Inhibition of thrombin-induced feedback activation of factor V:: a potential pathway for inhibition of thrombin generation by melagatran

被引：12

作者：

Boström, SL ^{[1
]}

Dagnelid, E ^{[1
]}

Hansson, GFH ^{[1
]}

Ulvinge, JC ^{[1
]}

机构：

[1] AstraZeneca R&D, Cell Biol & Biochem, S-431 Molndal, Sweden

来源：

BLOOD COAGULATION & FIBRINOLYSIS | 2004年 / 15卷 / 01期

关键词：

melagatran; ximelagatran; direct thrombin inhibitor; thrombin generation; factor V;

D O I：

10.1097/00001721-200401000-00005

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The feedback mechanism by which melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, inhibits thrombin generation was investigated in vitro, using an endogenous thrombin potential (ETP) assay. Melagatran decreased ETP in a concentration-dependent manner and increased the time to thrombin peak. FEIBA reversed the melagatran-induced reduction in ETP in a concentration-dependent manner and marginally reduced the prolongation of the time to thrombin peak. Similar results were observed for prothrombin as were seen with FEIBA. Both activated factor V and Russell's Viper Venomfactor V activator reversed the melagatran-induced prolongation in time to thrombin peak in a concentration-dependent manner and partially restored ETP. Prothrombin, in combination with Russell's Viper Venomfactor V or activated factor V, reversed both the melagatran-induced reduction in ETP and the prolongation in time to thrombin peak, in a concentration-dependent manner. These results indicate that inhibition of thrombin-mediated amplification reactions in blood coagulation is an effective way to delay or inhibit thrombin generation. (C) 2004 Lippincott Williams Wilkins.

引用

页码：25 / 30

页数：6

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