Pathogenesis and management of heparin-induced thrombocytopenia and thrombosis

Heparin-induced thrombocytopenia and thrombosis is a severe immune-mediated adverse drug effect caused by the IgG antibodies to platelet factor4/heparin complexes. Activated platelets, vascular endothelium, and monocytes generate the life-threatening thrombocytopenia and thrombosis. In this review, we will update the reader on recent findings on the pathogenesis and clinical management of heparin-induced thrombocytopenia and thrombosis. Firstly, PF4/heparin complexes make IgM mediate complement activation by classical pathway. Secondly, Marginal zoneB cells play a crucial role in producing anti-PF4/heparin complex IgG antibody. Thirdly, two activation signals of platelets (protease-activated receptor 1/Fc gamma IIA receptor) were confirmed. Based on these findings, we present a potential laboratory test of HITT (receptor glycoprotein IV) and two possible treatments by using receptor inhibitors (vorapaxar/atopaxar) and IgG-degrading enzyme (streptococcus pyogenes/glutamyl endopeptidase V8/matrix metalloproteinases).