SOLUBLE THROMBOMODULIN PURIFIED FROM HUMAN URINE EXHIBITS A POTENT ANTICOAGULANT EFFECT IN-VITRO AND IN-VIVO

We examined the anticoagulant activity of two major molecules of solub le thrombomodulin purified from human urine. The apparent molecular we ights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for prote in C activation [specific activity > 5,000 thrombomodulin units (TMU)/ mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fi brinogen clotting time (> 1 TMU/ml), APTT (> 5 TMU/ml), TT (> 5 TMU/ml ) and PT (> 40 TMU/ml) in a dose-dependent fashion. These effects appe ared in the concentration range of soluble thrombomodulins present in human plasma and urine, In the rat DIC model induced by thromboplastin , administration of UTMs by infusion (300-3,000 TMU/kg) restored the h ematological abnormalities derived from DIC in a dose-dependent fashio n, These results demonstrate that UTMs exhibit potent anticoagulant an d antithrombotic activities, and could play a physiologically importan t role in microcirculation.