title: Pathogenesis of heparin-induced thrombocytopenia and thrombosis.
abstract: Heparin-induced thrombocytopenia and thrombosis (HIT/T) is a common immune-mediated disorder often manifested by life-threatening thrombosis. There is increasing evidence to indicate that HIT/T is caused by antibodies to complexes between platelet factor 4 (PF4) and heparin that activate platelets, monocytes and vascular endothelium leading to the generation of thrombin. Advances in defining the immunological basis of HIT/T have yielded insights into the antigenic determinants, antibody-antigen interactions and effector responses that contribute to its pathogenesis. However, these studies also reveal that anti-PF4/heparin antibodies develop far more commonly than clinically overt disease, raising questions as to serologic and other factors that predispose to clinical thrombocytopenia and thrombosis. An improved understanding of the natural history of HIT/T and the introduction of alternative anticoagulants have led to a somewhat improved clinical outcome. The recent development of a monoclonal anti-heparin/PF4 antibody and the establishment of a murine model of HIT/T may help to better define the pathogenesis and management of this common autoimmune disorder.
authors.affiliation: Division of Hematology, Duke University Medical Center, Box 3486, Durham, NC 27710, USA. arepa001@mc.duke.edu
authors.forename: Gowthami
authors.initials: G
authors.lastname: Arepally
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Cines
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D015551:Autoimmunity / Q000276:immunology; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D015539:Platelet Activation / Q000276:immunology; D010978:Platelet Factor 4 / Q000276:immunology; D013921:Thrombocytopenia / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D013927:Thrombosis / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology / Q000473:pathology
chemical_list: D000925:Anticoagulants; D010978:Platelet Factor 4; D006493:Heparin