INFLUENCE OF VARIATIONS IN THE CHEMICAL-STRUCTURE OF HEPARIN ON ITS ANTI-COAGULANT AND ANTI-FACTOR XA ACTIVITIES

Fractions of hog mucosal heparin, distinguished by large differences in chemical composition, varied widely in anticoagulant activity and in their ability to potentiate the inhibition of Factor Xa. Anticoagulant activity was highest for fractions that consisted mainly of L-iduronic acid 2-sulfate and 2-deoxy-2-sulfamino-D-glucose 6-sulfate and decreased overall by a factor of 3 (from 145 to 56 USP units) as the proportion of residues of 2-acetamido-2-deoxy-D-glucose, D-glucuronic acid and L-iduronic acid became progressively more prominent. Conversely, a 10-fold increment in anti-Xa activity (from 59-639 U/mg) accompanied increases in the proportions of the minor, non-sulfated, heparin constituents. Individual steps of the coagulation process apparently are subject to selective catalytic effects on reaction rate by differently constituted molecules within a heparin preparation.