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Effect of Dabigatran and Rivaroxaban on thrombomodulin mediated activation of protein C and thrombin activated fibrinolysis inhibitor (TAFI)
Author(s) -
Fareed Jawed,
Hoppensteadt Debra,
Cunanan Josephine,
Lewis Bruce
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.832.7
Subject(s) - rivaroxaban , dabigatran , thrombomodulin , thrombin , pharmacology , discovery and development of direct thrombin inhibitors , medicine , protein c , chemistry , anticoagulant , warfarin , atrial fibrillation , platelet
The new oral anticoagulant agents Dabigatran and Rivaroxaban target thrombin and factor Xa to mediate their anticoagulant effects perspectively. This study was designed to investigate the effects of active form Dabigatran and Rivaroxaban on the activation process of protein C and TAFI by thrombin‐thrombomodulin complex. Materials and Methods The active form of Dabigatran was synthesized. While Rivaroxaban was extracted from commercially available tablets. Both agents were dissolved in appropriate solution matrices at a stock concentration of 100ug/ml. Thrombin‐thrombomodulin mediated activation of protein C and TAFI were measured using specific chromogenic substrate based methods at a concentration of 0–10ug/ml in different matrices. Results Dabigatran produced a strong inhibition of the generation of both the activated protein C and TAFI (IC50<1.0ug/ml) whereas Rivaroxaban did not produce any inhibition of the activation of either of these proteases. Dabigatran also inhibited the amidolytic actions of thrombin‐thrombomodulin complex whereas Rivaroxaban did not produce any effect. Neither Dabigatran nor Rivaroxaban produced a direct inhibition of activated protein C or TAFI at concentrations of up to 10ug/ml. Conclusions The persistent inhibition of thrombin and its regulatory effects by Dabigatran may differentiate its pharmacologic profile from Rivaroxaban.