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Paediatric Hematology - Exam Revision Notes

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1. ANAEMIAS IN CHILDREN

Overview of Causes

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Iron Deficiency Anaemia (IDA)

• Most common anaemia in children
• Peak risk: infants/toddlers (1-3 years), teens (especially girls)
• Causes in children:
  • Exclusive breastfeeding without iron supplementation (after 4-6 months)
  • Excessive cow's milk before age 1 year (displaces iron-rich foods + causes low-grade GI bleeding)
  • Milk protein colitis causing occult GI bleeding
  • Nutritional IDA uncommon after age 3-4 years -- if present, suspect occult bleeding
• Clinical features: pallor, fatigue, pica (craving for ice, dirt, paper), irritability
• Labs:
  • Hypochromic microcytic anaemia
  • Low reticulocyte count
  • Low serum ferritin, low serum iron, high TIBC
• Treatment:
  • Oral ferrous sulfate (outpatient if hemodynamically stable)
  • Severe anaemia/hemodynamic compromise: inpatient + hematology consult ± transfusion
• Prevention (AAP): iron supplementation in breastfed infants, iron-fortified formulas, delay cow's milk until >1 year, universal Hb screening at 1 year

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Autoimmune Hemolytic Anaemia (AIHA)

• Mechanism: autoantibodies against RBC antigens → destruction
• Primary AIHA: most common in infants/young children, often post-viral, no underlying disorder
• Secondary AIHA: older children -- associated with malignancy, HIV, autoimmune disease
• Labs:
  • Spherocytes + schistocytes on peripheral smear
  • Elevated indirect bilirubin, elevated LDH, urobilinogenuria/hemoglobinuria
  • Elevated reticulocytes (unless acute, sudden onset)
  • Positive Coombs test (direct antiglobulin test)
• Management: steroids, IVIG, avoid precipitants

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Transient Erythroblastopenia of Childhood (TEC)

• Self-resolving normocytic anaemia from temporary ↓ RBC precursors
• Age: 6 months to 10 years (peak: toddlers/preschool)
• Other cell lines normal, iron studies normal
• Recovery in 1-2 months; transfusion rarely needed
• Must differentiate from Diamond-Blackfan anaemia

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Parvovirus B19 & Aplastic Crisis

• Parvovirus replicates in erythroid progenitor cells → transient red cell aplasia
• In normal host: "fifth disease" (slapped cheek rash) -- anaemia not noticed
• In children with haemoglobinopathy/haemolytic anaemia (SCD, thalassaemia): severe aplastic crisis, often requires transfusion

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2. HAEMOGLOBINOPATHIES

Sickle Cell Disease (SCD)

• Genetics: autosomal recessive; HbS due to Glu→Val substitution at position 6 of β-globin chain
• HbSS = sickle cell disease (most severe); HbAS = sickle cell trait (carrier, usually asymptomatic)
• Pathophysiology: HbS polymerises under low O₂ → sickling → vaso-occlusion, haemolysis

• Hydroxyurea (↑ HbF, reduces crises)
• Penicillin prophylaxis from age 2 months to 5 years
• Pneumococcal vaccination
• Folic acid supplementation
• Transfusion for acute chest syndrome, stroke, aplastic crisis, pre-op
• Curative: bone marrow transplant
• Gene therapy (approved 2023-24): exagamglogene autotemcel (exa-cel) for age ≥12 years with recurrent vaso-occlusive crises - Harrison's 22e

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Thalassaemia

• α-globin: 2 genes on each chromosome 16 (total 4 alleles)
• β-globin: 1 gene on chromosome 11 (2 alleles)
• α-thalassaemia: mainly gene deletions
• β-thalassaemia: mainly point mutations affecting transcription, splicing, or translation of β-globin mRNA

