A novel approach to arterial thrombolysis

Achieving early, complete, and sustained reperfusion after acute myocardial infarction does not occur in approximately 50% of patients, even with the most potent established thrombolytic therapy. Bleeding is observed with inc reased concentrations of thrombolytics as well as with adjunctive antithrom botic and antiplatelet agents. A novel approach to enhance thrombolytic the rapy is to inhibit the activated form of thrombin-activatable fibrinolysis inhibitor (TAFI), which attenuates fibrinolysis in clots formed from human plasma. Identification of TAFI in rabbit plasma facilitated the development of a rabbit arterial thrombolysis model to compare the thrombolytic effica cy of tissue-plasminogen activator (tPA) alone or with an inhibitor, isolat ed from the potato tuber (PTI), of activated TAFI (TAFIa). Efficacy was ass essed by determining the time to patency, the time the vessel remained pate nt, the maximal blood flow achieved during therapy, the percentage of the o riginal thrombus, which lysed, the percentage change in clot weight, the ne t clot accreted, and the release of radioactive fibrin degradation products into the circulation. The results indicate that coadministration of PTI an d tPA significantly improved tPA-induced thrombolysis without adversely aff ecting blood pressure, activated partial thromboplastin time, thrombin clot ting time, fibrinogen, or alpha-2-antiplasmin concentrations, The data indi cate that inhibitors of TAFIa may comprise novel and very effective adjunct s to tPA and improve thrombolytic therapy to achieve both clot lysis and ve ssel patency. (C) 1999 by The American Society of Hematology.