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Thromb Haemost 1996; 75(02): 286-291
DOI: 10.1055/s-0038-1650262
Original Article
Schattauer GmbH Stuttgart

Low Molecular Weight Heparin Is Responsible for the Anti-Xa Activity of Desmin 370

David Brieger
1   The Applied Research Group, The Heart Research Institute, Sydney, Australia
,
Joan Dawes
1   The Applied Research Group, The Heart Research Institute, Sydney, Australia
2   The CRC for Biopharmaceutical Research, Darlinghurst, NSW, Australia
› Author Affiliations
Further Information

Publication History

Received 07 June 1995

Accepted after resubmission 07 November 1995

Publication Date:
26 July 2018 (online)

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Summary

Dermatan sulphate does not catalyse the inactivation of factor Xa. However, the low molecular weight (LMW) dermatan sulphate Desmin 370 has been shown to generate circulating anti-Xa activity following administration to humans. Using a single batch of Desmin 370, we measured 3 U/mg of anti-Xa activity by amidolytic assay in vitro. The material responsible for this activity had a lower molecular weight range (6000 and 1800 Da) than Desmin 370 and was more highly sulphated than the bulk of the drug. Heparinase digestion of Desmin 370 eliminated 90% of the in vitro anti-Xa activity without significantly interfering with its ability to potentiate inactivation of thrombin by HCII, suggesting that the anti-Xa activity is not due to dermatan sulphate and is probably heparin. When 125I-labelled Desmin 370 together with 40 mg/kg carrier drug was administered intravenously to a rabbit, anti-Xa activity was readily detectable in the plasma for up to 10 h and had a longer half-life than the sulphated radiolabel. Most of this anticoagulant activity was recovered from the plasma by Polybrene affinity chromatography and was probably a sulphated glycosaminoglycan. Administration of the heparinase-digested drug to a rabbit resulted in 70% less anti-Xa activity than the undigested drug. We conclude that Desmin 370 contains detectable quantities of biologically active low molecular weight heparin, which is responsible for persistent anti-Xa activity following intravenous administration.

 

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