Combined administration of aspirin and a specific thrombin inhibitor in man.

Abstract

Background. Heparin is of limited value as an antithrombotic drug in the presence of platelet activation and residual thrombus. Greater anticoagulant activity can be achieved in vivo with more specific thrombin inhibitors. Heparin may also increase the risk of bleeding by an effect on platelets that is independent of its thrombin inhibitory activity.Methods and Results. The pharmacodynamic and pharmacokinetic effects of a novel thrombin inhibitor, argatroban, were examined alone and in combination with aspirin in normal male volunteers. Argatroban induced a dose-dependent prolongation of the thrombin time and the activated partial thromboplastin time (aPWT). aPTT had returned to its pretreatment value 1 hour after stopping the infusion of argatroban. Six male subjects received an infusion of 1

Antithrombotic actions of argatroban in rat models of venous, ‘mixed’ and arterial thrombosis, and its effects on the tail transection bleeding time

“…has been performed on the actions of argatroban in purely erythrocyte-rich venous, 'mixed' (platelet-and erythrocyterich), and arterial thrombosis models in the same species. Moreover, unlike heparin, argatroban has a short duration of action both in animals and in man (Iida et al, 1986;Verstraete, 1990;Clarke et al, 1991); thus, in order to ascertain its real antithrombotic efficacy, it is necessary to administer the compound by intravenous infusion. We therefore studied the antithrombotic action of intravenous argatroban, both as a bolus and as an infusion, in three models of thrombosis in the rat: the Wessler model (Wessler et al, 1959), transposed to the rat by Freund et al (1990), which is a model of venous thrombosis; an arteriovenous shunt containing a thrombogenic surface where thrombus formation depends upon both platelet and coagulation activation ('mixed' thrombus; Peters et al, 1991); and a model of platelet-rich thrombosis induced by deep intimal lesion of the left common carotid artery.…”

Introduction - A Brief Overview of Selected Aspects of Colonoscopy: Past, Present and Future

“…Newer anticoagulants, for which current guidelines regarding their being held for endoscopic procedures are lacking, are reaching the market at an increasing rate. These include danaparoid, a low molecular weight heparinoid consisting of a mixture of heparan sulfate, dermatan sulfate, and chondroitin sulfate (Danhof et al, 1992, Nurmohamed, et al, 1991 which was recently removed from the US market due to shortages; the direct thrombin inhibitors recombinant hirudin (lepirudin), argatroban, desirudin and bivalirudin (Greinacher & Warkentin, 2008, Clarke, et al, 1991, Warkentin, et al, 2008; the recently available orally active direct thrombin inhibitor dabigatran etexlate (Schulman, et al, 2009); and the factor XA inhibitors idraparinux, rivaroxaban, and apixaban (Turpie, 2008).…”

Medicamentos alternativos e novos fármacos

“…Atinge uma rápida eficácia terapêutica antitrombótica, com um mínimo risco de sangramento e rápida restauração da hemostasia no momento da descontinuação. (17) A argatrobana tem meia-vida curta e, como a ligação com a trombina é reversível, torna-o mais seguro e com menor risco de sangramento em relação à hirudina recombinante. (18) É necessária precaução em pacientes portadores de disfunção hepática, já que essa é a via de excreção.…”