[Antithrombotic effect of recombinant human thrombomodulin on experimentally induced thrombosis in rats]

Antithrombotic effect of recombinant human thrombomodulin (TM) on experimentally induced thrombosis in mice was studied. The soluble recombinant human TM (TMD 123), which was expressed in Chinese hamster ovary cells and purified from the conditioned medium, prolonged thrombin clotting time for mouse plasma in a dose-dependent fashion. Thrombosis was induced by the injection of lipopolysaccharide (LPS) from E. coli into a lateral tail vein of mice and was identified as disseminated intravascular coagulation (DIC) syndrome by hematological and histological examinations. Simultaneous injection of TMD 123 with LPS into another lateral tail vein of mice significantly corrected the hematological abnormalities compatible with DIC, and also corrected the histological abnormalities i. e. fibrin deposition and decrease of cellular TM in the target organs including kidney, liver and lung. These results indicate that recombinant human TM is a potent antithrombotic agent and that this would be an expectative anticoagulant for DIC or thrombosis in man.