A 28-year-old woman develops severe thrombocytopenia 5 days after initiating unfractionated heparin therapy for deep vein thrombosis. Her platelet count falls from 210,000 to 42,000/μL. She develops a new arterial thrombus in the left popliteal artery. The 4T score pre-test probability is high. The pathomechanism of heparin-induced thrombocytopenia type II (HIT) is:

• A Direct heparin-mediated platelet membrane lysis via complement activation on platelet surfaces
• B IgG antibodies against the PF4-heparin complex bind FcgammaRIIA on platelets, causing Fc receptor-mediated platelet activation, aggregation, and consumption alongside endothelial injury and thrombin generation ✓
• C Heparin cross-linking of GPIb-IX-V receptors causing spontaneous platelet aggregation independent of antibody formation
• D ADAMTS13 inhibition by heparin-anti-PF4 complexes causing vWF multimer accumulation and platelet consumption

Explanation

HIT type II is an immune-mediated disorder where heparin binds to platelet factor 4 (PF4) released from activated platelets, forming PF4-heparin complexes that act as neoantigens. IgG antibodies generated against PF4-heparin complexes bind these complexes on platelet surfaces and engage FcgammaRIIA (CD32) receptors, causing Fc receptor-mediated platelet activation, degranulation, and generation of procoagulant platelet microparticles. Simultaneously, PF4-heparin complexes on endothelial surfaces activate endothelial cells via FcgammaRIIa, inducing tissue factor expression and thrombin generation — producing a paradoxical prothrombotic state with thrombocytopenia (HITT: HIT with thrombosis). Management requires immediate heparin cessation and substitution with a non-heparin anticoagulant (argatroban, bivalirudin, fondaparinux). ADAMTS13 is the relevant enzyme in TTP, not HIT.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.