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1: Eur J Pharmacol. 2000 Mar 10;391(1-2):1-9.
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Inhibition of antithrombin by protein SV-IV normalizes the coagulation of hemophilic blood.

Di Micco B, Caen J, Colonna G, Macalello MA, Marchese M, Stiuso P, Di Micco P, Morelli F, Metafora S.

Department of Biochemistry and Biophysics, II University of Naples, 80138, Naples, Italy.

The aim of the study was to evaluate the effect of the protein Seminal Vesicle Protein No. 4 (SV-IV), a potent inhibitor of antithrombin III (antithrombin), on the coagulation of blood obtained from patients affected by hemophilia A. In the coagulating blood of these patients, the antithrombin/thrombin ratio was found to be markedly higher (about 44) than in normal individuals (about 4. 4). This high ratio was related to the low efficiency of thrombin-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 and hemophilic plasma). The elevated concentration of free antithrombin in hemophiliacs was primarily a consequence of a reduced consumption caused by the 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 serum antithrombin and thrombin-antithrombin complexes, normalizing, as a consequence, the clotting time and other coagulation parameters. Similar results were obtained by using appropriate concentration of factor VIII.

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PMID: 10720629 [PubMed - indexed for MEDLINE]