A growing body of literature suggests that migraineurs, particularly those with aura, have an increased risk for ischemic stroke, but not via enhanced atherosclerosis. The theory that micro-emboli induced ischemia provokes cortical spreading depression (ie, symptomatic aura) in migraineurs but transient ischemic attacks in others highlights a potential role for hypercoagulability as a link between migraine (with aura) and stroke.
Our objective is to summarize the literature evaluating the association of migraine with various acquired or inheritable thrombophilic states, including those related to elevated estrogen levels, endothelial activation and dysfunction, antiphospholipid antibodies (aPL), deficiency of coagulation inhibitors, and presence of certain genetic polymorphisms.
Although definitive studies are lacking, a preponderance of available evidence links migraine, and especially aura, to increased levels of estradiol (eg, oral contraceptive pill [OCP] use, pregnancy), thrombo- and erythrocytosis, von Willebrand factor (vWF) antigen, fibrinogen, tissue plasminogen activator (tPA) antigen, and endothelial microparticles. Studies of a link to migraine are conflicting for aPL, homocysteine, Protein S, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. No association with migraine was found in meta-analyses of Factor V Leiden, and of prothrombin gene mutation. Within a large, young ischemic stroke sample, migraine with aura was associated with a thrombophilic state and with patent foramen ovale (PFO). In the non-stroke population, meta-analyses show an association of PFO and migraine with aura (MA), but two population-based studies do not support the link.
For persons with MA and (1) a personal history or family history of thrombosis, or (2) MRI evidence of micro-vascular ischemia or of stroke, an evaluation for hypercoagulability is warranted. In cases of MA alone, consider screening for markers of endothelial activation (eg, vWF, high sensitivity c-reactive protein [hs CRP], and fibrinogen). Rigorous management of other stroke risk factors is paramount, but efficacy of anti-thrombotic agents in the treatment of migraine is unproven. Closure of PFO is not routinely recommended based on negative randomized trials.