SPECIES-SPECIFICITY OF THE ANTICOAGULANT ACTIVITY OF HUMAN URINARY SOLUBLE THROMBOMODULIN

The anticoagulant activities of human urinary soluble thrombomodulin ( UTM) in blood taken from various species using several anticoagulant a ssay systems were compared; it was examined which coagulant assay syst em is appropriate for evaluation of the antithrombotic effects of UTM and how the species specificity of UTM is involved in the mechanisms o f action of UTM. When anticoagulant activities were compared using act ivated partial thromboplastin time (APTT), thromboelastography (TEG), and thrombin generation test (TGT), the effect of UTM was found to be the strongest in humans among various species tested. Among the antico agulant assays tested, TGT reflecting protein C (PC) activation by UTM , appeared to be more sensitive than APTT and TEG in detection of thro mbomodulin activity. In the study of the mechanisms of action of UTM, UTM exhibited nearly the same antithrombin activity against human and rat thrombin; the rate of activation of human PC by thrombin/UTM compl ex was much higher than that of rat PC. Therefore, the species specifi city of the anticoagulant activity of UTM may be attributable to throm bin/UTM-PC interaction, but not to UTM-thrombin interaction. From thes e results, we concluded that TGT reflecting PC activation by UTM will be a more useful assay than APTT and TEG for estimating the antithromb otic effects of UTM in humans. Furthermore, our findings suggest that UTM will exhibit more potent antithrombotic effects in humans than tho se in rats by strongly enhancing thrombin-catalyzed PC activation. (C) 1998 Elsevier Science Ltd.