Arepally Gowthami, Cines Douglas B
Division of Hematology, Duke University Medical Center, Box 3486, Durham, NC 27710, USA.
Autoimmun Rev. 2002 May;1(3):125-32. doi: 10.1016/s1568-9972(02)00031-9.
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.
肝素诱导的血小板减少症和血栓形成（HIT/T）是一种常见的免疫介导性疾病，常表现为危及生命的血栓形成。越来越多的证据表明，HIT/T是由针对血小板因子4（PF4）与肝素复合物的抗体引起的，这些抗体激活血小板、单核细胞和血管内皮，导致凝血酶生成。在确定HIT/T免疫基础方面的进展，为有助于其发病机制的抗原决定簇、抗体-抗原相互作用和效应反应提供了见解。然而，这些研究也表明，抗PF4/肝素抗体的产生远比临床显性疾病更为常见，这就引发了关于易导致临床血小板减少症和血栓形成的血清学及其他因素的问题。对HIT/T自然史的进一步了解以及替代抗凝剂的引入，已使临床结果有所改善。单克隆抗肝素/PF4抗体的近期研发以及HIT/T小鼠模型的建立，可能有助于更好地界定这种常见自身免疫性疾病的发病机制和治疗方法。
