Heparin-induced thrombocytopaenia (HIT) is a serious immune complication. The pathophysiology involves antibodies against which antigen complex, and the resulting paradoxical risk is:

• A Antibodies against heparin-antithrombin III complexes causing antithrombin depletion and loss of anticoagulation
• B IgG antibodies against heparin-platelet factor 4 (PF4) complexes that activate platelets via FcgammaRIIA receptors, causing paradoxical THROMBOSIS despite thrombocytopaenia ✓
• C IgM antibodies against heparin-thrombin complexes consuming coagulation factors and causing bleeding
• D Complement-mediated lysis of platelets after heparin binds to GpIIb/IIIa receptors

Explanation

In HIT, UFH (or LMWH less commonly) binds to platelet factor 4 (PF4) released from activated platelets, forming PF4-heparin complexes that are highly immunogenic. IgG antibodies against PF4-heparin complexes bind to FcgammaRIIA receptors on platelets, causing platelet activation, aggregation and thrombocytopenia from platelet consumption. This paradoxically creates a hypercoagulable state with venous and arterial thrombosis (HITT — HIT with thrombosis). Heparin must be immediately discontinued and a non-heparin anticoagulant (e.g., argatroban, fondaparinux, bivalirudin) substituted. Warfarin must not be started until platelet count has recovered to reduce risk of limb gangrene.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.