Antithrombin Agents as Anticoagulants and Antithrombotics: Implications in Drug Development

Abstract

Antithrombin agents of recombinant and synthetic origin are now validated in experimental models as useful an ticoagulant and antithrombic drugs. Several clinical trials in cluding surgical anticoagulation, management of coronary syn dromes, adjunct to thrombolytic agents and treatment of throm boembolism have also shown the comparative efficacy of these agents in reference to heparin. Argatroban and hirudin are now available for specific clinical indications such as thrombotic and ischemic stroke and alternate anticoagulants for heparin- induced thrombocytopenia (HIT) patients in Japan and Euro pean countries, respectively. While these agents produce strong anticoagulant effects, their mechanism of action is distinct from that of heparins, thus these agents should be used carefully using specific guidelines provided for each product. Thrombin inhibitors are effective anticoagulants however, their therapeu tic index is narrower than heparin and as such their nonopti mized use is potentially associated with hemorrhagic compli cations.