Pharmacology of Fibrinolysis

Abstract

Fibrinolysis can be achieved pharmacologically with the use of any of the four commercially available plasminogen activators—SK, APSAC, UK, and t-PA. Fibrinolysis with all of these agents is due to their ability to convert plasminogen to plasmin, either in the circulation or on the surface of the thrombus. Each of these plasminogen activators has a slightly different mechanism of action. Despite these mechanistic differences, none of the agents available today is completely "fibrin-specific." Their clinical use is associated with systemic activation of the fibrinolytic mechanism and, consequently, a risk of pathologic bleeding. At clinically applicable doses, all agents are capable of initiating dissolution of thrombi. The rate and extent of thrombus dissolution and fibrinogen degradation vary in different clinical situations, with differing drug doses and routes of administration, and between different drugs. At this time, no one agent has emerged as a superior fibrinolytic agent for all clinical circumstances. [SEE THE FIG10 IN SOURCE PDF] The best drug for treatment of each of the many thrombosis-related disorders must be determined by extensive comparative clinical trials. Given that there are 4 commercially available drugs (without considering the drugs currently in developmental stages) that have not been evaluated extensively at varying doses and dosing intervals, in different combinations, and by various routes and methods of administration in a wide variety of venous and arterial thromboembolic disorders, it is reasonable to conclude that such trials are only in their infancy.