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Thromb Haemost 1990; 64(02): 290-293
DOI: 10.1055/s-0038-1647303
Original Article
Schattauer GmbH Stuttgart

Potentiation of the Antithrombotic Action of Dermatan Sulphate by Small Amounts of Heparin

D P Thomas
The Division of Haematology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, U.K.
,
E Gray
The Division of Haematology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, U.K.
,
R E Merton
The Division of Haematology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, U.K.
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Further Information

Publication History

Received 11 December 1989

Accepted after revision02 May 1990

Publication Date:
25 July 2018 (online)

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Summary

We have examined the effect in impairing thrombus formation of a preparation of dermatan sulphate (DS) alone and DS plus small amounts of unfractionated heparin (UFH). In rabbits given a dose of 150 μg/kg of DS alone, there was minimal reduction in serum-induced stasis thrombosis (Wessler model), with an overall score of 92.5% (100% = no impairment of thrombus formation). When the same dose of DS containing UFH was given (two different subgroups given DS containing 0.25 and 2.5% heparin by dry weight, respectively), the overall thrombus score was reduced to 60% (P <0.003), with no significant difference between the two subgroups. To achieve a comparable result with DS alone, a dose of 1 mg/kg was required. We conclude that very small amounts of UFH significantly enhance the antithrombotic action of DS, by a mechanism that has yet to be determined.

 

  • 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 Haematol 1986; 64: 309-317
    CrossrefPubMedGoogle Scholar
  • 3 Merton RE, Thomas DP. Experimental studies on the relative efficacy of dermatan sulphate and heparin as antithrombotic agents. Thromb Haemostas 1987; 58: 839-842
    PubMedGoogle Scholar
  • 4 Maggi A, Abbadini M, Pagella PG, Borowska A, Pangrazzi J, Donati MB. Antithrombotic properties of dermatan sulphate in a rat venous thrombosis model. Haemostasis 1987; 17: 329-335
    PubMedGoogle Scholar
  • 5 Thomas DP, Merton RE, Barrowcliffe TW. Relative efficacy of heparin and related glycosaminoglycans as antithrombotic drugs. Heparin and related polysaccharides. Ann NY Acad Sci 1989; 556: 313-320
    CrossrefPubMedGoogle Scholar
  • 6 Fernandez FA, Buchanan MR, Hirsh J, Fenton JW, Ofosu FA. Catalysis of thrombin inhibition provides an index for estimating antithrombotic potential of glycosaminoglycans in rabbits. Thromb Haemostas 1987; 57: 286-293
    PubMedGoogle Scholar
  • 7 Cadroy Y, Dol F, Caranobe C, Petitou M, Lormeau JC, Sié P, Choay J, Boneu B. Standard heparin enhances the antithrombotic activity of dermatan sulfate in the rabbit but CY 216 does not. Thromb Haemostas 1988; 59 (02) 295-298
    PubMedGoogle Scholar
  • 8 Johnson EA, Paterson MS. Lead precipitation: an aid to separation of dermatan and mucokeratan sulfates from glycosaminoglycan mixtures. Anal Biochem 1986; 158: 111-116
    CrossrefPubMedGoogle Scholar
  • 9 Eggleton CA, Barrowcliffe TW, Merton RE, Thomas DP. In vitro and in vivo studies of the anti-Xa activity of heparin. Thromb Res 1981; 34: 319-328
    PubMedGoogle Scholar
  • 10 Thomas DP, Merton RE. A low molecular weight heparin compared with unfractionated heparin. Thromb Res 1982; 28: 343-350
    CrossrefPubMedGoogle Scholar
  • 11 Wessler S, Reimer SM, Sheps MC. Biologic assay of a thrombosis inducing ability in human serum. J Appl Physiol 1959; 14: 943-946
    CrossrefPubMedGoogle Scholar
  • 12 Ofosu FA, Modi GJ, Smith LM, Cerskus AL, Hirsh J, Blajchman MA. Heparan sulfate and dermatan sulfate inhibit the generation of thrombin activity in plasma by complementary pathways. Blood 1984; 64: 727-747
    PubMedGoogle Scholar
  • 13 Ofosu FA, Buchanan MR, Anvari N, Smith LM, Blajchman MA. Plasma anticoagulant mechanisms of heparin, heparan sulfate, and dermatan sulfate. Heparin and Related Polysaccharides. Ann NY Acad Sci 1989; 556: 123-131
    CrossrefPubMedGoogle Scholar
  • 14 van Ryn-McKenna J, Ofosu FA, Gray E, Hirsh J, Buchanan MR. Effects of dermatan sulfate and heparin on inhibition of thrombus growth in vivo. In: Heparin and Related Polysaccharides. Ann NY Acad Sci 1989; 556: 304-312
    CrossrefPubMedGoogle Scholar
  • 15 Thomas DP, Merton RE, Gray E, Barrowcliffe TW. The relative antithrombotic effectiveness of heparin, a low molecular weight heparin, and a pentasaccharide fragment in an animal model. Thromb Haemostas 1989; 61: 204-207
    PubMedGoogle Scholar
  • 16 Dol F, Houin G, Rostin M, Mantastruc JL, Dupouy D, Gianese F, Sié F, Boneu B. Pharmacodynamics and pharmacokinetics of dermatan sulfate in humans. Blood 1989; 74: 1577-1582
    PubMedGoogle Scholar
  • 17 Dol F, Petitou M, Lormeau JC. et al Pharmacological properties of a low molecular weight dermatan sulfate: comparison with unfractionated dermatan sulfate. J Lab Clin Med 1990; 115: 43-51
    PubMedGoogle Scholar