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Effect of the FXa inhibitors Rivaroxaban and Apixaban on platelet activation in patients with atrial fibrillation

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Abstract

Rivaroxaban and Apixaban, increasingly used for stroke prevention in non-valvular atrial fibrillation (AF), might impact platelet reactivity directly or indirectly. By inhibition of Factor Xa (FXa) they preclude not only generation of relevant thrombin amounts but also block signalling of FXa via protease activated receptors. However, weather FXa-inhibition affects platelet haemostasis remains incompletely known. One hundred and twenty-eight patients with AF on chronic anticoagulation with either Rivaroxaban or Apixaban for at least 4 weeks were included in the study. In a time course group (25 on Rivaroxaban, 13 on Apixaban) venous blood samples were taken before NOAC medication intake in the morning as well as 2 and 6 h afterwards. In 90 patients (Rivaroxaban n = 73, Apixaban n = 17) blood samples were drawn during left atrial RFA procedures before as well as 10 and 60 min after the first heparin application (RFA group). Platelet reactivity analyzed by whole blood aggregometry (Multiplate Analyzer, Roche) in response to ADP, Collagen, TRAP and ASPI (arachidonic acid) was not altered by Rivaroxaban or Apixaban neither in the time course nor in the RFA group. Moreover, soluble P-selectin, Thrombospondin, von Willebrand Factor and beta thromboglobulin plasma levels, measured by ELISA, showed no statistically significant changes in both clinical settings for either FXa-inhibitor. The present study fails to demonstrate any significant changes on platelet reactivity in patients with AF under chronic Rivaroxaban or Apixaban medication, neither for trough or peak levels nor in case of a haemostatic activation in vivo as depicted by RFA procedures.

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Authors and Affiliations

  1. Deutsches Herzzentrum der Technischen Universität München, Lazarettstr 36, 80636, Munich, Germany

    B. Steppich, F. Dobler, L. C. Brendel, G. Hessling, S. L. Braun, A. L. Steinsiek, I. Deisenhofer & I. Ott

  2. Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands

    A. Hyseni & M. Roest

Authors
  1. B. Steppich
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  2. F. Dobler
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  3. L. C. Brendel
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  4. G. Hessling
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  5. S. L. Braun
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  6. A. L. Steinsiek
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  7. I. Deisenhofer
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  8. A. Hyseni
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  9. M. Roest
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  10. I. Ott
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Correspondence to I. Ott.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Steppich, B., Dobler, F., Brendel, L.C. et al. Effect of the FXa inhibitors Rivaroxaban and Apixaban on platelet activation in patients with atrial fibrillation. J Thromb Thrombolysis 43, 490–497 (2017). https://doi.org/10.1007/s11239-017-1495-z

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