(Pharmacotherapy 2002;22(4):433-435)Direct thrombin inhibitors such as lepirudin, bivalirudin, and argatroban constitute a novel class of anticoagulants. The mechanism of action of these agents differs from heparin in that they directly inhibit the active site of thrombin, and they do not require an interaction with antithrombin III to produce their anticoagulant effect.1 Furthermore, contrary to heparin, these agents inhibit only the activity of thrombin whereas heparin, through its activation of antithrombin III, indirectly inhibits factors IIa (thrombin), Xa, IXa, XIa and XIIa.