Effect of Argatroban versus Recombinant Hirudin on Tissue-Factor-Mediated Thrombin Generation: An in Vitro Study

Argatroban, a synthetic chemical compound, and recombinant hirudin (r-hirudin) are both direct thrombin inhibitors. Their actions are reversible and irreversible, respectively. We studied the influence of these two anticoagulants on the thrombin generation test using the method according to Hemker. For this investigation, a pool of citrated, platelet-poor, normal human plasma was supplemented with each drug at increasing concentrations. r-Hirudin had a dramatic influence on the initiation phase with almost no effect on the peak thrombin generated or the endogenous thrombin potential (ETP). In contrast, argatroban prolonged the initiation phase of thrombin generation and decreased the peak and ETP values. These differences are attributable to the irreversible and reversible binding to thrombin of these agents. This study reveals clear distinctions between the mechanisms of these two thrombin inhibitors. KEYWORDS Thrombin generation - argatroban - hirudin - thrombin inhibitors