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Direct thrombin inhibitors, but not the direct factor Xa inhibitor rivaroxaban, increase tissue factor-induced hypercoagulability in vitro and in vivo.

Perzborn E, Heitmeier S, Buetehorn U, Laux V - J. Thromb. Haemost. (2014)

Bottom Line: In the absence of rhs-TM, melagatran and dabigatran also inhibited TG concentration dependently.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.

View Article: PubMed Central - PubMed

Affiliation: Pharma R&D Discovery Research, Bayer Pharma AG, Wuppertal, Germany.

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Related in: MedlinePlus

Peak thrombin generation (Cmax) and endogenous thrombin potential (ETP) in normal human platelet-poor plasma spiked with rivaroxaban (n = 9), melagatran (n = 8), or dabigatran (n = 12) in the absence and presence of recombinant human soluble thrombomodulin (rhs-TM; 10 nmol L−1). Results are shown as mean ± standard error of the mean. *P < 0.05, **P < 0.01, ***P < 0.001 vs. respective controls.
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fig03: Peak thrombin generation (Cmax) and endogenous thrombin potential (ETP) in normal human platelet-poor plasma spiked with rivaroxaban (n = 9), melagatran (n = 8), or dabigatran (n = 12) in the absence and presence of recombinant human soluble thrombomodulin (rhs-TM; 10 nmol L−1). Results are shown as mean ± standard error of the mean. *P < 0.05, **P < 0.01, ***P < 0.001 vs. respective controls.

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).


Direct thrombin inhibitors, but not the direct factor Xa inhibitor rivaroxaban, increase tissue factor-induced hypercoagulability in vitro and in vivo.

Perzborn E, Heitmeier S, Buetehorn U, Laux V - J. Thromb. Haemost. (2014)

Peak thrombin generation (Cmax) and endogenous thrombin potential (ETP) in normal human platelet-poor plasma spiked with rivaroxaban (n = 9), melagatran (n = 8), or dabigatran (n = 12) in the absence and presence of recombinant human soluble thrombomodulin (rhs-TM; 10 nmol L−1). Results are shown as mean ± standard error of the mean. *P < 0.05, **P < 0.01, ***P < 0.001 vs. respective controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4285304&req=5

fig03: Peak thrombin generation (Cmax) and endogenous thrombin potential (ETP) in normal human platelet-poor plasma spiked with rivaroxaban (n = 9), melagatran (n = 8), or dabigatran (n = 12) in the absence and presence of recombinant human soluble thrombomodulin (rhs-TM; 10 nmol L−1). Results are shown as mean ± standard error of the mean. *P < 0.05, **P < 0.01, ***P < 0.001 vs. respective controls.
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).

Bottom Line: In the absence of rhs-TM, melagatran and dabigatran also inhibited TG concentration dependently.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.

View Article: PubMed Central - PubMed

Affiliation: Pharma R&D Discovery Research, Bayer Pharma AG, Wuppertal, Germany.

Show MeSH
Related in: MedlinePlus