In heparin-induced thrombocytopenia type 2 (HIT-2), the mechanism of platelet activation and paradoxical thrombosis involves:

• A Direct heparin-mediated platelet GPIIb/IIIa receptor blockade causing paradoxical release
• B Complement C3a-mediated platelet lysis releasing procoagulant microparticles
• C IgG antibodies against platelet factor 4 (PF4)-heparin complexes binding FcγRIIA on platelets causing activation and TXA2/ADP release ✓
• D Thrombin-mediated PAR-1 receptor activation on platelets by heparin metabolites

Explanation

HIT-2 is an immune-mediated prothrombotic disorder: heparin binds platelet factor 4 (PF4) released from platelet alpha-granules, forming PF4-heparin complexes that expose new antigenic epitopes. IgG antibodies develop against these neoepitopes; the IgG-PF4-heparin immune complexes engage FcγRIIA receptors on platelets, causing platelet activation, release of procoagulant microparticles, and thrombocytopenia. This creates a highly prothrombotic state despite low platelet count, explaining the paradoxical thrombosis in HIT.

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

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