{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:33:44Z","timestamp":1790883224330,"version":"4.1.0"},"reference-count":37,"publisher":"Georg Thieme Verlag KG","issue":"04","funder":[{"DOI":"10.13039\/501100004271","name":"Sapienza Universit\u00e0 di Roma","doi-asserted-by":"crossref","award":["AR22419077BB6154,RG123188B4CD04C9"],"award-info":[{"award-number":["AR22419077BB6154,RG123188B4CD04C9"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"crossref","award":["Next Generation EU - PE8\u2014Project Age-It: \u201cAgei"],"award-info":[{"award-number":["Next Generation EU - PE8\u2014Project Age-It: \u201cAgei"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Atrial fibrillation (AF) is linked to an elevated risk of thromboembolic events. Despite the use of guideline-recommended direct anticoagulants (DOACs), a significant proportion of AF patients show a residual risk of thromboembolic events, driven by mechanisms that are not fully understood.<\/jats:p>\n                  <jats:p>We conducted a pilot study to characterize the platelet function in DOACs-treated AF patients, to explore whether an association between platelets and the residual thromboembolic risk exists.<\/jats:p>\n                  <jats:p>Within the Age-It project of the National Recovery and Resilience Plan, we examined by flow cytometry the platelet phenotype, reactivity, and mitochondrial function and quantified 12 inflammatory cytokines of individuals with DOACs-treated permanent AF without a history of stroke (n\u2009=\u200918, 66\u2009\u00b1\u200913 years, 39% females), compared with an age-, sex-, and comorbidity-matched control group without AF (n\u2009=\u200918, 65\u2009\u00b1\u200911 years, 39% females).<\/jats:p>\n                  <jats:p>Unstimulated circulating platelets of DOACs-treated AF displayed a low-adhesive phenotype compared with matched controls. Upon stimulation, platelets of DOACs-treated AF were hyporeactive to ADP and PAR1 stimulation, but hyper-reactive to GPVI stimulation (adjusted p\u2009&lt;\u20090.01). The lower responsiveness to ADP correlated with increased plasmatic concentrations of IFN-\u03b3 (r\u2009=\u2009\u2212\u20090.539; p\u2009&lt;\u20090.05) and TNF-\u03b1 (r\u2009=\u2009\u2212\u20090.472; p\u2009&lt;\u20090.05). The higher reactivity to GPVI associated with an increased mitochondrial function, which positively correlated with TNF-\u03b1 levels.<\/jats:p>\n                  <jats:p>Individuals with AF treated with DOACs exhibit low-grade inflammation and an altered platelet reactivity, suggesting a potential mechanism behind their residual thromboembolic risk. Further well-powered studies are warranted to test whether the observed platelet phenotype is implicated with the residual thromboembolic events in DOACs-treated AF patients.<\/jats:p>","DOI":"10.1055\/a-2632-3100","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T19:35:17Z","timestamp":1749670517000},"page":"371-382","source":"Crossref","is-referenced-by-count":1,"title":["Distinct Platelet Phenotype and Reactivity in Individuals with Permanent Atrial Fibrillation Treated with Direct Oral Anticoagulants: A Pilot Study"],"prefix":"10.1055","volume":"126","author":[{"given":"Marzia","family":"Miglionico","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Maiorca","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Sabetta","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"D'amico","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Cincione","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Buoninfante","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marin","family":"Pecani","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Proietti","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy"},{"name":"Division of Subacute Care, IRCCS Istituti Clinici Scientifici Maugeri, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3788-8942","authenticated-orcid":false,"given":"Giulio Francesco","family":"Romiti","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"},{"name":"Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Cangemi","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Basili","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Raparelli","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Stefanini","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"},{"name":"Istituto Pasteur Italia - Fondazione Cenci-Bolognetti, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"issue":"06","key":"ref1","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41569-022-00820-8","article-title":"Epidemiology and modifiable risk factors for atrial fibrillation","volume":"20","author":"A D Elliott","year":"2023","journal-title":"Nat Rev Cardiol"},{"issue":"03","key":"ref2","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1161\/STROKEAHA.115.012004","article-title":"Atrial fibrillation and mechanisms of stroke: time for a new 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