Role of heparin in the inactivation of thrombin, factor Xa, and plasmin by antithrombin III

To characterize the mode of action of heparin, the kinetic behaviour of the inhibition of thrombin, factor Xa, and plasmin by antithrombin III was studied in the presence and absence of heparin. Following the concentration dependence of inactivation, in both cases a linear dependence of the apparent first-order inactivation rate constant on the antithrombin III concentration was found. These results are explained by enzyme-heparin interactions. Thus, heparin is believed to act as an activator of the enzymes that makes them more susceptible to antithrombin III.

Values of kinetic constants for the inactivation reaction of the several enzymes were determined. From these values it is concluded that heparin influences primarily the thrombin-antithrombin III interaction.