Direct thrombin inhibitors, but not the direct factor Xa inhibitor rivaroxaban, increase tissue factor-induced hypercoagulability in vitro and in vivo.
Bottom Line: However, in the presence of rhs-TM, lower concentrations of melagatran (119-474 nmol L(-1) ) and dabigatran (68-545 nmol L(-1) ) enhanced endogenous thrombin potential, peak TG, and F1+2 formation in normal plasma but not in protein C-deficient plasma.In vivo, rivaroxaban dose-dependently inhibited TAT generation, whereas melagatran showed a paradoxical effect, with an increase in TAT and a small decrease in fibrinogen and platelet count at lower doses.In contrast, rivaroxaban reduced TG and hypercoagulability under all conditions studied, suggesting that it does not suppress this negative-feedback system.
Affiliation: Pharma R&D Discovery Research, Bayer Pharma AG, Wuppertal, Germany.Show MeSH
Related in: MedlinePlus
Mentions: Rivaroxaban significantly inhibited TG in a concentration-dependent manner in normal human PPP (Figs1A, 2A, and 3A,B), resulting in IC50 for Cmax of 44 ± 6 and 66 ± 5 nmol L−1 in the presence and absence of rhs-TM, respectively, and for ETP of 57 ± 8 and 697 ± 106 nmol L−1 in the presence and absence of rhs-TM, respectively (Table2).
Affiliation: Pharma R&D Discovery Research, Bayer Pharma AG, Wuppertal, Germany.