Fundamental concepts in the pathobiology of heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is among the most common causes of drug-related immune-mediated thrombocytopenia. It is a unique syndrome, in that despite the fact that thrombocyto-penia is the major laboratory manifestation 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 HITTS has been recently elucidated, and involves an immune response against epitopes within circulating heparin-platelet factor-4 (PF4) complexes. This leads to cross-linking and activation of platelets, increasing the risk for thromboses. Furthermore, significant immunological cross-reactivity occurs between endothelial-cell bound PF4 and the HIT antibody, which may lead to endothelial damage, activation, and hyperplasia. This complex process leads to a hypercoagulable state, which may lead to overt thromboses.
Januzzi
J L
JL
Cardiology Division and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Jang
I K
IK
D000925:Anticoagulants / Q000009:adverse effects*; D002634:Chemotaxis, Leukocyte; D003429:Cross Reactions; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D000939:Epitopes; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D007111:Immunity, Cellular; D007249:Inflammation; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D010978:Platelet Factor 4 / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology*; D019851:Thrombophilia / Q000209:etiology; D013927:Thrombosis / Q000209:etiology
D000925:Anticoagulants; D000939:Epitopes; D010978:Platelet Factor 4; D006493:Heparin