Wittkowsky Ann K
Department of Pharmacy, University of Washington Medical Center, Seattle 98195, USA.
Pharmacotherapy. 2002 Jun;22(6 Pt 2):97S-104S. doi: 10.1592/phco.22.10.97s.33614.
Acute coronary syndromes encompass a spectrum of conditions, including myocardial infarction and unstable angina. These syndromes are related to the formation and disruption of atherosclerotic plaque. Rupture of plaque leads to thrombin generation, fibrin deposition, and platelet aggregation, ultimately resulting in restriction of blood flow and ischemia of cardiac tissue. Percutaneous coronary intervention (PCI), including angioplasty and coronary stent placement, has been developed to open occluded arteries. The frequency with which these procedures are performed speaks to their largely successful outcomes. However, the mechanical manipulations of PCI result in additional plaque rupture and damage to the vessel wall, exposing subendothelial components to blood and resulting in the initiation of the clotting cascade and in platelet activation. Left unchecked, these intertwined processes lead to formation of arterial thrombi at the site of endothelial damage, and potentially to abrupt vessel closure or embolization of thrombi into the distal microcirculation. Thrombin plays a central role in thrombus formation and platelet activation, and its inhibition significantly reduces thrombus-related sequelae. Current antithrombotic strategies during PCI are based on the traditional indirect thrombin inhibitor heparin. Heparin has several limitations in efficacy and safety, due in part to its indirect mechanism of action. Bivalirudin, a direct thrombin inhibitor, offers significant improvement over heparin in the clinical outcomes and risks associated with PCI.
急性冠状动脉综合征包括一系列病症，包括心肌梗死和不稳定型心绞痛。这些综合征与动脉粥样硬化斑块的形成和破裂有关。斑块破裂导致凝血酶生成、纤维蛋白沉积和血小板聚集，最终导致血流受限和心脏组织缺血。经皮冠状动脉介入治疗（PCI），包括血管成形术和冠状动脉支架置入术，已被开发用于开通闭塞的动脉。这些手术的执行频率表明了它们在很大程度上取得了成功。然而，PCI的机械操作会导致额外的斑块破裂和血管壁损伤，使内皮下成分暴露于血液中，从而引发凝血级联反应和血小板激活。如果不加以控制，这些相互交织的过程会在内皮损伤部位形成动脉血栓，并可能导致血管突然闭塞或血栓栓塞到远端微循环。凝血酶在血栓形成和血小板激活中起核心作用，抑制凝血酶可显著减少与血栓相关的后遗症。目前PCI期间的抗血栓策略基于传统的间接凝血酶抑制剂肝素。肝素在疗效和安全性方面有几个局限性，部分原因是其间接作用机制。比伐卢定，一种直接凝血酶抑制剂，在与PCI相关的临床结果和风险方面比肝素提供了显著改善。
