's reagent

Positive Agglutination

Presence of bound antibody on patient’s RBC surface.

Coomb’s Anti-globulin test

Indirect Coomb's test

Mixing the patient's serum with a panel of type O red blood cells.

Incubate test serum and panel O red blood cells,

Add Coomb's reagent

Positive Agglutination

Presence of free antibody in the Patient's serum.

Essentials of Diagnosis

Microangiopathic hemolytic anemia.

Thrombocytopenia and renal failure.

Normal coagulation tests.

Follows gastro (E.Coli)

Absence of neurologic abnormalities (cf. TTP)

Complete recovery /Good prognosis

Haemolytic Uraemic Syndrome

Lab Investigation of Hemolysis

Blood Film

spherocytes-hereditary

Target cells-Thalassemia

Hypochromia/microcytosis-Thalassemia

Fragmented cells-MAH

Direct Coomb’s test-autoimmune HA

Hemolysis-Reticulocytosis

This peripheral blood smear demonstrates many larger bluish reticulocytes as well as smaller RBC's lacking central pallor--spherocytes. This patient had an autoimmune hemolytic anemia. Antibody coated the RBC's, and portions of the RBC's were removed, decreasing cell size. Many RBC's were removed entirely, resulting in anemia and a bone marrow response with increased erythropoiesis and elevated reticulocyte count (20%). The patient developed an indirect hyperbilirubinemia as well.

Thalassemia

This peripheral blood smear shows marked poikilocytosis (abnormally shaped RBC's) as well as some anisocytosis (variation in RBC size), though many are small (microcytes). This patient has beta-thalassemia, a hereditary disorder of beta globin chain synthesis that leads to ineffective erythropoiesis and a microcytic anemia. Some of these abnormally shaped RBC's resemble jigsaw puzzle pieces

Spherocytosis -Hereditary

The size of many of these RBC's is quite small, with lack of the central zone of pallor. These RBC's are spherocytes. In hereditary spherocytosis, there is an abnormality of RBC cytokeletal membrane proteins such as ankyrin and spectrin. This produces membrane instability that forces the cell to the smallest volume--a sphere. In the laboratory, this is shown by increased osmotic fragility. The spherocytes do not survive as long as normal RBC's

Intra-vascular Hemolysis (DIC)

There are numerous fragmented RBC's seen here. Some of the irregular shapes appear as "helmet" cells. Such fragmented RBC's are known as "schistocytes" and they are indicative of a microangiopathic hemolytic anemia (MAHA) or other cause for intravascular hemolysis. This finding is typical for disseminated intravascular coagulopathy (DIC).

Viral Infection

The WBC's seen here are "atypical" lymphocytes. They are atypical because they are larger (more cytoplasm) and have nucleoli in their nuclei. The cytoplasm tends to be indented by surrounding RBC's. Such atypical lymphocytes are often associated with infectious mononucleosis from Epstein-Barr virus (EBV) infection

Toxicity –Basophilic stippling

The nucleated RBC in the center contains basophilic stippling of the cytoplasm. This suggests a toxic injury to the bone marrow, such as with lead poisoning. Such stippling may also appear with severe anemia, such as a megaloblastic anemia.

Specific Tests

Heinz Body stains-unstable Hb,

G6PD Assay-

Hb electrophoresis- thalassemia/Sickle Cell

Further Test –in consultation with specialist

Coagulopathies Can present anytime

Bruising of varying ages, unusual sites

Positive Drug hx

Positive Family hx

Previous bleeding episodes/problems at surgery/tooth

extractions Coagulation studies (child)–not routine unless clinically

indicated

Major Coagulopathies

Haemorrhagic Disease of Newborn

Idiopathic /Immune thrombocytopenic purpura (ITP)

Haemophila A & B (Christmas Disease)

Von willebrand disease (vWD)

Vitamin K deficiency Causes haemorrhagic disease in newborn infants

It may present soon after birth with generalised bruising

and internal bleeding, or as late as age one month.

It may be seen in otherwise healthy term infants , especially if they are being breast fed.

Precipitated if the mother is taking anticonvulsant drugs or warfarin.

Treatment: Vitamin K prophylaxis at birth

Other causes of purpura

Septicaemia/meningococcus

Enterovirus

Henoch-shonlein pupura

Leukaemia

Child abuse

Trauma/vasomotor straining

Parvovirus B19/Fifth Ds/Erythema infectiosum

‘Slapped cheek’

Thrombocytopenia Ref Range: (150-400000/L).

most common haemostatic abnormality in newborn

infants, occurs in 25% in NICU.

Commonest causes: Asphyxia at birth, infection, and DIC.

Can occur following exchange transfusion.

Platelet transfusions should be given to any infant whose count is 20 000/L.

Maternal ITP may be associated with neonatal thrombocytopenia because of placental transfer of anti-PLT antibodies.

