A 22-year-old woman from Gujarat has microcytic hypochromic anaemia (Hb 8.2 g/dL, MCV 62 fL). Serum iron is 12 µmol/L, TIBC 28 µmol/L (low-normal), ferritin 55 ng/mL (normal). Haemoglobin electrophoresis: HbA2 2.5%, HbF 4%, HbA 93.5%. HPLC shows a borderline HbA2. The MOST important next diagnostic test to confirm a diagnosis relevant to genetic counselling is:
- A Serum erythropoietin level
- B Osmotic fragility test
- C Alpha-globin gene deletion analysis by PCR/MLPA (for alpha-thalassaemia trait) ✓
- D Serum soluble transferrin receptor (sTfR) to distinguish IDA from thalassaemia
Explanation
This patient has a clinical and laboratory picture of alpha-thalassaemia trait (two-gene deletion, α-thal-1): microcytic hypochromic anaemia with normal/borderline HbA2 (unlike beta-thalassaemia trait where HbA2 >3.5%). Normal/high-normal HbA2 with microcytic anaemia and normal iron indices strongly suggests alpha-thalassaemia (HbA2 is often at lower end). Alpha-thalassaemia cannot be diagnosed by routine electrophoresis as HbA2 and HbF are not elevated; molecular confirmation by gap-PCR or MLPA detecting the common Asian alpha-globin gene deletions (--SEA, -α3.7, -α4.2) is required. This is critical for genetic counselling — if her partner is also alpha-thal trait, their offspring risk Hb Bart's hydrops. Osmotic fragility is for haemolytic anaemias. sTfR distinguishes IDA from ACD, not alpha-thal.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.