In heparin-induced thrombocytopenia (HIT), the pathogenic antibody targets which antigen on platelet-factor 4 complexes?

• A IgM against GPIb-IX (Bernard-Soulier antigen) on platelet surface
• B IgG against GPIIb/IIIa (fibrinogen receptor), causing platelet destruction
• C IgE against heparin directly, causing anaphylactic platelet activation
• D IgG against PF4-heparin complex, activating platelets via FcgammaRIIA ✓

Explanation

HIT is caused by IgG antibodies (generated within 5-14 days of heparin exposure) directed against the complex formed between platelet factor 4 (PF4) and heparin. PF4-heparin-IgG immune complexes bind platelets via FcgammaRIIA (CD32a), causing platelet activation, microthrombus formation, and paradoxical thrombocytopenia from platelet consumption. This is a Type II immunological mechanism; despite low platelet counts, the major risk is thrombosis (HITT = HIT with Thrombosis). Anti-GPIIb/IIIa antibodies cause immune thrombocytopenic purpura (ITP). Anti-GPIb-IX antibodies cause Bernard-Soulier syndrome (inherited).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.