1. ↓ β-globin → ↓ HbA formation → microcytic hypochromic RBCs
2. Excess unpaired α-chains → toxic precipitates → membrane damage → ineffective erythropoiesis + shortened RBC lifespan
3. Ineffective erythropoiesis → massive erythroid hyperplasia → extramedullary haematopoiesis
4. Bone marrow expansion → skeletal deformities (frontal bossing, "hair-on-end" skull XR, "chipmunk facies")
5. Hepcidin suppressed → increased iron absorption → iron overload (even without transfusions)

• Presents postnatally as HbF declines (by 6 months)
• Growth retardation from infancy
• Hepatosplenomegaly (extramedullary haematopoiesis + haemolysis)
• Facial deformities (bone marrow expansion)
• Iron overload → cardiomyopathy, liver cirrhosis, endocrinopathies (most common cause of death = cardiac failure)

• β-Thal major: marked microcytosis, hypochromia, poikilocytosis, anisocytosis, nucleated RBCs (normoblasts), target cells
• β-Thal minor/α-thal trait: mild microcytosis, hypochromia, target cells -- similar to IDA

• Regular blood transfusions (every 3-4 weeks, target Hb 9-10 g/dL)
• Iron chelation: desferrioxamine (IV/SC), deferasirox (oral)
• Curative: allogeneic bone marrow transplant
• Splenectomy if hypersplenism causing excessive transfusion requirement

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3. BLEEDING DISORDERS

Immune Thrombocytopenia (ITP)

• Previously called "idiopathic thrombocytopenic purpura"
• Mechanism: autoantibodies (anti-platelet IgG) against platelet membrane glycoproteins → platelet destruction + sometimes ↓ megakaryocyte production
• Epidemiology:
  • Typical patient: preschool/school-age, previously healthy child
  • Onset: acute, often follows viral illness
  • >80% of childhood ITP is self-limited (resolves within 6 months)
  • Incidence of life-threatening bleeds <0.5%
• Classification:
  • Acute: resolves <3 months
  • Persistent: 3-12 months
  • Chronic: >12 months

• Acute onset petechiae + bruising
• No lymphadenopathy, no hepatosplenomegaly, no fever (if present, think OTHER diagnosis)
• Labs: isolated thrombocytopenia (WBC and Hb normal)

• Observation alone if mild/no bleeding
• Corticosteroids: prednisone 2 mg/kg/d × 21 days OR methylprednisolone 30 mg/kg/d × 4 days
  • Caution: must rule out leukemia/aplastic anaemia before starting steroids (bone marrow biopsy if uncertain)
• IVIG: 1 g/kg/d -- superior to steroids for rapid platelet increment
• Anti-Rh(D) immunoglobulin (WinRho): only for Rh-positive patients; 50-75 µg/kg; risk of intravascular haemolysis (needs admission)
• Life-threatening haemorrhage: single-donor platelets (2-3x normal dose) + IV methylprednisolone + IVIG

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Haemophilia

• Often discovered early: family history, intracranial haemorrhage at birth, hematoma after birth trauma, prolonged bleeding after circumcision, or first fall as toddler
• Screening: prolonged aPTT; normal PT, platelet count, bleeding time
• Confirmation: quantitative factor VIII or IX levels
• Mixing studies to detect inhibitors

• "When in doubt, treat" - preferably within 2 hours
• Factor replacement:
  • 1 unit/kg of Factor VIII raises activity by 2%
  • 1 unit/kg of Factor IX raises activity by 1%
  • Target level: 40-50% for routine bleeds; 80-100% for CNS, retroperitoneal, iliopsoas, GI, ophthalmic bleeds
• DDAVP (desmopressin): releases endogenous Factor VIII + vWF; useful in mild/moderate haemophilia A and carriers
• Prophylactic Factor infusions (especially in severe disease) - prevent hemophilic arthropathy
• Adjuncts: tranexamic acid / aminocaproic acid (antifibrinolytics) for mucosal/dental bleeds; RICE (rest, ice, compression, elevation) for joints
• Inhibitors (antibodies to factor): 30% of severe haemophilia A; treat with FEIBA® (activated PCC) or recombinant Factor VIIa (NovoSeven®)

