Experimentelle und klinische Befunde mit dem Thrombinhemmer Argatroban

Zusammenfassung

Argatroban ist ein niedermolekularer Thrombinhemmer. Wesentliche Eigenschaften dieses synthetisch hergestellten Medikaments sind schnelles Einsetzen der antithrombotischen Wirkung, schnelles Abklingen der gerinnungshemmenden Wirkung, die Hemmung gerinnselgebundenen Thrombins und fehlende Antikörperbildung. Bei Patienten mit Niereninsuffizienz ist keine Dosisanpassung notwendig. Argatroban wird in der Leber metabolisiert. Das Ausmaß der gerinnungshemmenden Wirkung bei intravenöser Anwendung ist vorhersagbar. Argatroban ist in den USA und Kanada zur Prophylaxe und Therapie von Thrombosen bei Patienten mit heparininduzierter Thrombozytopenie (HIT) zugelassen. Außerdem ist es in den USA auch als Antikoagulans während perkutaner koronarer Interventionen bei Patienten mit HIT oder HIT in der Vorgeschichte zugelassen. Vorläufige Berichte zeigen, dass Argatroban zur Gerinnungshemmung während einer Hämodialyse und als Antikoagulans während der thrombolytischen Behandlung des Herzinfarkts eingesetzt werden kann. Zum therapeutischen Monitoring eignet sich die aPTT (aktivierte partielle Thromboplastinzeit) für niedrige und die ACT (aktivierte Gerinnungszeit) für hohe Dosen. Die ECT (Ecarin-Gerinnungszeit) erlaubt die spezifische Messung der thrombinhemmenden Wirkung.

Summary

Argatroban is the smallest anticoagulant molecule of direct thrombin inhibitors. The main attributes of this synthetic drug are its rapid onset of anti-thrombin action, the rapid reversibility of its anticoagulant effect, potent inhibition of clot-bound thrombin, the absence of antibody formation and no need for dosage adjustment in patients with renal impairment. It is eliminated by hepatic metabolism. These properties make argatroban a predictable anticoagulant with intravenous use in a routine clinical setting. Argatroban is approved in the US and Canada for both prophylaxis and treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT) and in the US as an antithrombotic agent during percutaneous coronary interventions in patients with HIT or a history of HIT. Preliminary reports document the feasibility of using argatroban for anticoagulation during hemodialysis and as adjunct to thrombolysis for treatment of myocardial infarction. Current recommendations for argatroban monitoring are to use the aPTT (activated partial thromboplastin time) for low doses and the ACT (activated clotting time) for high doses. The specific inhibition of thrombin can be measured with the ECT (ecarin clotting time).

Schlüsselwörter

Argatroban - Thrombinhemmer - heparininduzierte Thrombozytopenie - Gerinnungshemmung

Keywords

Argatroban - thrombin inhibitor - heparin-induced thrombocytopenia - coagulation inhibitor

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