Future Directions

Older agents, though effective, still have limitations such as risks of intracranial hemorrhage and 5-15% reocclusion rate. Ongoing efforts to develop newer thrombolytics that overcome the limitations seen with older agents are underway. Ideally, new thrombolytic agents should: (1) be fibrin specific; (2) be directed to newly formed fibrin without affecting normal hemostasis; (3) be nonantigenic; (4) be cost effective; and (5) have rapid onset. One such agent is BB-10153, an engineered variant of human plasminogen that is modified to be activated to plasmin by thrombin (a.k.a thrombin-activatable plasminogen). It was designed to act as a prodrug, persisting in the blood and activating only plasmin in fresh or forming thrombi. In essence, it should only act on clot-bound thrombin. Consequently, thrombus dissolution may be achieved without systemic destruction of hemostatic proteins, thus potentially reducing the risk of haemorrhage. The plasma half-life of BB-10153 was found to be 3-4h and it also had no effect on plasma a2-antiplasmin or fibrinogen levels, coagulation assays, or bleeding time. The long half-life and thrombus-selective thrombolytic activity of BB-10153 are promising and might allow it to overcome the bleeding and reocclusion shortfalls in the performance of current thrombolytics.83'84

Essentially, development of newer agents and an approach using a combination of pharmacological and mechanical strategies would increase the rates of recannalization, enhance the reversal of acute coronary syndromes, and improve patient outcomes.

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