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Thromb Haemost 1981; 45(03): 214-218
DOI: 10.1055/s-0038-1650173
Original Article
Schattauer GmbH Stuttgart

Studies in Man and Experimental Animals of a Low Molecular Weight Heparin Fraction

D P Thomas
The National Institute for Biological Standards and Control, Holly Hill, London
,
R E Merton
*   The Glaxo Operations U. K. Limited, Westfield Road, Runcorn, Cheshire, U. K.
,
W E Lewis
The National Institute for Biological Standards and Control, Holly Hill, London
,
T W Barrowcliffe
The National Institute for Biological Standards and Control, Holly Hill, London
› Author Affiliations
Further Information

Publication History

Received 12 December 1980

Accepted 16 March 1981

Publication Date:
06 July 2018 (online)

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Summary

In vitro and in vivo studies were carried out on a commercially prepared low molecular weight heparin fraction. By APTT assay the fraction had a specific activity of half that of unfractionated mucosal heparin, yet retained full potency by anti-Xa assay (both clotting and chromogenic substrate). When administered intravenously to human volunteers, the anti-Xa/APTT ratio remained the same as it was in vitro. However, after subcutaneous injection, the ratio increased and anti-Xa activity could not be fully neutralized ex vivo by PF4. The fraction was as effective as unfractionated heparin in preventing experimental serum-induced thrombosis, suggesting that a heparin fraction with high specific activity by anti-Factor Xa assay compared to APTT activity may be an effective drug for the prophylaxis of venous thrombosis.

Keywords

Heparin - Heparin fraction - Experimental venous thrombosis
 

  • References

  • 1 Thomas DP. Heparin in the prophylaxis and treatment of venous thromboembolism. Sem Hematol 1978; 15: 01-17
    PubMedGoogle Scholar
  • 2 Salzman EW, Deykin D, Shapiro RM, Rosenberg RD. Management of heparin therapy – controlled prospective trial. New Engl J Med 1975; 292: 1046-1051
    CrossrefPubMedGoogle Scholar
  • 3 Mant MJ, Thong KL, Birtwhistle RV, O’Brien BD. Haemorrhagic complications of heparin therapy. Lancet 1977; 01: 1133-1135
    PubMedGoogle Scholar
  • 4 Lane DA, MacGregor IR, Michalski R, Kakkar VV. Anticoagulant activities of four unfractionated and fractionated heparins. Thromb Res 1978; 12: 257-271
    CrossrefPubMedGoogle Scholar
  • 5 Thomas DP, Barrowcliffe TW, Johnson EA. The influence of tissue source, salt and molecular weight on heparin activity. In: Clinical Usage of Heparin: Present and Future Trends. 1980 Verstraete M, Machin SE. Eds Scand J Haematol. Suppl 36 25. 40-49
    Google Scholar
  • 6 Johnson EA, Mulloy B. The molecular weight range of mucosal heparin preparations. Carbohydrate Res 1976; 51: 119-127
    CrossrefPubMedGoogle Scholar
  • 7 Andersson LO, Barrowcliffe TW, Holmer E, Johnson EA, Sims GEC. Anticoagulant properties of heparin fractionated by affinity chromatography on matrix bound antithrombin III and by gel filtration. Thromb Res 1976; 9: 575-583
    CrossrefPubMedGoogle Scholar
  • 8 Denson KWE, Bonnar K. The measurement of heparin. A method based on the potentiation of anti-Factor Xa. Thromb Diath Haemorrh 1973; 30: 471-479
    PubMedGoogle Scholar
  • 9 Kirkwood TBL, Snape TJ. Biometric principles in clotting and clot lysis assays. Clin Lab Haematol 1980; 02: 155-167
    CrossrefPubMedGoogle Scholar
  • 10 Levine SP, Wohl H. Human platelet factor 4: purification and characterization by affinity chromatography. Purification of human platelet factor 4. J Biol Chem 1976; 251: 324-328
    PubMedGoogle Scholar
  • 11 Wessler S, Reiner L, Freiman DG, Reimer SM, Lertzman M. Serum-induced thrombosis. Studies of its induction and evolution under controlled conditions in vivo. Circulation 1959; 20: 864-874
    CrossrefPubMedGoogle Scholar
  • 12 Barrowcliffe TW, Johnson EA, Eggleton CA, Kemball-Cook G, Thomas DP. Anticoagulant activities of high and low molecular weight heparin fraction. Brit J Haematol 1979; 41: 573-583
    CrossrefPubMedGoogle Scholar
  • 13 Holmer E, Lindahl U, Bäckström G, Thunberg L, Sandberg H, Söderström G, Andersson LO. Anticoagulant activities and effects on platelets of a heparin fragment with a high affinity for antithrombin. Thromb Res 1980; 18: 861-869
    CrossrefPubMedGoogle Scholar
  • 14 Andersson LO, Barrowcliffe TW, Holmer E, Johnson EA, Söderström E. Molecular weight dependency of the heparin potentiated inhibition of thrombin and activated Factor X. Effect of heparin neutralization in plasma. Thromb Res 1979; 15: 531-541
    CrossrefPubMedGoogle Scholar
  • 15 Thomas DP, Barrowcliffe TW, Merton RE, Stocks J, Dawes J, Pepper DS. In vivo release of anti-Xa clotting activity by a heparin analogue. Thromb Res 1980; 17: 831-840
    CrossrefPubMedGoogle Scholar
  • 16 Wessler S. Thrombosis in the presence of vascular stasis. Amer J Med 1962; 33: 648-666
    CrossrefPubMedGoogle Scholar
  • 17 De ClerckF, Goosens J, Vermylen J, Hornstra G, Reneman RS. Modification of venous stasis thrombosis in the rat by platelet-active drugs and by heparin. Arch int Pharmacodyn 1976; 222: 233-242
    PubMedGoogle Scholar
  • 18 Gitel SN, Stephenson RC, Wessler S. In vitro and in vivo correlation of clotting protease activity: effect of heparin. Proc Natl Acad Sci USA 1977; 74: 3028-3032
    CrossrefPubMedGoogle Scholar
  • 19 Negus D, Friedgood A, Derby S, Avery A, Wells BW. Ultra-low dose heparin in the prevention of post-operative deep vein thrombosis. Lancet 1980; 01: 891-894
    PubMedGoogle Scholar
  • 20 Wessler S, Gitel S. Control of heparin therapy. Prog Haemos Thrombos 1976; 03: 311-329
    PubMedGoogle Scholar