Heparin-induced thrombocytopenia type II (HIT) is paradoxically associated with thrombosis rather than bleeding. The immune mechanism responsible is:

• A IgG antibodies form against platelet glycoprotein IIb/IIIa cross-linked by heparin, directly lysing platelets via complement
• B Heparin directly activates von Willebrand factor multimers, which trap platelets in microvessels causing platelet consumption
• C Heparin downregulates thrombomodulin on endothelial cells, reducing protein C activation and promoting a pro-coagulant state
• D IgG antibodies bind heparin-platelet factor 4 (PF4) complexes; these immune complexes engage FcγRIIA receptors on platelets, causing platelet activation, release reaction, thrombin generation, and thrombocytopenia simultaneously ✓

Explanation

In HIT type II, heparin forms a neoantigen complex with platelet factor 4 (PF4, a platelet-released chemokine). The immune system generates IgG antibodies against this heparin-PF4 complex. These antibodies then engage FcγRIIA receptors on platelets, causing massive platelet activation, degranulation (releasing more PF4, amplifying the reaction), thrombocytopenia from platelet consumption, and paradoxical thrombin generation leading to venous/arterial thrombosis ('white clot syndrome'). Management: immediately stop all heparin (including flushes), start a non-heparin anticoagulant (argatroban, bivalirudin, or danaparoid), and avoid platelet transfusions.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.