A patient develops thrombocytopenia 8 days after starting unfractionated heparin for DVT treatment. Platelet count dropped from 180,000 to 55,000/µL. New thrombus detected in the arm. ELISA for anti-PF4/heparin IgG is strongly positive (OD 2.4). Functional serotonin release assay (SRA) is positive. The pathogenesis of HIT Type 2 involves IgG antibodies binding PF4-heparin complexes and activating platelets through which receptor?

• A FcγRIIA (CD32) on platelet surface ✓
• B Toll-like receptor 4 (TLR4) on platelet surface
• C P2Y12 receptor (ADP receptor) activation
• D GPIb-IX-V complex on platelet surface

Explanation

In HIT Type 2, IgG antibodies directed against PF4-heparin complexes bind to PF4-heparin on the platelet surface, and the Fc portion of IgG simultaneously engages FcγRIIA (CD32), the only Fcγ receptor expressed on human platelets. FcγRIIA crosslinking activates platelet signaling via ITAM (immunoreceptor tyrosine-based activation motif) and downstream Syk kinase, leading to platelet activation, degranulation, and release of procoagulant microparticles, generating a prothrombotic state paradoxically causing thrombosis despite thrombocytopenia. FcγRIIA is also activated on monocytes, amplifying tissue factor expression.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.