LOW-MOLECULAR-WEIGHT HEPARIN IS RESPONSIBLE FOR THE ANTI-XA ACTIVITY OF DESMIN-370

Dermatan sulphate does not catalyse the inactivation of factor Xa. How ever, the low molecular weight (LMW) dermatan sulphate Desmin 370 has been shown to generate circulating anti-Xa activity following administ ration 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 resp onsible for this activity had a lower molecular weight range (6000 and 1800 Dal 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 a bility to potentiate inactivation of thrombin by HCII, suggesting that the anti-Xa activity is not due to dermatan sulphate and is probably heparin. When I-125-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. h lost of this anticoagulant acti vity was recovered from the plasma by Polybrene affinity chromatograph y and was probably a sulphated glycosaminoglycan. Administration of th e heparinase-digested drug to a rabbit resulted in 70% less anti-Xa ac tivity than the undigested drug. We conclude that Desmin 370 contains detectable quantities of biologically active low molecular weight hepa rin, which is responsible for persistent anti-Xa activity following in travenous administration.