In autoimmune haemolytic anaemia (AIHA) due to cold agglutinin disease, the IgM antibodies cause haemolysis primarily through which mechanism?

• A Direct IgM-mediated Fc receptor phagocytosis in the spleen
• B ADCC mediated by NK cells recognising IgM-coated red cells
• C Osmotic lysis following IgM-induced red cell membrane rigidity
• D Complement activation (C3b opsonisation → extravascular in liver; terminal MAC → intravascular) ✓

Explanation

Cold agglutinin IgM antibodies bind red cell I/i antigens at peripheral cold temperatures and activate complement to C3b; C3b-coated cells undergo extravascular haemolysis predominantly in the liver (which has C3b receptors). In severe cases, MAC formation causes intravascular haemolysis. Splenic Fc-mediated phagocytosis is the dominant mechanism in warm AIHA (IgG-mediated), not cold AIHA.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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