Heparin-induced thrombocytopenia: molecular pathogenesis.
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.
Lee
Seon Ho
SH
Blood Research Institute, The Blood Center of Southeastern Wisconsin, Inc. Milwaukee, USA.
Liu
Chao Yan
CY
PaoloVisentin
Gian
G
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
D001323:Autoantibodies; D010978:Platelet Factor 4; D006493:Heparin