823 MIGRAINE IN PFO PATIENTS: CHARACTERIZATION OF A PLATELET-ASSOCIATED PATHOPHYSIOLOGICAL MECHANISM BEFORE AND AFTER PFO CLOSURE: THE LEARNER STUDY

Abstract Background A strong relationship links migraine with aura (MHA) and patent foramen ovale (PFO). Increased platelet aggregation oxidative stress were documented in migraineurs. To date, no mechanisms connecting MHA to PFO have been demonstrated. Objectives perform a comprehensive analysis of activation, inflammation, status 78 aspirin-treated MHA-patients before (T0) 6-months after (T1) closure (LEARNER Study-NCT03521193-clinicaltrials.gov). The primary endpoint was regression rate relation these parameters. Methods P-selectinpos-, activated-glycoprotein IIbIIIa (aGPIIbIIIa)pos-, Tissue Factor (TF)pos-, reactive oxygen species (ROS)pos-platelets, platelet-leukocyte aggregates (PLA) microvesicles (MVs) evaluated by flow cytometry; thrombin generation (TG) Calibrated Automated Thrombogram (CAT) assay; mass spectrometry; serotonin cytokines ELISA. 12 aspirin-treated-healthy subjects (HS) enrolled for comparison. Results Migraine resolution occurred 69.7%, significant reduction 27%, while effect observed 2 patients (3.2%). Only ROSpos-platelets, TFpos-platelets -MVs significantly higher at T0, sustaining TG capacity that associated an altered blood GSSG/GSH (Oxidized/Reduced Glutathione). This phenotype reverted HS levels T1. MHA-PFO plasma, added blood, mirrored the vivo activation N-acetylcysteine blunted it. GSSG vitro reproduced condition. Aspirin had little on prothrombotic which effectively inhibited P2Y12-antagonist. Conclusion study suggests pathophysiological mechanism linking PFO, or its right-to-left shunt, MHA. show platelet-associated phenotype, sustained status. not fully controlled aspirin but P2Y12-antagonism, could play role producing prodromal symptoms migraine, it is together complete remission