Fig. 1.
Key elements of heparin-induced thrombocytopenia (HIT)–induced severe prothrombotic state. Antibodies bind to ultralarge complexes formed by platelet factor 4 and heparin. Binding of these immunocomplexes to the platelet FcϒRIIa immunoreceptor leads to platelet activation, with platelet degranulation, further release of platelet factor 4 and platelet aggregation, with release of microparticles that enhance thrombin generation and further platelet activation. This self-amplifying cascade of platelet activation, platelet consumption, and sequestration finally results in an acute decrease of the platelet count and thrombocytopenia. Thrombin generation is further accelerated via binding of the immunocomplexes to neutrophil FcϒRIIa immunoreceptors, which induces the formation of neutrophil extracellular traps (NEtosis). Binding to the monocyte FcϒRIIa immunoreceptor leads to cell surface tissue factor expression and its release via microparticles. In addition to this immune immunoglobulin G–mediated cell activation, immunoglobulin G binds to endothelial cell–bound platelet factor 4, which further promotes tissue factor expression, thrombin generation, and thrombus formation. From Arepally GM, Padmanabhan A: Heparin-induced thrombocytopenia: A focus on thrombosis. Arterioscler Thromb Vasc Biol 2021; 41:141–52, https://www.ahajournals.org/doi/10.1161/ATVBAHA.120.315445, with permission. © 2020 American Heart Association, Inc.