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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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Effects of rivaroxaban and melagatran (0.001–0.3 mg kg−1 i.v.) on thrombin–antithrombin (TAT) complex (A, B), fibrinogen levels (C, D), and platelet counts (E, F) 10 minutes after injection of tissue factor (8 mg kg−1) in male rats. Results are mean ± standard error of the mean (n = 10). **P < 0.01, ***P < 0.001 vs. tissue factor control group; †P < 0.05, ††P < 0.01, †††P < 0.001 vs. sham control group. i.v., intravenous.
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fig05: Effects of rivaroxaban and melagatran (0.001–0.3 mg kg−1 i.v.) on thrombin–antithrombin (TAT) complex (A, B), fibrinogen levels (C, D), and platelet counts (E, F) 10 minutes after injection of tissue factor (8 mg kg−1) in male rats. Results are mean ± standard error of the mean (n = 10). **P < 0.01, ***P < 0.001 vs. tissue factor control group; †P < 0.05, ††P < 0.01, †††P < 0.001 vs. sham control group. i.v., intravenous.

Mentions: TF significantly increased TAT levels by 13-fold from 9 ± 5 to 116 ± 11 μg L−1 and from 7 ± 2 to 88 ± 10 μg L−1 in the control animals of the rivaroxaban and melagatran groups, respectively, within 10 minutes after injection, without affecting fibrinogen concentration or platelet count (Fig.5). There was a slight increase in APTT but not PT in the control animals (Table3).


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)

Effects of rivaroxaban and melagatran (0.001–0.3 mg kg−1 i.v.) on thrombin–antithrombin (TAT) complex (A, B), fibrinogen levels (C, D), and platelet counts (E, F) 10 minutes after injection of tissue factor (8 mg kg−1) in male rats. Results are mean ± standard error of the mean (n = 10). **P < 0.01, ***P < 0.001 vs. tissue factor control group; †P < 0.05, ††P < 0.01, †††P < 0.001 vs. sham control group. i.v., intravenous.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig05: Effects of rivaroxaban and melagatran (0.001–0.3 mg kg−1 i.v.) on thrombin–antithrombin (TAT) complex (A, B), fibrinogen levels (C, D), and platelet counts (E, F) 10 minutes after injection of tissue factor (8 mg kg−1) in male rats. Results are mean ± standard error of the mean (n = 10). **P < 0.01, ***P < 0.001 vs. tissue factor control group; †P < 0.05, ††P < 0.01, †††P < 0.001 vs. sham control group. i.v., intravenous.
Mentions: TF significantly increased TAT levels by 13-fold from 9 ± 5 to 116 ± 11 μg L−1 and from 7 ± 2 to 88 ± 10 μg L−1 in the control animals of the rivaroxaban and melagatran groups, respectively, within 10 minutes after injection, without affecting fibrinogen concentration or platelet count (Fig.5). There was a slight increase in APTT but not PT in the control animals (Table3).

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