A 34-year-old woman develops fatigue, dark urine, and scleral icterus two weeks after starting a new medication. Smear shows numerous spherocytes without bite cells. Direct antiglobulin (Coombs) test is strongly positive with IgG and C3. Her spleen is palpable 4 cm below costal margin. What is the predominant mechanism of red cell destruction?

• A Intravascular complement mediated lysis in the circulation
• B Mechanical fragmentation across fibrin strands in small vessels
• C Extravascular phagocytosis by splenic macrophages recognizing Fc portions of bound IgG ✓
• D Osmotic swelling and rupture due to membrane lipid loss

Explanation

Warm autoimmune hemolytic anemia is mediated by IgG, optimally active at body temperature, which opsonizes red cells. Splenic macrophages bearing Fc receptors pluck membrane from coated cells, converting them to spherocytes that are then destroyed extravasculary, hence the splenomegaly. Complement mediated intravascular lysis is characteristic of cold agglutinin disease with IgM, not warm IgG disease, so option A is the key distractor. Bite cells would suggest oxidative denaturation of hemoglobin.

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

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Written and medically reviewed by the StethoPrep medical team.