Hemostatic Profile Associated with Migraine with Aura

Nearly 15% of the population in the USA experiences migraine. One subtype of migraine that is not well understood is migraine with aura (MA). Individuals who experience MA often see flashing lights, blind spots, or jagged lines in their visual field prior to onset of their migraine headaches.

Individuals who experience MA also face a heightened risk of stroke and cardiovascular disease, although scientists continue to explore why this correlation exists. Based on prior studies, it is controversial whether enhanced atherosclerosis among individuals with MA is likely to explain the migraine association with stroke, suggesting the existence of alternative mechanisms including endothelial activation or a potential role of hypercoagulability and microemboli.

An international team of Medical Scientists led by Brigham and Women's Hospital (Boston, MA, USA) investigated potential causal relationships between hemostatic profiles and migraine by leveraging largescale genome-wide association study (GWAS) summary statistics for migraine and migraine subtypes (MA and migraine without aura [MO]), and for eight hemostatic factors (including plasma levels or activities of fibrinogen, D-dimer, coagulation factor VII [FVII], coagulation factor VIII [FVIII], coagulation factor XI [FXI], von Willebrand factor [vWF], tissue plasminogen activator [tPA], and plasminogen activator inhibitor-1 [PAI-1] among up to 120,246 individuals), two hemostasis clinical tests (activated partial thromboplastin time [aPTT] and prothrombin time/international normalized ratio [PT/INR], which are commonly used to screen for coagulation-factor deficiencies), as well as serum concentrations of two forms of fibrinopeptide A (fibrinopeptide A [ADSGEGDFXAEGGGVR*] and phosphorylated fibrinopeptide A [ADpSGEGDFXAEGGGVR*]).

The investigators found a strong association between four coagulation factors and migraine susceptibility. They observed that genetically increased levels of three blood clotting factors: coagulation factor VIII, von Willebrand factor, and phosphorylated fibrinopeptide A, and genetically decreased levels of fibrinogen (a protein important in the late stages of the blood clotting process) were all associated, in part, with migraine susceptibility. Interestingly, scientists did not find this association among individuals who experience migraine without aura (MO), indicating a specific relationship between these hemostatic factors and MA.

Yanjun Guo, MD, PhD, of the Division of Preventative Medicine at the Brigham and the first author of the study, said, “It is very exciting that by using Mendelian randomization we were able to show that hemostatic factors are associated with MA. And because in the observational studies we saw that MA patients have a higher risk of stroke, these findings may reveal a potential connection between MA and stroke.”

The authors concluded that their findings suggest potential causal roles of genetically determined elevated FVIII, vWF, phosphorylated fibrinopeptide A, and decreased fibrinogen in migraine susceptibility, especially for MA, but the effects of FVIII and vWF on migraine are not independent from each other. The study was originally published online on April 1, 2021 in the journal Neurology.

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