A peptide derivative (1-70 fragment) of protein SV-IV accelerates human blood coagulation in vitro by selective inhibition of the heparin-induced antithrombin III activation process

The effect of two peptide derivatives of the rat SV-TV (SV-IV/A: 1-70 fragment; SV-IV/B: 71-90 fragment) on human blood coagulation was investigated. The SV-IV/A fragment was found lit possess the same procoagulant activity of the native protein, whereas SV-IV/B retained only a very small fraction of the activity. The results obtained strongly suggest that the procoagulant activity of SV-IV/A is due, like SV-TV, to a selective inhibition of the antithrombin III (AT III) activation process induced by heparin, an essential cofactor of ATIII. The main data supporting this hypothesis are the following: 1) the concentration of active serum ATIII decreases when SV-IV/A is present in the clotting system; 2) the plasma treatment with SV-IV/A reduces the concentration of AT III, but not that of other plasma serine protease inhibitors; 3) the recalcification time (RT) of the plasma treated with a rabbit anti-AT III polyclonal antiserum is not modified by SV-IV/A; 4) the presence of SV-IV/A in a reaction mixture containing pure fibrinogen, alpha-thrombin, heparin, and AT III neutralizes the thrombin inhibition induced by AT III; 5) the concentration of the thrombin-AT III complexes, occurring in sera obtained from CaCl2-coagulated plasma, is markedly reduced in the presence of SV-IV/A; 6) appropriate concentrations of heparin neutralize the inhibitory effect of either SV-IV/A or SV-IV on the AT III activity iii vitro. (C) Munksgaard 1997.