Natural inhibitors of fibrinolysis

Abstract

I NTRAVASCULAR fibrin deposits or thrombus formation is a major pathophysiologic phenomenon in health and disease. The dissolution of such fibrin deposits or thrombi in vivo is achieved by plasmin formed from plasminogen by plasminogen activator that has been added extrinsically for the therapeutic purposes (urokinase and streptokinase) or endogenously generated in the vascular trees (blood activators or vascular activator). Regardless of the manner in which plasminogen is activated dissolution of fibrin is believed to be checked or retarded by natural inhibitors of fibrinolysis. Natural inhibitors of fibrinolysis inhibit the activation of plasminogen to plasmin or act upon the plasmin already formed. Although the presence versus absence of the former inhibitors in plasma has been a subject of debate, the presence of inhibitors of plasmin has been firmly established. The presence in tissues of inhibitors acting upon plasminogen activator is also known. There are synthetic inhibitors (epsilon-amino caproic acid, tranexamic acid, etc.) and bovine trypsin inhibitor (aprotinin) available for therapeutic purposes in the regulation of fibrinolysis. These extrinsic inhibitors are beyond the scope of this review and only endogenously occurring inhibitors of fibrinolysis in man will be discussed.