Pathogenesis of heparin-induced thrombocytopenia and thrombosis.
Pathogenesis of heparin-induced thrombocytopenia and thrombosis.
复制标题
DOI：
10.1016/s1568-9972(02)00031-9
复制
发表时间：
2002-05-01
影响因子：
13.6
通讯作者：
Cines, Douglas B.
中科院分区：
文献类型：
--
作者：
Arepally, Gowthami;Cines, Douglas B.
肝素诱导的血小板减少和血栓形成(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是由抗血小板第4因子(PF4)和肝素复合物的抗体引起的，它激活了血小板、单核细胞和血管内皮细胞，导致凝血酶的产生。在确定HIT/T的免疫学基础方面取得了进展，对其发病机制中的抗原决定簇、抗体-抗原相互作用和效应反应有了深入的了解。然而，这些研究也表明，抗PF4/肝素抗体比临床上常见的疾病更常见，这就提出了血清学和其他易导致临床血小板减少和血栓形成的因素的问题。对HIT/T自然病史的更好理解和替代抗凝剂的引入在一定程度上改善了临床结果。最近研制的抗肝素/PF4单抗和HIT/T小鼠模型的建立可能有助于更好地确定这种常见的自身免疫性疾病的发病机制和治疗。
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.