Fetal platelet counts rarely drop below 50000/l, and intracranial haemorrhage is rare either prenatally or at birth.

There are no reliable predictors of severe thrombocytopenia.

Treatment: PLT transfusions & steroids; IV immunoglobulin is safe & effective in over 80% of infants.

Common causes of thrombocytopenia

Immune mediated

Neonatal ITP Maternal ITP Drug-induced

Infection Viral—eg cytomegalovirus, HIV, rubella Toxoplasmosis

Post exchange transfusion Disorders of haemostasis

DIC/hypthermia/hypoxia Maternal pre-eclampsia Rhesus isoimmunisation Type IIB von Willebrand’s disease

Liver disease Marrow infiltration

Idiopathic thrombocytopenic purpura (ITP), Synonyms: primary Immune P & autoimmune TP

Definition:

isolated thrombocytopenia

normal bone marrow and

no identifiable cause .

Two distinct clinical syndromes

acute condition in children

chronic condition in adults.

Cause

Immunoglobulin G (IgG) autoantibodies on the platelet surface

Increased peripheral platelet destruction

Low platelet count + absence of toxic exposure or a disease

Precipitating Factors Acute ITP (infection) and has a spontaneous

resolution within 2 months.

Chronic ITP (adults) persists longer than 6 months without a specific cause.

Sex

Incidence : Acute ITP (children),M=FM .

Age

Peak age: 2-4 years.

~ 40% younger than 10 years.

Children commonly than adults

Common signs, symptoms, and precipitating factors include the following Abrupt onset (childhood ITP)

Purpura /Epistaxis

Gingival bleeding

Recent live virus immunization (childhood ITP)

Recent viral illness (childhood ITP)

Bruising tendency

Physical

Skin-bruises/purpura

Non-palpable petechiae, which mostly occur in dependent regions

No sign of liver Disease

No sign of DIC/vasculitis

Check for sign neuro sign (IC bleeding)

Spontaneous bleeding when platelet count is less than

20,000/mm

Differential Diagnoses DIC

HIV Infection and AIDS

Other Problems Pseudothrombocytopenia (PLT

clumping in EDTA tube) Myelodysplasia Lymphoproliferative, autoimmune,

or infectious ds Drug-induced Infection/sepsis/Acute leukemia Megaloblastic anemia Isoimmune neonatal purpura Transfusion

Factitious Vasculitis (PAN)

Laboratory Studies CBC

Isolated thrombocytopenia (key finding).

Normal appearing platelets

No giant platelets on peripheral smear (if present suggest congenital thrombocytopenia.)

Normal WBC count and hemoglobin .

Coagulation studies are normal

Bleeding time is may be prolonged .

Haemophilia A & B Deficiencies of clotting factor VIII (haemophilia A) or factor IX

(haemophilia B or Christmas disease)

First day of life –rare

Severe bleeding usually occurs at, for example, circumcision or when mobility increases.

Both disorders of coagulation affect 1 in 10 000 of the population.

They are X linked and clinically indistinguishable.

The diagnosis may be suspected from the family history and can be confirmed antenatally.

Hemarthrosis

Purpuric Rashes Sepis (very sick)

Enteroviral infections (well)

Leukaemia

Henoch-Scholein Purpura

Child Abuse (family hx)

Trauma & Vasomotor

Straining

Investigation of Coagulopathy FBE/platelet count

Blood Film

aPTT

PT or INR

Fibrinogen

Further test requires specialist/haemotologist consult

Screening Test & Result Result Causes Low platelet -ITP -Congenital thromobocytopenic syndromes -Chemotherapy -Marrow replacement Isolated prolonged aPTT -Factor XI, IX, VIII deficiency Heparin, vWF deficiency Isolated/prolonged PT/INR Factor VII deficiency , Warfarin Prolonged PT, aPTT Vitamin K deficiency Low fibrinogen Liver ds, DIC (also low PLT)

If above screening tests are normal consider Factor XIII deficiency

vWF deficiency

Platelet function defect

Capillary fragility syndrome

If still in doubt –trial of FFP+/- platelet

General measures Analgesic: avoid spirin

Splint joints to relieve pain

Avoid IM injections

Avoid arterial punctures

Consult with haematologist/Specialist consultant if Haemophilia A/B

Neonatal Jaundice

Markedly elevated Unconjugated Bil –risk of damage to cells of basal ganglia and brainstem.

Excess unconj Bilirubin release and decreased capacity of liver to conjugate

Jaundice obvious at 80umol/l

White child ---skin is visible to the naked eye

Black child- sclerae should be examined as jaundice is more difficult to recognise.

Jaundice first appears in the face and spreads to the periphery of the limbs

The level is more than 270umol/l if the hands or feet are jaundiced.

Spread of jaundice in the skin.

