Shunt-related platelet activation in patients with patent foramen ovale

Background Patent foramen ovale (PFO) is present in about one-third of the population, and percutaneous PFO closure is recommended for the secondary prevention of cryptogenic stroke. Evidence suggests that patients with PFOs exhibit a prothrombotic phenotype, which is thought to be associated with an increased incidence of migraines and early-onset dementia. Percutaneous PFO closure has indeed been associated with improvements in migraine symptoms. However, the underlying mechanism remains unclear. Aim The study aimed to investigate whether platelets are activated at the site of PFO due to a left-to-right shunt, and if so, whether this activation ceases after PFO closure. Methods This prospective, single-centre, observational study included patients undergoing percutaneous PFO closure between February 2024 and January 2026. Blood samples were collected from the right atrium before and immediately after closure. We assessed platelet activation by quantifying adenosine diphosphate (ADP)-stimulated CD62P (P-selectin) expression using flow cytometry. Migraine was classified according to the International Classification of Diseases (ICD) criteria, and severity was assessed using the Migraine Disability Assessment (MIDAS) questionnaire and the Headache Impact Test (HIT-6). Results A total of 125 patients were included in the study. Mean age was 51.2 years (± SD 11.9) and 76 patients (60.8%) were male. Of those, 21 patients had migraines (16.8%), 15 (71.4%) of whom were female and six (28.6%) of whom were male. ADP stimulation revealed significantly higher CD62P+ count in samples from the right atrium before device closure, compared to samples collected immediately after closure (p<0.001), with a mean reduction of 6.2% (± SD 5.9; Figure 1). Further, multivariable linear regression analysis revealed a significant interaction between sex and migraine, indicating that female patients with migraines experienced a greater reduction in platelet activation following PFO closure (estimated effect size β=7.54, 95% CI 1.58–13.49, p = 0.014). Conclusion Left-to-right shunt, as occurs in PFO, leads to measurable changes in platelet activation that decrease significantly immediately after PFO closure. These findings are particularly relevant for female patients with migraines, because our data support a sex-specific mechanism in which women with migraines appear to have a greater biological benefit from PFO closure.