A specific inhibitor of factor Xa, DX-9065a, exerts effective protection against experimental tumor induced disseminated intravascular coagulation in rats.
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| Abstract |
(+)-2S-2-[4-[[(35S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-[7- amidino-2-napthyl]propanoic acid hydrochloride pentahydrate (DX-9065a) is an antithrombin III-independent, selective inhibitor of activated blood coagulation factor X (FXa). We investigated the protective effects of DX-9065a against tumor-bearing experimental disseminated intravascular coagulation (DIC) induced by the inoculation of AH-109A cells into rats. DX-9065a was subcutaneously administered at doses of 0.03 and 0.1 mg/kg/hour through an osmotic pump transplanted immediately after the inoculation of the tumor cells during the observation period. Platelet count decreased 12 days after the inoculation, concomitant with an increase in the thrombin-antithrombin III complex and fibrin and fibrinogen degradation products. Doses of 0.03 and 0.1 mg/kg/hour of DX-9065a significantly inhibited the decrease in plasma fibrinogen concentration and platelet count 13 days after the inoculation, respectively. These findings suggest that direct, selective inhibition of FXa by DX-9065a improves the hypercoagulable state induced by the progress of solid tumor.
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| Authors | K Tanabe, Y Terada, T Shibutani, S Kunitada, T Kondo |
| Journal | Thrombosis research (Thromb Res) Vol. 96 Issue 2 Pg. 135-43 (Oct 15 1999) ISSN: 0049-3848 [Print] United States |
| PMID | 10574591 (Publication Type: Journal Article) |
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