Migraine in Patients Undergoing PFO Closure: Characterization of a Platelet-Associated Pathophysiological Mechanism: The LEARNER Study

•Patients experiencing MHA-PFO on aspirin are characterized by a marked thrombin generation capacity sustained by an elevated number of platelets and MVs expressing a functionally active tissue factor.•MHA-PFO patients are also characterized by an altered oxidative stress status, ie, increased platelet ROS production and blood GSSG/GSH ratio.•This prothrombotic condition fully reverts upon PFO closure and is associated with 100% migraine remission.•MHA-PFO plasma and GSSG, added to blood of healthy subjects, mirrored the in vivo platelet activation and this effect is blunted by N-acetylcysteine, thus supporting the etiopathogenetic role of oxidative stress in this clinical setting.•Aspirin had little effect on the platelet prothrombotic phenotype that was better controlled by P2Y12 antagonist.