Heparin-induced thrombocytopenia (HIT) is paradoxically associated with thrombosis despite thrombocytopenia. The pathophysiology involves:

• A IgG antibodies against PF4-heparin complexes activating FcgammaRIIA on platelets causing massive platelet activation and thrombin generation ✓
• B Complement-mediated lysis of platelets via C5b-9 MAC
• C Direct platelet aggregation caused by heparin binding to GPIb
• D Anti-platelet antibodies cross-reacting with endothelial von Willebrand factor

Explanation

HIT type II is an immune-mediated disorder. Heparin binds platelet factor 4 (PF4) released from platelet alpha-granules, forming heparin-PF4 complexes that are highly immunogenic. IgG antibodies (HIT antibodies) form against these complexes; the Fab portion binds PF4-heparin while the Fc portion engages FcgammaRIIA receptors on platelets and monocytes, causing platelet activation, aggregation, and granule release — generating thrombin in a massive amplification loop. Despite thrombocytopenia (platelet consumption), the net result is a hypercoagulable state with venous and arterial thrombosis (4T's syndrome).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.