Davidson Simon J, Wadham Paul, Rogers Louise, Burman John F
Department of Haematology, Royal Brompton Hospital, Sydney Street, London, UK.
Blood Coagul Fibrinolysis. 2007 Jun;18(4):317-20. doi: 10.1097/MBC.0b013e32806a8249.
Heparin-induced thrombocytopenia type II is a severe complication of heparin treatment that may result in thrombosis. When thrombosis occurs it carries a 50% mortality rate. The exact pathophysiology is not fully understood but in the majority of cases it is associated with the production of heparin/platelet factor 4 antibodies. The endothelium provides a protective anticoagulant surface over which blood flows. Perturbation of the endothelial cells causes a reversal of the anticoagulant properties of the cells to that of a procoagulant surface. This is often due to release or down-regulation of the anticoagulant membrane proteins such as thrombomodulin and up-regulation of procoagulant factors such as tissue factor. We studied 10 patients in our cardiothoracic institute with clinically and laboratory-confirmed heparin-induced thrombocytopenia type II for evidence of endothelial cell damage. There was a statistically significant rise in the concentrations of von Willebrand factor (P < 0.0001) and soluble thrombomodulin (P = 0.004) when patients with heparin-induced thrombocytopenia type II were compared with healthy laboratory controls and patients having had cardiopulmonary bypass surgery (von Willebrand factor 324 versus 103 versus 108 U/dl and soluble thrombomodulin 9.5 versus 2.3 versus 1.2 ng/ml, respectively). Our findings suggest that endothelial cell damage is a major factor in the pathophysiology of heparin-induced thrombocytopenia.
Ⅱ型肝素诱导的血小板减少症是肝素治疗的一种严重并发症，可能导致血栓形成。当发生血栓形成时，其死亡率为50%。确切的病理生理学尚未完全了解，但在大多数情况下，它与肝素/血小板因子4抗体的产生有关。内皮提供了一个保护性的抗凝表面，血液在其表面流动。内皮细胞的扰动导致细胞的抗凝特性逆转，变为促凝表面。这通常是由于抗凝膜蛋白如血栓调节蛋白的释放或下调以及促凝因子如组织因子的上调。我们在心胸研究所研究了10例临床和实验室确诊的Ⅱ型肝素诱导的血小板减少症患者，以寻找内皮细胞损伤的证据。与健康实验室对照和接受过体外循环手术的患者相比，Ⅱ型肝素诱导的血小板减少症患者的血管性血友病因子（P < 0.0001）和可溶性血栓调节蛋白（P = 0.004）浓度有统计学意义的升高（血管性血友病因子分别为324与103与108 U/dl，可溶性血栓调节蛋白分别为9.5与2.3与1.2 ng/ml）。我们的研究结果表明，内皮细胞损伤是Ⅱ型肝素诱导的血小板减少症病理生理学中的一个主要因素。
