ANTITHROMBIN-MEDIATED INHIBITION OF FACTOR VIIA-TISSUE FACTOR COMPLEXBY THE SYNTHETIC PENTASACCHARIDE REPRESENTING THE HEPARIN-BINDING SITE TO ANTITHROMBIN

We examined the effect of the synthetic pentasaccharide representing t he minimal binding site of heparin to antithrombin on the antithrombin -mediated inactivation of factor VIIa bound to tissue factor. This eff ect was compared to the effect of unfractionated heparin. Using purifi ed recombinant human coagulation factors and either a clotting or an a midolytic assay for the determination of the residual activity of fact or VIIa, we showed that the pentasaccharide was an efficient antithrom bin-dependent inhibitor of the coagulant activity of tissue factor-fac tor VIIa complex. In our experimental conditions, assuming a mean MW o f 14,000 for heparin, the molar pseudo-first order rate constants for ATIII-mediated FVIIa inhibition by ATIII-binding heparin and by the sy nthetic pentasaccharide were found to be similar with respective value s of 104,000 +/- 10,500 min(-1) and 112,000 +/- 12,000 min(-1) (mean /- s.e.m., n = 3).