Optimization of thrombin inhibition: introduction to the mechanism of action of direct thrombin inhibitors - Beliefs and facts

An extensive and improved knowledge of blood coagulation processes is the key to the design and the development of antithrombotic drugs. New molecules have been designed to be more selective in their biological target, and to be more homogeneous in biochemical structure, in order to improve the efficacy and safety of antithrombotic strategy. Thrombin is the cornerstone of thrombotic and fibrinolytic processes, and during clot formation thrombin, as well as FXa is trapped in the fibrin network and bound to fibrin. Fibrin-bound thrombin also contributes to thrombus progression. The reduction of thrombin generation and the direct inhibition of its activity are primary targets for effective antithrombotic treatment. Inhibition of both free and clot bound thrombin is an important characteristic of argatroban. In addition, argatroban has a short halflife and non-renal clearance. This article will review the main mechanisms of action of direct thrombin inhibitors and focus on argatroban.