ATIII-independence of anticoagulant effect of human urinary soluble thrombomodulin

We investigated antithrombin III (ATIII)-dependency of the anticoagulant ef fects of human urinary soluble thrombomodulin (UTM) both in vivo and in vit ro, in comparison with those of heparins. For neutralization of rat plasma ATIII activity, we used F(ab')(2) fragment of anti-rat ATIII antibody and c ould establish an appropriate in vivo model to evaluate the ATIII-dependenc y of antithrombotic agents. The efficacy of UTM on thromboplastin-induced d isseminated intravascular coagulation produced in ATIII-decreased rats was almost the same as that in normal rats, whereas unfractionated (UF)-heparin remarkably diminished its effect in ATIII-decreased rats. The prolongation effect of UTM on activated partial thromboplastin time or prothrombin time in plasma in vitro was unchanged in both normal and ATIII-decreased rats, but the effect of UF-heparin remarkably diminished in ATIII-decreased rat p lasma. Such ATIII-independence in the anticoagulant effect of UTM was also observed in human plasma. Thus, differing from heparins, since the anticoag ulant effect of UTM does not depend on plasma ATIII activity, UTM is expect ed to be a useful antithrombotic agent for the treatment of thromboembolic diseases, even in the case with low plasma ATIII activity. (C) 1999 Lippinc ott Williams & Wilkins.