Becker R
Cardiovascular Thrombosis Research Center, Division of Cardiovascular Medicine, University of Massachusetts Medical Center, Worcester, Massachusetts 01655-0214, USA.
Clin Cardiol. 1997 Nov;20(11 Suppl 3):III2-5. doi: 10.1002/clc.4960201403.
The dynamics of coronary thrombosis and reocclusion may seem straightforward, but in actuality they are complex and incompletely understood. The pathobiology of coronary thrombosis begins with the development of the atherosclerotic plaque. The initial step in the process, endothelial cell dysfunction, alters vascular thromboresistance. Plaque erosion or overt disruption is followed by platelet adherence, aggregation, and thrombin generation that stimulates the conversion of soluble fibrinogen to fibrin. Thrombolytic therapy, although able to dissolve a high proportion of occlusive thrombi, creates a procoagulant environment by generating plasmin which, in turn, activates platelets and generates thrombin, increasing the likelihood of vessel reocclusion. Thrombin is therefore considered an important target for research, and several thrombin inhibitors have been developed. Antiplatelet agents such as aspirin are currently employed to prevent reocclusion following thrombolytic therapy; however, several new and more potent platelet antagonists are being investigated with considerable enthusiasm.
冠状动脉血栓形成和再闭塞的动态过程看似简单直接，但实际上却很复杂，尚未完全被理解。冠状动脉血栓形成的病理生物学始于动脉粥样硬化斑块的形成。该过程的第一步，即内皮细胞功能障碍，会改变血管的抗血栓形成能力。斑块侵蚀或明显破裂之后会出现血小板黏附、聚集以及凝血酶生成，凝血酶会刺激可溶性纤维蛋白原转化为纤维蛋白。溶栓治疗虽然能够溶解很大比例的闭塞性血栓，但会通过生成纤溶酶而营造一种促凝环境，纤溶酶反过来又会激活血小板并生成凝血酶，从而增加血管再闭塞的可能性。因此，凝血酶被视为一个重要的研究靶点，并且已经研发出了几种凝血酶抑制剂。目前使用阿司匹林等抗血小板药物来预防溶栓治疗后的再闭塞；然而，几种更新且更有效的血小板拮抗剂正受到相当热烈的研究。
