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Thromb Haemost 1999; 82(05): 1462-1468
DOI: 10.1055/s-0037-1614856
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Schattauer GmbH

Dermatan Sulfate and LMW Heparin Enhance the Anticoagulant Action of Activated Protein C

José A. Fernández   *
1   From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
,
Jari Petäjä   *
1   From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
,
John H. Griffin
1   From the Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
› Author AffiliationsThis study was supported in part by grants from the National Institutes of Health (R37HL52246 and RO1HL21544), the Stein Research Endowment, the Sigrid Jusélius Foundation, the Paulo Foundation and the Finnish Cultural Foundation.
Further Information

Publication History

Received 16 November 1998

Accepted after resubmission 07 July 1999

Publication Date:
09 December 2017 (online)

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Summary

Unfractionated heparin potentiates the anticoagulant action of activated protein C (APC) through several mechanisms, including the recently described enhancement of proteolytic inactivation of factor V. Possible anticoagulant synergism between APC and physiologic glycosaminoglycans, pharmacologic low molecular weight heparins (LMWHs), and other heparin derivatives was studied. Dermatan sulfate showed potent APC-enhancing effect. Commercial LMWHs showed differing abilities to promote APC activity, and the molecular weight of LMWHs correlated with enhancement of APC activity. Degree of sulfation of the glycosaminoglycans influenced APC enhancement. However, because dextran sulfates did not potentiate APC action, the presence of sulfate groups per se on a polysaccharide is not sufficient for APC enhancement. As previously for unfractionated heparin, APC anticoagulant activity was enhanced by glycosaminoglycans when factor V but not factor Va was the substrate. Thus, dermatan sulfate and LMWHs exhibit APC enhancing activity in vitro that could be of physiologic and pharmacologic significance.

Keywords

Dermatan sulfate - heparin - activated protein C - factor V

* The first two authors contributed equally to the studies reported in this paper


 

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