Callahan K P, Malinin A I, Gurbel P A, Alexander J H, Granger C B, Serebruany V L
Sinai Center for Thrombosis Research, Baltimore, MD 21215, USA.
Cardiology. 2001;95(2):55-60. doi: 10.1159/000047346.
Fibrinolytic therapy is the established treatment for the management of patients with ST elevation acute myocardial infarction (AMI). Present fibrinolytic regimens have a number of shortcomings, including the failure to produce early and sustained reperfusion, as well as failure to prevent reocclusion in at least some patients. Platelets play an important role in coronary thrombosis responsible for AMI. The effect of coronary fibrinolysis on platelets has been extensively debated in the literature with evidence of both platelet activation and inhibition. Among fibrinolytic agents, tissue plasminogen activator (t-PA) is considered to be the mainstay in the treatment of coronary artery disease. The native t-PA molecule has been modified in an attempt to achieve improved lytic characteristics with less risk of bleeding. The result is a group of mutant t-PA variants considered third-generation plasminogen activators. TNK-t-PA is one bioengineered variant of t-PA. Another third-generation plasminogen activator is reteplase (r-PA). Like TNK-t-PA, it is a variant of t-PA that has been developed to establish a more rapid, complete, and stable coronary artery patency, thus promising reduced mortality. Both r-PA and TNK-t-PA are effective when given as bolus therapy. This feature may facilitate more rapid treatment as well as decrease overall costs of treatment. New fibrinolytic regimens include potent antiplatelet agents that may improve sustained reperfusion. This review summarizes the latest and often confusing data on the interaction between fibrinolytic therapy and platelets in certain in vitro, animal and clinical scenarios.
纤维蛋白溶解疗法是治疗ST段抬高型急性心肌梗死（AMI）患者的既定方法。目前的纤维蛋白溶解方案存在一些缺点，包括无法实现早期和持续再灌注，以及至少在某些患者中无法预防再闭塞。血小板在导致AMI的冠状动脉血栓形成中起重要作用。冠状动脉纤维蛋白溶解对血小板的影响在文献中已有广泛讨论，有血小板激活和抑制的证据。在纤维蛋白溶解剂中，组织型纤溶酶原激活剂（t-PA）被认为是治疗冠状动脉疾病的主要药物。天然t-PA分子已被修饰，试图在降低出血风险的同时实现更好的溶解特性。结果产生了一组被认为是第三代纤溶酶原激活剂的突变t-PA变体。替奈普酶（TNK-t-PA）是t-PA的一种生物工程变体。另一种第三代纤溶酶原激活剂是瑞替普酶（r-PA）。与TNK-t-PA一样，它是t-PA的变体，已被开发用于建立更快速、完全和稳定的冠状动脉通畅，从而有望降低死亡率。r-PA和TNK-t-PA推注给药时均有效。这一特性可能有助于更快速地治疗并降低总体治疗成本。新的纤维蛋白溶解方案包括可能改善持续再灌注的强效抗血小板药物。本综述总结了在某些体外、动物和临床情况下，关于纤维蛋白溶解疗法与血小板相互作用的最新且常常令人困惑的数据。
