PA15.1-3 | Megaloblastic Anaemia — Aetiology, Blood Picture & Diagnostic Framework — Summary & Reflection

REFLECT

Before you read the answer below, close your notes and write out — in a table or a flowchart — your diagnostic approach to a patient with MCV 118 fL. Starting from the smear morphology, what do you look for? What laboratory tests do you order, in what sequence? How do you tell B12 from folate deficiency? How do you tell megaloblastic from non-megaloblastic? This exercise mirrors exactly how a long-answer exam question will be marked. Spend 5 minutes building your own algorithm before moving on.

KEY TAKEAWAYS

H4 SDL2 — Core Takeaways

1. Two types of macrocytosis:
• Megaloblastic = impaired DNA synthesis → macro-ovalocytes + hypersegmented neutrophils (B12, folate, drugs, inborn errors)
• Non-megaloblastic = membrane or other causes → round macrocytes, NO hypersegmented neutrophils (alcohol, liver, hypothyroid, reticulocytosis, MDS)

2. Causes of megaloblastic anaemia:
• B12 deficiency: inadequate intake (vegetarians), pernicious anaemia, terminal ileal disease
• Folate deficiency: poor diet, pregnancy, malabsorption, anticonvulsants
• Drugs: MTX (DHFR inhibitor), hydroxyurea, phenytoin
• Inborn errors (rare)

3. Blood picture signature:
• MCV often >110–130 fL
• Macro-ovalocytes + hypersegmented neutrophils (≥1 neutrophil with ≥5 lobes = pathognomonic)
• Pancytopenia in severe cases
• Raised LDH + indirect bilirubin + LOW reticulocytes = ineffective erythropoiesis

4. Marrow:
• Megaloblasts (N:C asynchrony) + giant metamyelocytes

5. B12 vs folate differentiation:
• MMA raised only in B12 deficiency
• Homocysteine raised in both
• RBC folate best marker for folate status

6. The cardinal danger: Never treat presumed folate deficiency without excluding B12 — neurological damage (SACD) progresses even as Hb recovers.