The association between thrombophilic alterations, migraine, and vascular events has been broadly investigated but not been completely clarified.
In this cross-sectional, case-control study, we included consecutive outpatients diagnosed with migraine referring to a tertiary headache center. Migraine patients were matched to headache-free control subjects. All participants were evaluated for free protein S anticoagulant, functional protein C anticoagulant, homocysteine, and antiphospholipid antibodies (aPLs). History of ischemic stroke (IS) or transient ischemic attack (TIA), coronary heart disease, and peripheral venous thrombosis was also ascertained.
We included 329 migraine patients and 329 control subjects (mean age 41 years, 77% women in both groups). Among migraine patients, 239 (72.6%) had migraine without aura and 90 (27.4%) had migraine with aura. Migraine patients had more frequently arterial hypertension, hypercholesterolemia, history of IS or TIA and, peripheral venous thrombosis compared to control subjects, whereas we found no differences in diabetes mellitus, BMI, and coronary heart disease between the two groups. At least one thrombophilic alteration was detected in 107 (32.5%) migraine patients and in 74 (22.5%) control subjects (OR = 1.66, 95% CI 1.17–2.35, p = 0.004). We identified an association of migraine with aPL positivity (OR = 2.6, 95% CI 1.5–4.7, p = 0.001) and with free protein S deficiency (OR = 4.7, 95% CI 1.6–14.0, p = 0.002), whereas we found no differences in protein C deficiency, APCR, and hyperhomocysteinemia between the two groups. Furthermore, aPL positivity and free protein S deficiency were more common in migraine patients with and without aura than in control subjects. We found that in migraine patients, aPL positivity was associated with both IS or TIA (OR = 5.6, 95% CI 1.5–20.4, p = 0.009) and with coronary heart disease (OR = 27.6, 95% CI 1.4–531.1, p = 0.028), whereas free protein S deficiency was associated with IS or TIA only (OR = 14.3, 95% CI 2.8–74.4, p = 0.002).
Our research documented a significative higher prevalence of aPL positivity and protein S deficiency in migraineurs than in controls. Data also showed an association between these alterations and some vascular thrombotic events in migraine patients. We can argue that thrombophilic disorders associated with migraine may contribute to the occurrence of vascular events.
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This study was funded by the Piedmont Region.
Conflict of interest
Dr. Cavestro, Dr. Degan, Dr. Molinari, Dr. Micca, Dr. Aloi, Dr. Mandrino, Dr. Frigeri, and Dr. Pistoia declare no conflict of interest (COI). Dr. Sacco received economic contribution from Abbott, Allergan, Eli Lilly, Novartis, TEVA.
Ethical approval and Informed consent
We obtained the approval of the Regional Health Office for targeted Research and local General Board Committee for this study (Protocol N. 474281). Informed consent was obtained from all participants.
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Cavestro, C., Degan, D., Micca, G. et al. Thrombophilic alterations, migraine, and vascular disease: results from a case-control study. Neurol Sci (2021). https://doi.org/10.1007/s10072-020-05006-z
- Hematologic diseases
- Migraine disorders
- Protein S deficiency
- Antiphospholipid antibodies