Regulation of fibrinolysis by platelets

The manner by which platelets support and regulate aspects of the fibrinolytic system is perhaps underappreciated in comparison to their well-defined function in coagulation. In this chapter we explore the ability of platelets to regulate fibrinolysis in a positive and negative manner by several key mechanisms including: (1) Secretion of various key proteins and molecules during platelet activation, the most studied of which is the serpin, plasminogen activator inhibitor 1 (PAI-1). (2) Anchoring of fibrinolytic proteins to the site of action, akin to the situation in coagulation, which augments plasminogen activation via binding of plasminogen, plasminogen activators and proteins of the contact pathway. (3) Their impact on clot structure, with areas of fibrin immediately adjacent to platelets being dense in nature, which hinders progression of lysis. (4) Regulation of clot retraction through a series of extracellular and intracellular interactions between fibrinogen and the actin cytoskeleton coordinated through the integrin αIIbβ3. The net impact of these reactions is difficult to gauge as it is most likely dictated by platelet concentration and their spatio-temporal distribution, solute transport, degree of activation as well as the expression and binding of proteins to the platelet surface.