EFFECT OF HEPARIN ON THE INACTIVATION RATE OF HUMAN FACTOR-XIA BY ANTITHROMBIN-III

  • 1 January 1982
    • journal article
    • research article
    • Vol. 60  (4) , 940-947
Abstract
Factor XIa catalyzes an important reaction in the early phase of blood coagulation by converting factor Ix to an active enzyme (factor IXa). Although antithrombin-III, an inhibitor of factor XIa, normally accounts for only 1/6 of the plasma inhibitory activity against factor XIa, its effectiveness is enhanced by heparin. The ability of heparin to potentiate factor XIa inhibition by both purified antithromin-III and plasma was studied using synthetic tripeptide amide substrates as well as a coagulant assay. No increase in the inactivation rate of factor XIa amidolytic activity by purified antithrombin-III was observed in the presence of therapeutic heparin concentrations (1 U/ml), although inhibition of the amidolytic activity of thormbin by purified antithrombin-III was enhanced at least 20-fold by the same concentration of heparin. Despite the ability of heparin (1 U/ml) to increase the inactivation rate of thrombin by plasma, no acceleration of the rate of inhibition of factor XIa by plasma was observed. Similar results were found when the inhibition of factor XIa was monitored with a coagulant assay after first removing the heparin. Only at heparin concentrations of 5 and 10 U/ml, was a 2- and 4-fold increase in the inactivation rate of factor XIa by purified antithrombin III observed. In both purified systems as well as plasma, heparin, at concentrations observed in clinical practice, does not accelerate the inactivation rate of human factor XIa by antithrombin-III.