RECOMBINANT SOLUBLE HUMAN THROMBOMODULIN - A RANDOMIZED, BLINDED ASSESSMENT OF PREVENTION OF VENOUS THROMBOSIS AND EFFECTS ON HEMOSTATIC PARAMETERS IN A RAT MODEL

Thrombomodulin is an endothelial surface receptor that binds thrombin and accelerates the activation of protein C. We compared the effects o f a recombinant thrombomodulin analog (TM(E)), recombinant hirudin (r- HIR), heparin sodium (HEP), and normal saline (Control) on thrombus fo rmation, activated partial thromboplastin time (APTT), thrombin time ( TT), platelet aggregation and tail transection bleeding time (BT) in a rat model of vena cava thrombosis. Results: TM(E), r-HIR and HEP prev ented venous thrombosis in this model in a dose-dependent manner. At t he dose required to reduce vena cava thrombosis by 50% (ED(50)), TM(E) did not prolong the APTT or TT as did HEP and r-HIR. Platelet aggrega tion in response to thrombin was not effected by TM(E) but was inhibit ed by both r-HIR and HEP. BT did not differentiate the agents tested. Conclusion: TM(E) inhibited venous thrombosis in a rat vena cava model with less effect on hemostatic variables than HEP or r-HIR.