title: Heparin-induced thrombocytopenia: molecular pathogenesis.
abstract: Heparin-induced thrombocytopenia (HIT) is a common and often serious complication of heparin therapy [1,2]. Although the reduction in platelet levels associated with HIT is usually not severe, about 10% of patients experience arterial and/or venous thromboses (HITT), which can be incapacitating or fatal [3]. Recent work done in our laboratory [4] and by others [5-7] has shown that patients with HIT/T* almost invariably have antibodies specific for complexes consisting of heparin and platelet factor 4 (PF4), a heparin-binding protein found normally in platelet alpha granules. We [4] and others [8] have developed hypotheses to explain how these antibodies cause HIT/T in patients given heparin, but knowledge of the disease process is far from complete. An unusual feature of HIT/T is that antibodies important in pathogenesis are specific for complexes made up of two normal body constituents: PF4 and heparin. These antibodies are produced by a high percentage of certain patient populations treated with heparin, but only a minority of antibody formers are adversely affected. We postulate that a fuller understanding of the molecular basis for this immune response could lead to improved diagnosis, treatment and prevention of HIT/T and to the identification of risk factors that predispose to this complication.
authors.affiliation: Blood Research Institute, The Blood Center of Southeastern Wisconsin, Inc. Milwaukee, USA.
authors.forename: Seon Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Chao Yan
authors.initials: CY
authors.lastname: Liu
authors.forename: Gian
authors.initials: G
authors.lastname: PaoloVisentin
mesh_terms: D001323:Autoantibodies / Q000097:blood; D004198:Disease Susceptibility; D006493:Heparin / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007109:Immunity; D010978:Platelet Factor 4 / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000209:etiology / Q000276:immunology
chemical_list: D001323:Autoantibodies; D010978:Platelet Factor 4; D006493:Heparin