Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, 80135 Naples, Italy.
Int J Mol Sci. 2022 May 28;23(11):6065. doi: 10.3390/ijms23116065.
Traditionally, platelets have been exclusively considered for their procoagulant and antifibrinolytic effects during normal activation of hemostasis. Effectively, activated platelets secrete coagulation factors, expose phosphatidylserine, and promote thrombin and fibrin production. In addition to procoagulant activities, platelets confer resistance of thrombi to fibrinolysis by inducing clot retraction of the fibrin network and release of huge amounts of plasminogen activator inhibitor-1, which is the major physiologic inhibitor of the fibrinolytic cascade. However, the discovery of multiple relations with the fibrinolytic system, also termed Plasminogen Activation System (PAS), has introduced new perspectives on the platelet role in fibrinolysis. Indeed, the activated membrane surface of platelets provides binding sites on which fibrinolytic enzymes can be activated. This review discusses the evidence of the profibrinolytic properties of platelets through the description of PAS components and related proteins that are contained in or bind to platelets. Our analyses of literature data lead to the conclusion that in the initial phase of the hemostatic process, antifibrinolytic effects prevail over profibrinolytic activity, but at later stages, platelets might enhance fibrinolysis through the engagement of PAS components. A better understanding of spatial and temporal characteristics of platelet-mediated fibrinolysis during normal hemostasis could improve therapeutic options for bleeding and thrombotic disorders.
传统上，血小板在正常止血过程中的激活中仅被认为具有促凝和抗纤维蛋白溶解作用。实际上，活化的血小板会分泌凝血因子、暴露磷脂酰丝氨酸，并促进凝血酶和纤维蛋白的生成。除了促凝作用外，血小板还通过诱导纤维蛋白网络的凝块回缩和大量纤溶酶原激活物抑制剂-1 的释放，赋予血栓对纤维蛋白溶解的抗性，纤溶酶原激活物抑制剂-1 是纤维蛋白溶解级联的主要生理抑制剂。然而，通过描述包含在血小板中或与血小板结合的纤溶系统（也称为纤溶酶原激活系统，PAS）的多个相关成分和相关蛋白，发现了血小板在纤维蛋白溶解中的新作用。本综述通过描述包含在血小板中或与血小板结合的纤溶系统（也称为纤溶酶原激活系统，PAS）的多个相关成分和相关蛋白，讨论了血小板具有抗纤维蛋白溶解特性的证据。我们对文献数据的分析得出的结论是，在止血过程的初始阶段，抗纤维蛋白溶解作用占主导地位，超过了纤维蛋白溶解活性，但在后期阶段，血小板可能通过激活 PAS 成分来增强纤维蛋白溶解。更好地了解正常止血过程中血小板介导的纤维蛋白溶解的时空特征，可能会改善出血和血栓形成障碍的治疗选择。
