Development of argatroban as an anticoagulant and antithrombin agent in Japan

Argatroban is a synthetic direct thrombin inhibitor which has been used in Japan for three indications, namely, chronic arterial occlusion, acute cerebral thrombosis and hemodialysis in AT-deficient patients or in patients with decreased AT. In patients with chronic arterial occlusion, argatroban increased the skin temperature, reduced the size of skin ulcers, and decreased the thrombin-antithrombin complex. In patients with acute cerebral thrombosis, neuronal symptoms improved significantly compared with the placebo group, wherein activated partial thromboplastin time (aPTT) was prolonged by about 1.5-fold and fibrinopeptide A was reduced. In some patients in whom hemodialysis is difficult due to the generation of blood clots in the dialyzer, hemodialysis is now possible with the replacement of heparin by argatroban.