Use of plasminogen activators in venous thrombosis

A major advance in the treatment of thrombosis has been the development of thrombolytic agents. Streptokinase and urokinase have been the standard agents available for many years, but in recent years the most exciting change in the field has been the development of a new generation of plasminogen activators, the principal one being tissue plasminogen activator. The first generation of plasminogen activators--streptokinase and urokinase--do not have fibrin specificity and predictably induce plasma proteolysis when administered systemically in doses which introduce thrombolysis. The second generation of plasminogen activators are much more fibrin-specific and offer a promise of fewer complications. In a number of major randomized studies, these thrombolytic agents have proved effective clinically. The major complication of thrombolytic therapy, however, is hemorrhage. The risk of hemorrhage increases with the length of infusion and occurs most often from sites of vascular invasion such as needle punctures or cutdown sites from surgical wounds. This can be treated by applying pressure over the wound and discontinuing the thrombolytic agent whose half-life is measured in hours. It is believed that as more experience is acquired with the second-generation plasminogen activators, better control of these drugs will result in fewer complications and more effective and wider application of therapy.