{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:08:00Z","timestamp":1791904080759,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T00:00:00Z","timestamp":1711843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Boehringer Ingelheim (Ingelheim am Rhein, Germany)"},{"name":"Bayer AG (Wuppertal, Germany)"},{"name":"Bristol Myers Squibb Company (New Brunswick, NJ, USA)"},{"name":"Daiichi Sankyo (Ch\u016b\u014d, Tokyo, Japan)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>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 \u03b3-thrombin (THR) and tissue factor (TF); generation of thromboxane (TX)B2; and 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 all NOACs, particularly at the highest concentrations. We found a concentration-dependent increase in PAR-1 expression after incubation with dabigatran, mainly 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, especially between dabigatran and the FXa inhibitors.<\/jats:p>","DOI":"10.3390\/jcdd11040111","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:28:00Z","timestamp":1711891680000},"page":"111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ex Vivo Antiplatelet Effects of Oral Anticoagulants"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-8386","authenticated-orcid":false,"given":"Giulia","family":"Renda","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences and Center for Advanced Studies and Technology, G. d\u2019Annunzio University Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7003-6194","authenticated-orcid":false,"given":"Valentina","family":"Bucciarelli","sequence":"additional","affiliation":[{"name":"Cardiovascular Sciences Department, Azienda Ospedaliero-Universitaria delle Marche, 60121 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4197-9780","authenticated-orcid":false,"given":"Paola","family":"Lanuti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Aging Sciences and Center for Advanced Studies and Technology, G. d\u2019Annunzio University Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8281-4734","authenticated-orcid":false,"given":"Martina","family":"Berteotti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gelsomina","family":"Malatesta","sequence":"additional","affiliation":[{"name":"Cardiology Unit, National Institute of Health and Science on Aging (INRCA), 64125 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Cesari","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Salvatore","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences and Center for Advanced Studies and Technology, G. d\u2019Annunzio University Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8708-9444","authenticated-orcid":false,"given":"Betti","family":"Giusti","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Gori","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Marcucci","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1637-574X","authenticated-orcid":false,"given":"Raffaele","family":"De Caterina","sequence":"additional","affiliation":[{"name":"Cardiology Division 1-Pisa University Hospital, University of Pisa, 56124 Pisa, Italy"},{"name":"Fondazione Villa Serena per la Ricerca, 37011 Citt\u00e0 Sant\u2019Angelo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/35025229","article-title":"Thrombin signalling and protease-activated receptors","volume":"407","author":"Coughlin","year":"2000","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1159\/000073849","article-title":"Effects of the oral direct thrombin inhibitor ximelagatran on p-selectin expression and thrombin generation in atrial fibrillation","volume":"33","author":"Wolzt","year":"2003","journal-title":"Pathophysiol. 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