A patient develops haemolysis, renal failure and thrombocytopenia after receiving a blood transfusion. The direct Coombs test (DAT) is strongly positive. This represents which hypersensitivity type and which complement pathway is primarily responsible for intravascular haemolysis?

• A Type III (immune complex) hypersensitivity; antigen-antibody complexes deposit in glomeruli and red cell membranes
• B Type I (IgE-mediated) hypersensitivity; mast cell degranulation releases vasoactive amines causing haemolysis
• C Type II (cytotoxic) hypersensitivity; IgM or IgG antibodies against donor red cell antigens activate the classical complement pathway to form MAC causing intravascular haemolysis ✓
• D Type IV (delayed-type) hypersensitivity; T-cell-mediated destruction of transfused red cells over 7–10 days

Explanation

Acute hemolytic transfusion reactions (AHTR) are the prototypic Type II (antibody-mediated cytotoxic) hypersensitivity. Pre-formed recipient IgM (most commonly anti-ABO) or IgG antibodies bind antigens on donor red cells and activate the classical complement pathway (C1q binding to Fc regions → C1r/C1s → C4b2a C3 convertase → C5b-9 MAC). IgM is particularly effective at classical pathway activation; the resulting MAC directly lyses red cells (intravascular haemolysis). IgG-mediated extravascular haemolysis via macrophage Fc receptors is a separate mechanism. Type III involves soluble immune complexes; Type IV is T-cell mediated. The positive DAT reflects antibody/complement coating of red cells.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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