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Ex-vivo antiplatelet effects of oral anticoagulants
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  • Giulia Renda,
  • Valentina Bucciarelli,
  • Giulia Barbieri,
  • Paola Lanuti,
  • Martina Berteotti,
  • Gelsomina Malatesta,
  • Francesca Cesari,
  • Tanya Salvatore,
  • Betti Giusti,
  • Anna Maria Gori,
  • Rossella Marcucci,
  • Raffaele De Caterina
Giulia Renda
Gabriele d'Annunzio University of Chieti and Pescara Department of Sciences
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Valentina Bucciarelli
Gabriele d'Annunzio University of Chieti and Pescara Department of Sciences
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Giulia Barbieri
University of Florence
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Paola Lanuti
Gabriele d'Annunzio University of Chieti and Pescara Department of Sciences
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Martina Berteotti
University of Florence
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Gelsomina Malatesta
Gabriele d'Annunzio University of Chieti and Pescara Department of Sciences
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Francesca Cesari
University of Florence
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Tanya Salvatore
Gabriele d'Annunzio University of Chieti and Pescara Department of Sciences
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Betti Giusti
University of Florence
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Anna Maria Gori
University of Florence
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Rossella Marcucci
University of Florence
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Raffaele De Caterina
University of Pisa

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Abstract

Background: The impact of non-vitamin K antagonist oral anticoagulants (NOACs) on platelet function is still unclear. We conducted a comprehensive ex-vivo study aimed at assessing the effect of the four currently marketed NOACs on platelet function. Methods: We incubated blood samples from healthy donors with concentrations of NOACs (50, 150 and 250 ng/mL), in the range of those achieved in the plasma of patients during therapy. We evaluated: generation of thrombin; light transmittance platelet aggregation (LTA) in response to adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), human γ-thrombin (THR) and tissue factor (TF); generation of thromboxane (TX)B2; expression of protease-activated receptor (PAR)-1 and P-selectin on the platelet surface. Results: All NOACs concentration-dependently reduced thrombin generation compared with control. THR-induced LTA was suppressed by the addition of dabigatran at any concentration, while TF-induced LTA was reduced by factor-Xa inhibitors. ADP- and TRAP-induced LTA was not modified by NOACs. TXB2 generation was reduced by dabigatran, rivaroxaban and apixaban compared with control, particularly at the highest concentrations, but not by edoxaban. We found a concentration-dependent increase of PAR-1 expression after incubation with dabigatran, particularly at the highest concentrations, but not with FXa inhibitors; P-selectin expression was not changed by any drugs. Conclusions: Treatment with the NOACs is associated with measurable ex-vivo changes in platelet function, arguing for antiplatelet effects beyond the well-known anticoagulant activities of these drugs. There are differences, however, among the NOACs, and especially between dabigatran and the FXa inhibitors.