Causes of jaundice Cause Onset

Red cell incompatibility Within 24 hours of birth

Physiological jaundice After 24 hours

Septicaemia Usually after fourth day

Common causes hepatic immaturity, /physiological

is common both in preterm and in full term babies.

Temporary deficiency of glucuronyl transferase enzymes

Full Term bab y : jaundice always appears after the first 24 hours of life and

reaches a peak on the fourth or fifth day.

In preterm infants: usually begins 48 hours after birth and may last up to two weeks.

Red cell incompatibility,

jaundice appears within 24 hours of birth.

Causes are;

(a) incompatible Rhesus grouping,

and (b) incompatible ABO grouping; the mother’s blood is usually group O and the infant’s group A or, less commonly, group B.

infective causes Septicaemia (jaundice after day 4/unwell child)

UTI .

Breast milk jaundice Breastfed neonate /infant

About 2.5% of infants who are breastfed the serum bilirubin rises to levels between 260 and 360umol/l

Occurs 2nd /3rd week of life.

Asymptomatic and appears well

level remains constant for 3 or 4 weeks if continued BF & then fall to normal levels at 4–16 weeks.

Abnormal progesterone has been shown in the milk of some of the mothers.

Rare causes

Hypothyroidism (TSH/FT4)

Galactosaemia, (+ve reducing substances but –ve glucose test)

G6PD deficiency (early jaundice or prolonged)

Viral hepatitis (IU infection, dark, pale stool, conj hyperbil

Atresia of the bile ducts (dark /pale stool, conj hyperbil)

Usually last more than 10 days.

Indications for phototherapy and exchange transfusion.

Treatment Symptomatic –prevent kernicterus

Feeding

Hydration

Phototherapy (isomerisation)

Exchange transfusion

Phenobarb (enzyme induction)

Identify and treat specific cause

Complication of Phototherapy Dermatitis

Dehydration

Diarrhoea

Leukaemia

Acute lymphoblastic leukaemia (ALL)

most common in the age range 2-10 years, with a peak at 3-4 years.

Incidence decreases with increasing age, though there is a secondary rise after 40 years.

In children it is the most common malignant disease and accounts for 85% of childhood leukaemia.

Cause? ALL: The bcr gene is found on chromosome 22 and abl

gene on 9.

This is known as the Philadelphia chromosome (named because it was discovered at hospital in Philadelphia).

The Philadelphia chromosome is found in 25% of ALL patients (not AML). -poor prognosis

Presentation symptoms and signs ------commonly result from

BM failure or, less commonly, organ infiltration.

Anaemia (pallor, lethargy, and dyspnoea)

Neutropenia (bacterial infections of

the mouth, throat, skin, chest or perianal region.

Thrombocytopenia (spontaneous bruising, menorrhagia, bleeding from venepuncture sites, gingival bleeding, or prolonged nose bleeds)

Bone pain (organ infiltration)

Superficial lymphadenopathy,

Abdominal distension (abdominal lymphadenopathy and hepatosplenomegaly)

Respiratory distress (large mediastinal mass)

Testicular enlargement,

Meningeal syndrome.

Investigations FBE/FBC – Anaemia (normochromic, normocytic)

WBC count- 10 000 to 20000 g/L

Neutropenia

Presence of blast cells

Thrombocytopenia

Biochemical screening is particularly important if the leucocyte

count is very high, when there may be evidence of renal impairment & hyperuricaemia

Chest X-ray: mediastinal mass (+ve 70% of patients)

Bone X-rays. -lytic bone lesions

BM Aspiration with or without trephination is

hypercellular, with a predominance of immature (blast) cells.

Immunophenotyping of the antigens present on blasts isolated (myeloid vs lymphoid origin)

Cytogenetics and molecular studies often detect abnormalities, prognostic information

e.g,. Philadelphia chromosome (translocation 9 & 22) carries very poor prognosis

Atraumatic LP with cerebrospinal fluid

neurological symptoms - detect leukaemic cells in the cerebrospinal fluid, indicating involvement of the central nervous system.

Prognosis.

Higher Risk Group

Age: <1 year & >10 year old.

WBC: High count

Boys > girls

Organ Spread: CSF/testicles)

T-cell or mature B-cell (Burkitt) leukemia

Better prognosis with increased number of chromosomes (called hyperdiploidy).

“Philadelphia” chromosome or translocation between 1 and 19, or 4 and 11 have a less favorable prognosis.

Response to therapy: Children whose leukemia responds completely to therapy within 7 or 14 days of chemotherapy have a better outlook.

Management Specialist/Specialist Centres

Supportive Care

Transfusion

Platelet/FFP/cryoprecipitate

Antibiotics

Chemotherapy INDUCTION

Consolidation/Maintenance

3/more drugs

Monitor and manage Complications Immediate/long term problems

References Paediatric Handbook, RCH, Melbourne 7th Ed

Emedicine.medscape.com

ABC of clinical Haematology BMJ 2nd Ed, 2003