Thromb Haemost 1982; 47(03): 244-248
DOI: 10.1055/s-0038-1657178
Original Article
Schattauer GmbH Stuttgart

Effects of Heparin Oligosaccharides with High Affinity for Antithrombin III in Experimental Venous Thrombosis

D P Thomas
The Division of Blood Products, National Institute for Biological Standards and Control, London, England
,
Rosemary E Merton
The Division of Blood Products, National Institute for Biological Standards and Control, London, England
,
T W Barrowcliffe
The Division of Blood Products, National Institute for Biological Standards and Control, London, England
,
L Thunberg
*   The Department of Medical and Physiological Chemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden
,
U Lindahl
*   The Department of Medical and Physiological Chemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden
› Author Affiliations
Further Information

Publication History

Received 08 March 1982

Accepted 06 April 1982

Publication Date:
13 July 2018 (online)

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Summary

The in vitro and in vivo characteristics of two oligosaccharide heparin fragments have been compared to those of unfractionated mucosal heparin. A decasaccharide fragment had essentially no activity by APTT or calcium thrombin time assays in vitro, but possessed very high specific activity by anti-Factor Xa assays. When injected into rabbits at doses of up to 80 ¼g/kg, this fragment was relatively ineffective in impairing stasis thrombosis despite producing high blood levels by anti-Xa assays. A 16-18 monosaccharide fragment had even higher specific activity (almost 2000 iu/mg) by chromogenic substrate anti-Xa assay, with minimal activity by APTT. When injected in vivo, this fragment gave low blood levels by APTT, very high anti-Xa levels, and was more effective in preventing thrombosis than the decasaccharide fragment. However, in comparison with unfractionated heparin, the 16-18 monosaccharide fragment was only partially effective in preventing thrombosis, despite producing much higher blood levels by anti-Xa assays.

It is concluded that the high-affinity binding of a heparin fragment to antithrombin III does not by itself impair venous thrombogenesis, and that the anti-Factor Xa activity of heparin is only a partial expression of its therapeutic potential.