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Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2735-2743
A Novel Approach to Arterial Thrombolysis
Petr Klement,
Peng Liao, and
Laszlo Bajzar
From the Hamilton Civic Hospitals Research Centre and McMaster
University, Hamilton, Ontario, Canada.
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 increased concentrations of thrombolytics as well as with
adjunctive antithrombotic and antiplatelet agents. A novel approach to
enhance thrombolytic therapy 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 efficacy of
tissue-plasminogen activator (tPA) alone or with an inhibitor, isolated
from the potato tuber (PTI), of activated TAFI (TAFIa). Efficacy was
assessed by determining the time to patency, the time the vessel
remained patent, the maximal blood flow achieved during therapy, the
percentage of the original thrombus, which lysed, the percentage change
in clot weight, the net clot accreted, and the release of radioactive fibrin degradation products into the circulation. The results indicate
that coadministration of PTI and tPA significantly improved tPA-induced
thrombolysis without adversely affecting blood pressure, activated
partial thromboplastin time, thrombin clotting time, fibrinogen, or
 -2-antiplasmin concentrations. The data indicate that inhibitors of
TAFIa may comprise novel and very effective adjuncts to tPA and improve
thrombolytic therapy to achieve both clot lysis and vessel patency.
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