title: Low molecular weight heparin is responsible for the anti-Xa activity of Desmin 370.
abstract: 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.
authors.affiliation: Applied Research Group, The Heart Research Institute, Sydney, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Brieger
authors.forename: J
authors.initials: J
authors.lastname: Dawes
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology*; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D003871:Dermatan Sulfate / Q000737:chemistry / Q000494:pharmacology*; D065427:Factor Xa Inhibitors; D005260:Female; D019763:Heparin Lyase; D006495:Heparin, Low-Molecular-Weight / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011817:Rabbits
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D003871:Dermatan Sulfate; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase