Inhibition of antithrombin by protein SV-IV normalizes the coagulation of hemophilic blood

The aim of the study was to evaluate the effect of the protein Seminal Vesi cle protein No. 4 (SV-IV), a potent inhibitor of antithrombin III (antithro mbin), on the coagulation of blood obtained from patients affected by hemop hilia A. In the coagulating blood of these patients, the antithrombin/throm bin ratio was found to be markedly higher (about 44) than in normal individ uals (about 4.4). This high ratio was related to the low efficiency of thro mbin-generating reactions induced by the factor VIII deficiency and to the high levels of free (not bound to serine proteases) antithrombin present in the hemophilic serum (antithrombin concentration was the same in normal an d hemophilic plasma). The elevated concentration of free antithrombin in he mophiliacs was primarily a consequence of a reduced consumption caused by t he scarce availability in the hemophilic serum of factors Xa and IIa, which are serine proteases possessing strong binding affinity for antithrombin. Addition of SV-IV to coagulating hemophilic blood reduced markedly the seru m antithrombin and thrombin-antithrombin complexes, normalizing, as a conse quence, the clotting time and other coagulation parameters. Similar results were obtained by using appropriate concentration of factor VIII. (C) 2000 Published by Elsevier Science B.V. All rights reserved.