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Thromb Haemost 1995; 73(03): 405-412
DOI: 10.1055/s-0038-1653789
Original Articles
Coagulation
Schattauer GmbH Stuttgart

Inhibition of Thrombin by Antithrombin III and Heparin Cofactor II In Vivo

Longbin Liu
1   The Canadian Red Cross Society, Blood Services, Hamilton, Canada
2   Department of Pathology, McMaster University, Hamilton, Canada, New York
,
Lori Dewar
1   The Canadian Red Cross Society, Blood Services, Hamilton, Canada
,
Yingqi Song
2   Department of Pathology, McMaster University, Hamilton, Canada, New York
,
Myron Kulczycky
2   Department of Pathology, McMaster University, Hamilton, Canada, New York
,
Blajchman A Morris
1   The Canadian Red Cross Society, Blood Services, Hamilton, Canada
2   Department of Pathology, McMaster University, Hamilton, Canada, New York
3   Department of Pathology, McMaster University, Hamilton, Canada, New York
,
John W Fenton
4   Department of Health, Albany, U.S.A.
,
Maureen Andrew
5   Department of Paediatrics, McMaster University, Hamilton, Canada, New York
,
M Delorme
3   Department of Pathology, McMaster University, Hamilton, Canada, New York
,
Jeffrey Ginsberg
3   Department of Pathology, McMaster University, Hamilton, Canada, New York
,
Klaus T Preissner
6   Department of Haemostasis Research, Kerckhoff-Klinik, Max-Plank-Gesellschaft, Bad Nauheim, Germany
,
Frederick A Ofosu
1   The Canadian Red Cross Society, Blood Services, Hamilton, Canada
2   Department of Pathology, McMaster University, Hamilton, Canada, New York
› Author Affiliations
Further Information

Publication History

Received27 July 1994

Accepted after resubmission 29 November 1994

Publication Date:
09 July 2018 (online)

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Summary

The critical role of thrombin in the pathogenesis of venous and arterial thrombosis, and the effectiveness of glycosaminoglycans as antithrombotic drugs are well known. Antithrombin III is a major inhibitor of thrombin and augmentation of its inhibitory actions by heparin is the basis for the clinical uses of heparin. Recent clinical and experimental studies have demonstrated that another glycosaminoglycan, dermatan sulfate, is an effective antithrombotic drug. Dermatan sulfate catalyses the inhibition of thrombin by heparin cofactor II. The concentrations of heparin cofactor II are higher in the plasmas of individuals with congenital antithrombin III deficiency and pregnant women than controls. The role of heparin cofactor II as a physiologic thrombin inhibitor is unknown. Enzyme-linked immunosorbent assays were used to quantify thrombin-heparin cofactor II and thrombin-antithrombin III endogenous to the plasmas of adult antithrombin III-Hamilton deficient subjects, their siblings with normal antithrombin III levels, pregnant women at term and 3 to 5 days after delivery. Both thrombin-antithrombin III and thrombin-heparin cofactor II complexed with vitronectin were detected in all the plasmas. Significantly, the concentrations of thrombin-heparin cofactor II-vitronectin were higher in the plasmas of congenital antithrombin III deficient subjects and in pre- and post-delivery plasmas than those of normal subjects. In addition, the concentrations of thrombin-heparin cofactor II decreased 3 to 5 days after delivery, reflecting the disappearance of the catalytically active dermatan sulfate elaborated by the placenta. Thus, heparin cofactor II normally inactivates thrombin in vivo, with its role increasing in conditions associated with high levels of heparin cofactor II and/or dermatan sulfate.

 

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