Antithrombotic Properties Of Low Molecular Weight Heparin Fractions From Porcine Mucosal Heparin

Abstract

A previous report from our laboratories has described the extraction and physicochemical properties of a low molecular weight fraction (mol wt 4-8 × 103 daltons) from porcine mucosal heparin (Choay et. al. thrombosis Res 18, 573, 1980). Beside exhibiting a strong anti Xa (>250 u/mg) activity, this product possessed strong antithrombotic properties in a modified rabbit stasis thrombosis model. At a 125 anti Xa u/kg it protected the thrombotic effects of activated prothrombin complex concentrate (20 u/kg) and Prothrombin Complex Concentrate/Russell’s Viper Venom challenge in both the pretreatment and post-treatment regiments. At 1250 anti Xa u/kg SC it also showed antithrombotic effects for various periods. We have also obtained another low molecular weight fraction from porcine mucosal heparin by controlled depolymerization with nitrous acid. This product possessed saccharides with molecular weight ranging 3-6 × 103 daltons and exhibited a specific activity of >200 anti Xa u/mg. At a 125 anti Xa u/kg this product also showed antithrombotic activity against the thrombotic effects of activated prothrombin complex concentrates, prothrombin complex concentrates and Russell’s Viper Venom. In contrast to these two low molecular weight fractions porcine mucosal heparin in identical anti Xa units failed to produce protection against the thrombogenic stimuli. Our studies suggest that low molecular weight heparin fractions with strong anti Xa and antithrombotic activities can be obtained by chemical depolymerization. Furthermore, their biologic properties are found to be similar to the naturally occuring low molecular weight fractions present in native porcine mucosal heparin.