Paediatric Aplastic Anaemia
Lesson Objectives
By the end of this lesson, learners should be able to:
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Define aplastic anaemia and recognize laboratory diagnostic criteria.
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Identify clinical features and congenital vs. acquired forms.
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List differential diagnoses for bone marrow failure.
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Outline appropriate investigations for diagnosis and severity assessment.
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Describe supportive, infection prophylactic, and definitive treatments including HSCT and immunosuppressive therapy.
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Monitor response to therapy and adjust management accordingly.
Description
Aplastic anaemia is pancytopenia resulting from bone marrow failure, with hemoglobin <10 g/dL, platelet count <50 × 10⁹/L, and granulocytes <1.5 × 10⁹/L. Bone marrow aspirate and trephine show hypocellularity without significant fibrosis or malignant infiltration.
It may be acquired due to infections, drugs, toxins, or autoimmune conditions, or inherited as part of bone marrow failure syndromes such as Fanconi anaemia or Shwachman-Diamond syndrome.
Clinical Features
| Feature | Description |
|---|---|
| Pallor | Secondary to anemia |
| Easy bruising / Spontaneous bleeding | Epistaxis, petechiae, purpura |
| Lymphadenopathy / Hepatosplenomegaly | May indicate underlying disorder or secondary infection |
| Joint swelling | Occasionally seen in autoimmune or congenital syndromes |
| Jaundice | Suggests hemolysis or liver involvement |
| Congenital features | Café au lait spots, short stature, limb/nail/digit abnormalities |
Differential Diagnosis
| Acquired | Inherited |
|---|---|
| Viral infections: Hepatitis A, B, C, CMV, HIV | Fanconi anaemia, Dyskeratosis congenita, Shwachman-Diamond syndrome |
| Medications/toxins: Benzene, chloramphenicol, cytotoxic drugs, radiation | Pancytopenia associated with primary immunodeficiency |
| Nutritional deficiencies: Zinc, copper, B12, folate | Myelodysplastic syndrome, PNH |
| Rheumatologic disorders | — |
Investigations
| Investigation | Purpose / Findings |
|---|---|
| FBC, differential, peripheral smear, reticulocyte count | Confirm pancytopenia |
| Hb electrophoresis | Rule out haemoglobinopathies |
| Bone marrow aspirate and trephine (BMAT) | Assess cellularity, exclude fibrosis/malignancy |
| Liver function tests (ALT, AST, ALP, bilirubin, albumin, GGT, INR/PTT) | Assess liver involvement |
| Electrolytes (Na, K, Cl, Ca, Mg, Phosphate) | Baseline metabolic status |
| Renal function tests (urea, creatinine) | Assess kidney function |
| DAT, haptoglobin, LDH, ESR | Evaluate hemolysis and inflammation |
| Iron studies (serum iron, ferritin, transferrin) | Assess iron status |
| Viral studies | Hepatitis A, B, C, CMV, HIV |
| Autoimmune tests | ANA, dsDNA, RF, complement (C3/C4, CH50), immunoglobulins |
| Vitamin assays | B12, serum and red cell folate |
| HLA typing | For potential stem cell transplant |
Investigations for inherited forms: Chromosomal breakage (Fanconi anaemia), flow cytometry for CD55/CD59 (PNH), SBDS gene testing (Shwachman-Diamond), telomere length (Dyskeratosis congenita), abdominal ultrasound for congenital anomalies.
Supportive Management
| Step | Action |
|---|---|
| Blood transfusion | PRBCs to maintain Hb >7 g/dL; platelets to maintain >10 × 10⁹/L (well) or >20 × 10⁹/L (febrile) |
| Fever / neutropenia | Neupogen (G-CSF) 5 mcg/kg/day SC; escalate up to 60 mcg/kg/day or 1,500 mcg/day if severe/refractory |
| Infection prevention | PJP prophylaxis: pentamidine (300 mg inhaled q4w >6 yrs; IV <6 yrs), dapsone (avoid in G6PD deficiency) |
| Fungal prophylaxis | Fluconazole 3 mg/kg/day IV/PO (max 400 mg/day); monitor interactions with cyclosporine |
Definitive Treatment
| Scenario | Treatment |
|---|---|
| Matched sibling donor available | Hematopoietic stem cell transplant (HSCT), ~90% cure rate; HLA typing required; arrange via UTH Children’s Hospital |
| No matched sibling donor | Immunosuppressive therapy (IST) with admission: baseline labs, FBC, liver/renal function, electrolytes |
| IST regimen | ATG 40 mg/kg IV daily ×4 days; prednisolone 1 mg/kg PO BID ×7 days, taper over 3 weeks; cyclosporine 5 mg/kg PO q12h, adjust to maintain trough 150–200 mcg/L |
| Pre-medications for IST | Paracetamol 15 mg/kg PO pre-ATG q6h PRN; diphenhydramine 1 mg/kg PO/IV pre-ATG q6h PRN; pethidine 1 mg/kg IM q6h PRN |
Post-IST: If no response at 3–6 months, consider unrelated donor HSCT with detailed family discussion.
Summary
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Aplastic anaemia is pancytopenia from bone marrow failure.
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Clinical signs: pallor, bleeding, bruising, jaundice, congenital anomalies.
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Investigations: FBC, bone marrow, viral studies, autoimmune tests, iron and vitamin levels, HLA typing.
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Supportive management: transfusion, infection prevention, G-CSF for neutropenia.
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Definitive therapy: HSCT if sibling donor; IST if no donor.
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Post-IST: monitor response, plan for unrelated donor transplant if necessary.