Structural basis for the anticoagulant activity of heparin. 1. Relationship to the number of charged groups

Publisher Website
Google Scholar
Abstract
Information concerning the chemical heterogeneity of heparins and the relationships between the anticoagulant activity (USP assay) and the anionic density of the heparin was studied. A sample of commercial heparin was fractionated into 13 fractions by sequential extraction in a 2-phase system of 1-butanol-aqueous NaCl containing excess hexadecylpyridinium chloride. The anionic density distribution was characterized by the fractional distribution of uronate among the fractions. The fractions were characterized by several molar ratios of constituents, MW, charge density and anticoagulant activity in recalcified sheep plasma. The heparin was broadly distributed among the last 10 fractions; the first 3 contained impurities which were completely separated from the heparin fractions. The heparin fractions differ systematically in anionic density but are of substantially the same MW. Anticoagulant activity increased markedly with anionic density, ranging from 81 units/mg for the heparin fraction with the lowest anionic density up to a high of 243 units/mg. The relationship between anticoagulant activity and anionic density or its square is nonlinear. In the latter case an initial linear relationship was seen for anticoagulant activities of less than 200 units/mg.

This publication has 1 reference indexed in Scilit: