A 34-year-old woman has progressive fatigue and mild jaundice. Hemoglobin is 7.5 g/dL, reticulocytes 12%, LDH elevated, and haptoglobin undetectable. Smear shows numerous spherocytes. Direct antiglobulin test is positive for IgG and C3b. Which is the most likely diagnosis?

• A Paroxysmal cold hemoglobinuria
• B Hereditary spherocytosis
• C Cold agglutinin disease
• D Warm antibody autoimmune hemolytic anemia ✓

Explanation

IgG opsonized red cells are removed by splenic macrophages, partially phagocytosing membrane to form spherocytes, so warm AIHA mimics hereditary spherocytosis. The positive direct Coombs test with IgG and C3b separates it from HS, where Coombs is negative. Cold agglutinin disease features IgM with complement at low temperature and agglutinated rouleaux like clumps on the smear, while paroxysmal cold hemoglobinuria is caused by the Donath Landsteiner antibody and gives intravascular hemolysis.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.