Fundamental concepts in the pathobiology of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is among the most common causes of d rug-related immune-mediated thrombocytopenia. It is a unique syndrome, in t hat despite the fact that thrombocytopenia is the major laboratory manifest ation of HIT, its major complication is a highly morbid (and commonly fatal ) thrombotic diathesis, known as the HIT with thrombosis syndrome (HITTS). The pathogenesis of HIT and MITTS has been recently elucidated, and involve s an immune response against epitopes within circulating heparin-platelet f actor-4 (PF4) complexes. This leads to cross-linking and activation of plat elets, increasing the risk for thromboses. Furthermore, significant immunol ogical cross-reactivity occurs between endothelial-cell bound PF4 and the H IT antibody, which may lead to endothelial damage, activation, and hyperpla sia. This complex process leads to a hypercoagulable state, which may lead to overt thromboses.