Heparin-induced thrombocytopaenia (HIT) is a life-threatening complication. The pathophysiological mechanism of HIT type II involves:
- A IgG antibodies against heparin-PF4 complexes that bind platelet FcgammaRIIA receptors, causing platelet activation and paradoxical thrombosis ✓
- B Direct heparin toxicity causing platelet membrane lysis via complement activation
- C Heparin-mediated competitive inhibition of thrombopoietin receptor, reducing platelet production
- D Cross-reactive antibodies against GPIb-IX-V (von Willebrand factor receptor) destroying platelets
Explanation
HIT type II is an immune-mediated disorder where heparin forms a complex with platelet factor 4 (PF4), a positively charged chemokine released from platelets. IgG antibodies recognise neo-antigenic epitopes on this heparin-PF4 complex. These antibody-antigen complexes then bind to FcgammaRIIA (Fc-gamma receptor IIA) on platelets, causing platelet activation, platelet consumption (thrombocytopaenia), and generation of prothrombotic microparticles — paradoxically resulting in a hypercoagulable state and arteriovenous thrombosis. All heparin (including low-molecular-weight heparin) must be stopped immediately and a non-heparin anticoagulant (argatroban, danaparoid, fondaparinux, or bivalirudin) substituted.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.