Regulation and Dysregulation of Fibrinolysis

Abstract

Hemostasis is a dynamic equilibrium between coagulation and fibrinolysis. The coordinated interplay of primary hemostasis, secondary hemostasis, and fibrinolysis ensures arrest of bleeding, restoration of vascular patency, and wound healing following injury. Plasmin, formed from its zymogenic form plasminogen by the action of plasminogen activators derived from the endothelium, plays a central role in fibrinolysis. The endogenous plasminogen activators are tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Regulation of fibrinolysis involves protease action, serpin inactivation, and conformational changes. In disseminated intravascular coagulation (DIC), both the processes of coagulation and fibrinolysis are dysregulated. The dysregulated fibrinolytic process in sepsis, manifested by an increased level of plasminogen activator inhibitor-1, can be targeted for therapeutic intervention and by supplementing the decreased endogenous anticoagulant agents such as APC, AT, and TFPI. The important implication of the intricacies of regulation and dysregulation of fibrinolysis is in the cautious use of fibrinolytic drugs especially in neurosurgical patients.