• Thrombosis research · Apr 2002

    Randomized Controlled Trial Comparative Study Clinical Trial

    Absence of paradoxical thrombin activation by fibrin-specific thrombolytics in acute myocardial infarction: comparison of single-bolus tenecteplase and front-loaded alteplase.

    • Sebastian Szabo, Ronald Letsch, Raila Ehlers, Thomas Walter, Silke Kazmaier, Uwe Helber, and Hans Martin Hoffmeister.
    • Medizinische Klinik II, Städtisches Klinikum Solingen, Gotenstr 1, 42653 Solingen, Germany. KrisztinaSzb@aol.com
    • Thromb. Res. 2002 Apr 15;106(2):113-9.

    ObjectivesThrombolytic therapy in patients with acute myocardial infarction is hampered by bleeding complications and procoagulant effects favoring early reocclusion. TNK-tPA was shown in vitro to have considerable fibrin specificity. We investigated the effects of tenecteplase (TNK-tPA) and alteplase (rt-PA) on the haemostasis and fibrinolytic system.Methods And ResultsWe enrolled 30 patients with AMI into the study. Twenty patients received front-loaded rt-PA up to 100 mg; 10 patients were given TNK-tPA in a single bolus up to 50 mg. All patients received aspirin and intravenous heparin. During the first 2 days, the following parameters were repetitively determined: thrombin-antithrombin III complexes (TAT), antithrombin III (ATIII), prothrombin fragment F 1 + 2 (F 1 + 2), kallikrein-like activity (KK), activated factor XII (FXIIa), plasmin alpha 2-antiplasmin complexes (PAP), fibrinogen, D-dimers (DD), tissue-type plasminogen activator (t-PA). A total of 75 healthy persons served as control group. TAT increased significantly after rt-PA but not after TNK-tPA (3 h: 38.1 +/- 29.4 versus 10.5 +/- 4.2 microg/l; p < 0.01), indicating paradoxical thrombin activation. F 1 + 2 increased transiently after rt-PA but not after TNK-tPA. Fibrinogen was significantly lower after rt-PA versus TNK-tPA (3 h: 163 +/- 27 versus 380 +/- 54 mg/dl; p < 0.05). KK activities in the rt-PA group were significantly (p < 0.01) increased over 48 h versus TNK-tPA. PAP and D-dimers were lower over the time course of 48 h in the tenecteplase group versus rt-PA.ConclusionsThis study indicates that tenecteplase has higher fibrin specificity not only in vitro but also in vivo versus alteplase. TNK-tPA consecutively has no paradoxical systemic procoagulant effect due to the lower extent of activation of the kallikrein-factor XII system than alteplase.Copyright 2002 Elsevier Science Ltd.

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