Distinct Platelet Phenotype and Reactivity in Individuals with Permanent Atrial Fibrillation Treated with Direct Oral Anticoagulants: A Pilot Study

Marzia Miglionico; Francesca Maiorca; Annamaria Sabetta; Ludovica Lombardi; Tania D'amico; Alessandro Cincione; Giovanni Buoninfante; Marin Pecani; Marco Proietti; Giulio Francesco Romiti; Roberto Cangemi; Stefania Basili; Valeria Raparelli; Lucia Stefanini

doi:10.1055/a-2632-3100

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost
DOI: 10.1055/a-2632-3100

Cellular Haemostasis and Platelets

Distinct Platelet Phenotype and Reactivity in Individuals with Permanent Atrial Fibrillation Treated with Direct Oral Anticoagulants: A Pilot Study

Marzia Miglionico^*

¹Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

,

Francesca Maiorca^*

²Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

,

Annamaria Sabetta

²Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

,

Ludovica Lombardi

²Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

,

Tania D'amico

¹Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

,

Alessandro Cincione

²Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

,

Giovanni Buoninfante

²Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

,

Marin Pecani

¹Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

,

Marco Proietti

³Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

⁴Division of Subacute Care, IRCCS Istituti Clinici Scientifici Maugeri, Milan, Italy

,

Giulio Francesco Romiti

²Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

⁵Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom

,

Roberto Cangemi

²Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

,

Stefania Basili

²Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

,

Valeria Raparelli

²Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

,

Lucia Stefanini

²Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

⁶Istituto Pasteur Italia - Fondazione Cenci-Bolognetti, Rome, Italy

› Institutsangaben

Abstract

Background

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.

Objective

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.

Methods

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 = 18, 66 ± 13 years, 39% females), compared with an age-, sex-, and comorbidity-matched control group without AF (n = 18, 65 ± 11 years, 39% females).

Results

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 < 0.01). The lower responsiveness to ADP correlated with increased plasmatic concentrations of IFN-γ (r = − 0.539; p < 0.05) and TNF-α (r = − 0.472; p < 0.05). The higher reactivity to GPVI associated with an increased mitochondrial function, which positively correlated with TNF-α levels.

Conclusion

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.

Keywords

platelet physiology - cardiology - coagulation inhibitors - platelet glycoproteins

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Referenzen

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