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Thromb Haemost 1995; 73(05): 805-811
DOI: 10.1055/s-0038-1653872
Original Articles
Coagulation
Schattauer GmbH Stuttgart

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

Yasuo Takahashi
1   The Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Gotemba, Japan
,
Yoshitaka Hosaka
1   The Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Gotemba, Japan
,
Hiromi Niina
1   The Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Gotemba, Japan
,
Katsuaki Nagasawa
1   The Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Gotemba, Japan
,
Masaaki Naotsuka
2   Pharmaceutical Laboratory, Mochida Pharmaceutical Co., Ltd., Fujieda, Japan
,
Kiyoshi Sakai
2   Pharmaceutical Laboratory, Mochida Pharmaceutical Co., Ltd., Fujieda, Japan
,
Akio Uemura
1   The Fuji Central Research Laboratory, Mochida Pharmaceutical Co., Ltd., Gotemba, Japan
› Author Affiliations
Further Information

Publication History

Received 26 September 1994

Accepted after revision 06 February 1995

Publication Date:
09 July 2018 (online)

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Summary

We examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein 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 fibrinogen 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 appeared 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 hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

 

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