• Haemophilic arthropathy (repeated haemarthroses → synovial inflammation → cartilage destruction → joint fibrosis)
• Iliopsoas bleed: mimics appendicitis; hip held in flexion, femoral nerve compression
• Leading cause of death: intracranial haemorrhage

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Von Willebrand Disease (vWD)

• Most common inherited bleeding disorder overall
• vWF deficiency/dysfunction → impaired platelet adhesion to subendothelium + ↓ Factor VIII stability
• Types: Type 1 (mild, quantitative ↓), Type 2 (qualitative defect), Type 3 (severe, absent vWF)
• Labs: prolonged bleeding time, prolonged aPTT (if Factor VIII very low), normal PT, low vWF antigen/activity
• Treatment: DDAVP (Type 1), vWF concentrate, tranexamic acid

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4. PAEDIATRIC LEUKAEMIA

Acute Lymphoblastic Leukaemia (ALL)

• Most common childhood malignancy (most common childhood leukaemia)
• Peak incidence: 2-10 years of age
• B-ALL = most common subtype

• Mutations in transcription factors regulating lymphoid differentiation (e.g., PAX5 in B-ALL)
• Driver mutations: tyrosine kinases, RAS signalling, chromatin regulators
• Philadelphia chromosome (t(9;22) BCR-ABL): ~5% of childhood ALL, ~25% of adult ALL - worst prognosis historically; now targetable with tyrosine kinase inhibitors (imatinib)

• Anaemia: pallor, fatigue, weakness
• Thrombocytopenia: petechiae, bruising, mucosal bleeding
• Neutropenia: recurrent/severe infections
• Bone/joint pain (marrow infiltration)
• Lymphadenopathy, hepatosplenomegaly
• T-ALL: mediastinal mass (>50% of T-ALL cases) -- thymic involvement

• Peripheral blood: blasts (lymphoblasts); pancytopenia
• Elevated WBC or normal/low WBC with blasts
• LDH elevated

• Induction (remission) → Consolidation → Maintenance (total 2-3 years)
• CNS prophylaxis (IT methotrexate ± cranial irradiation in high risk)
• Prognosis: >90% cure rate in standard-risk childhood B-ALL

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Acute Myeloid Leukaemia (AML) in Children

• Less common than ALL in children; more common in adults
• May arise de novo or from prior myelodysplastic syndrome
• Acute promyelocytic leukaemia (APL, AML-M3):
  • t(15;17) → PML-RARA fusion → block in promyelocyte differentiation
  • Risk of DIC (thromboplastic granule release)
  • Treatment: All-trans retinoic acid (ATRA) + arsenic trioxide -- bypass the differentiation block

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5. NEUTROPENIA IN CHILDREN

• Infants/African/Middle Eastern descent: ANC can be lower, but should not drop <1000/mm³

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6. HIGH-YIELD EXAM COMPARISONS

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7. KEY MNEMONICS & HIGH-YIELD POINTS

• "5's" in haemophilia: 5% = mild; bleeding only with trauma
• Haemarthroses = hallmark of haemophilia (80% of bleeds in severe)
• Leading cause of death in haemophilia = intracranial haemorrhage
• ITP in children: >80% self-limited - don't over-treat
• Sickle cell + fever = emergency (functional asplenia → sepsis)
• Dactylitis = first presentation of SCD in infants
• β-Thalassaemia major: "hair-on-end" skull XR, chipmunk facies, iron overload kills (cardiac failure)
• B-ALL peak: age 2-10 years; T-ALL: adolescent boys + mediastinal mass
• Parvovirus B19 = aplastic crisis in SCD/thalassaemia
• Philadelphia chromosome (BCR-ABL): present in CML and ~5% childhood ALL; treated with TKIs

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