A 28-year-old woman with haemolytic anaemia, splenomegaly, and pigment gallstones has a direct Coombs test (DAT) negative result. Peripheral smear shows spherocytes. Osmotic fragility test is markedly increased. The MOST likely diagnosis and its inheritance pattern is:
- A Warm autoimmune haemolytic anaemia; acquired (not inherited)
- B Hereditary spherocytosis (HS); autosomal dominant in 75% of cases (spectrin/ankyrin defect) ✓
- C G6PD deficiency; X-linked recessive; triggered by oxidant stress
- D Cold agglutinin disease; IgM-mediated, associated with Mycoplasma infection
Explanation
Hereditary spherocytosis is the most common hereditary haemolytic anaemia in Northern Europeans. It is caused by defects in red cell membrane proteins (spectrin, ankyrin, band 3, protein 4.2), causing loss of membrane and spherocyte formation. DAT is negative (distinguishing it from AIHA). Increased osmotic fragility (EMA binding test on flow cytometry is the modern gold standard) confirms the diagnosis. Inheritance is autosomal dominant in ~75% of cases. G6PD shows bite cells/Heinz bodies, not spherocytes. Cold agglutinin disease has a positive DAT (IgM complement-mediated).
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.