Role of Plasminogen Activation System in Platelet Pathophysiology: Emerging Concepts for Translational Applications

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.