New anticoagulant agents: direct thrombin inhibitors

Decades of research have been devoted to developing effective, safe, and convenient anticoagulant agents. In recent years, much emphasis has been placed on the development of direct thrombin inhibitors (DTIs) that offer benefits over agents like heparin and warfarin including the inhibition of both circulating and clot-bound thrombin; a more predictable anticoagulant response, because they do not bind to plasma proteins and are not neutralized by platelet factor 4; lack of required cofactors, such as antithrombin or heparin cofactor II; inhibiting thrombin-induced platelet aggregation; and absence of induction of immune-mediated thrombocytopenia. Various injectable DTIs are currently available and used for many indications. In addition, research is now focusing on oral DTIs that seem promising and offer various advantages, such as oral administration, predictable pharmacokinetics and pharmacodynamics, a broad therapeutic window, no routine monitoring, no significant drug interactions, and fixed-dose administration.