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Thromb Haemost 1988; 59(02): 295-298
DOI: 10.1055/s-0038-1642774
Original Articles
Schattauer GmbH Stuttgart

Standard Heparin Enhances the Antithrombotic Activity of Dermatan Sulfate in the Rabbit but CY 216 Does Not

Y Cadroy
1   Laboratoire d’Hemostase, Centre de Transfusion Sanguine, Toulouse, France
,
F Dol
1   Laboratoire d’Hemostase, Centre de Transfusion Sanguine, Toulouse, France
,
C Caranobe
1   Laboratoire d’Hemostase, Centre de Transfusion Sanguine, Toulouse, France
,
M Petitou
2   Institut Choay, Paris, France
,
J C Lormeau
2   Institut Choay, Paris, France
,
P Sié
1   Laboratoire d’Hemostase, Centre de Transfusion Sanguine, Toulouse, France
,
J Choay
2   Institut Choay, Paris, France
,
B Boneu
1   Laboratoire d’Hemostase, Centre de Transfusion Sanguine, Toulouse, France
› Author Affiliations
Further Information

Publication History

Received 13 October 1987

Accepted after revision 21 December 1987

Publication Date:
21 May 2018 (online)

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Summary

Standard heparin (SH) and dermatan sulfate (DS) two gly- cosaminoglycans with different pharmacological targets are effective antithrombotic agents in the rabbit. We have investigated the antithrombotic activity of the association DS plus SH. It was found that doses as low as 25 µg/kg for DS and 10 µg/kg for SH were ineffective when injected separately but generated a high and significant antithrombotic activity when injected together. These results were confirmed when higher doses of each compound were delivered in association. Further experiments were performed to determine if the enhancement of the antithrombotic activity of DS by HS resulted from its anti-factor Ha or antifactor Xa activity or from its moiety without affinity to AT III. A low molecular weight heparin (CY 216) with an anti-factor Xa/ anti-factor Ha ratio of 5, the synthetic pentasaccharide bearing the minimum binding sequence to antithrombin III, and a low affinity fraction of SH to AT III did not increase the antithrombotic activity of DS; in contrast a high affinity fraction of SH to AT III had the same effect than SH. We conclude that the enhancement of the antithrombotic activity of DS by SH mainly results from its anti-factor IIa activity.

Keywords

Heparin - Heparin derivatives - Dermatan sulfate - Thrombus prevention
 

  • References

  • 1 Buchanan MR, Boneu B, Ofosu F, Hirsh J. The relative importance of thrombin inhibition and factor Xa inhibition to the antithrombotic effects of heparin. Blood 1985; 65: 198-201
    PubMedGoogle Scholar
  • 2 Fernandez F, Van Ryn J, Ofosu FA, Hirsh J, Buchanan MR. The haemorrhagic and antithrombotic effects of dermatan sulphate. Br J Haemat 1986; 64: 309-317
    CrossrefPubMedGoogle Scholar
  • 3 Van Ryn-McKenna J, Gray E, Weber E, Ofosu FA, Buchanan MR. The effects of sulfated polysaccharides on inhibition of thrombosis by different stimuli. Thromb Haemostas 1987; 58: 7-7 Abstr 25
    PubMedGoogle Scholar
  • 4 Merton RE, Barrowcliffe TW, Thomas DP. A comparison of dermatan sulfate and heparin as antithrombotic drugs. Thromb Haemostas 1987; 58: 36-36 Abstr 134
    PubMedGoogle Scholar
  • 5 Morani A, Gianese F, Bianchini P. Kinetics of experimental antithrombotic activity of MF 701 dermatan sulfate. Thromb Haemostas 1987; 58: 124-124
    PubMedGoogle Scholar
  • 6 Rozenberg RD. Heparin-antithrombin system. In: Hemostasis and thrombosis basic principles and clinical practice. Coleman RW, Hirsh J, Marder VF, Salzman EW. (eds.) pp 962-985 JP Lippincot company; Philadelphia, Toronto: 1982
    Google Scholar
  • 7 Tollefsen DS, Pestka CA, Monafo WJ. Activation of heparin cofactor II by dermatan sulfate. J Biol Chem 1983; 258: 6713-6716
    PubMedGoogle Scholar
  • 8 Choay J, Petitou M, Lormeau JC, Sinay P, Casu B, Gatti G. Structure-activity relationship in heparin: a synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity. Biochem Biophys Res Com 1983; 116: 492-499
    CrossrefPubMedGoogle Scholar
  • 9 Hook M, Bjork I, Hopwood J, Lindahl U. Anticoagulant activity of heparin: separation of high-activity and low-activity heparin-speciesby affinity chromatography on immobilized antithrombin. Febs Letters 1976; 66: 90-93
    CrossrefPubMedGoogle Scholar
  • 10 Carter CJ, Kelton JG, Hirsh J, Cerskus A, Santos AV, Gent M. The relationship between the hemorrhagic and antithrombotic properties of low molecular weight heparin in rabbits. Blood 1982; 59: 1239-1245
    PubMedGoogle Scholar
  • 11 Ockelford P, Carter CJ, Mitchell L, Hirsh J. Discordance between the anti-Xa activity and the antithrombotic activity of an ultra low molecular weight heparin fraction. Thromb Res 1982; 28: 401-409
    CrossrefPubMedGoogle Scholar
  • 12 Cade JF, Buchanan MR, Boneu B, Ockelford P, Carter CJ, Cerskus AL, Hirsh J. A comparison of the antithrombotic and haemorrhagic effects of low molecular weight heparin fractions: the influence of the method of preparation. Thromb Res 1984; 35: 613-625
    CrossrefPubMedGoogle Scholar
  • 13 Wallenga JM, Petitou M, Lormeau JC, Samama M, Fareed J, Choay J. Antithrombotic activity of a synthetic pentasaccharide in a rabbit stasis thrombosis model using different thrombogenic challenges. Thromb Res. 1987 in press
    PubMedGoogle Scholar
  • 14 Merton RE, Thomas DP, Havercroft SJ, Barrowcliffe TW, Lindhal U. High and low affinity heparin compared with unfractionated heparin as antithrombotic drugs. Thromb Haemostas 1984; 51: 254-256
    PubMedGoogle Scholar
  • 15 Sie P, Ofosu F, Fernandez F, Buchanan MR, Petitou M, Boneu B. Respective role of antithrombin III and heparin cofactor II in the in vitro anticoagulant effect of heparin and various sulphated polysaccharides. Brit J Haematol 1986; 64: 707-714
    CrossrefPubMedGoogle Scholar
  • 16 Hemker HC. The mode of action of heparin in plasma. In: Thrombosis and Haemostasis 1987. Verstraete M, Vermylen J, Lijnen R, Arnout J. (eds.) pp 17-36 Leuven University Press. 1987
    Google Scholar