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. 2025 Mar;32(3):e70063.
doi: 10.1111/ene.70063.

Coagulation Factors and White Matter Hyperintensities in Middle-Aged Women With and Without Migraine and Ischemic Stroke

Mariam Ali  1 , Nelleke van der Weerd  1   2 , Hendrikus J A van Os  1   3 , Annelise E Wilms  1 , Ghislaine Holswilder  4 , Katie M Linstra  1 , Thijs W van Harten  4   5 , Suzanne C Cannegieter  6 , Bob Siegerink  6 , Bart J M van Vlijmen  7 , L Renee Ruhaak  8 , Nyika D Kruyt  1 , Mark C Kruit  4 , Antoinette Maassen Van Den Brink  9 , Gisela M Terwindt  1 , Marieke J H Wermer  1   10 ; CREW Consortium
Affiliations

Coagulation Factors and White Matter Hyperintensities in Middle-Aged Women With and Without Migraine and Ischemic Stroke

Mariam Ali et al. Eur J Neurol. 2025 Mar.

Abstract

Background: Migraine increases the risk of ischemic stroke and white matter hyperintensities (WMH), especially in women. Underlying shared mechanisms may include endothelial activation and hypercoagulability. We assessed these markers in middle-aged women with and without migraine and ischemic stroke to explore their role in WMH development.

Methods: We cross-sectionally measured fibrinogen and von Willebrand factor antigen (VWF:Ag) levels as markers of endothelial activation, and factor (F)IX and FXI activity (FXI:C) as markers of hypercoagulability in four groups of women aged 40-60 years with (1)ischemic stroke, (2)migraine, (3)both ischemic stroke and migraine, and (4)no stroke or migraine. Multivariable linear regression estimated mean differences in coagulation factor levels between groups 1 and 3, with group 4 as the reference.

Results: Among 166 women (mean age:51 years), (1) 45 had ischemic stroke, (2) 38 had migraine, (3) 48 had both, and (4) 35 had no stroke or migraine. Mean fibrinogen, FIX, and FXI:C levels were similar in all groups compared with group 4. VWF:Ag levels were higher in the ischemic stroke with migraine group (170 [57]%; adjusted β = 31%; 95% CI = 6%-56%) compared with group 4, but not in the other groups. There was no association between coagulation factors and WMH volume in any group.

Conclusions: In women with both stroke and migraine, VWF:Ag levels were increased, while fibrinogen, FIX, and FXI:C were not. This suggests that endothelial activation might be more relevant than a procoagulant state alone in the pathophysiology of ischemic stroke in women with migraine. Coagulation factors did not seem to be related to WMH volume, suggesting other mechanisms may be involved in their development.

Keywords: coagulation factors; ischemic stroke; migraine; white matter hyperintensities; women.

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Conflict of interest statement

G.M.T. reports independent support from the Dutch Research Council, DHF, Dutch Brain Foundation, Dioraphte, Clayco Foundation and consultancy for Novartis, Lilly, Teva, Abbvie, Organon, Pfizer, and Lundbeck. A.E.W. and G.M.T. report grant support from the European Community (101070917), Stichting Dioraphte (20010407), and Clayco Foundation. A.M.V.D.B. received honoraria and research/travel grants from Allergan/AbbVie, Amgen/Novartis, Eli Lilly, Manistee, Pfizer, Satsuma, Teva, and Tonix as well as independent support from the Dutch Research Council and ZonMw. T.W.H. received support from DHF and NWO under the joint strategic research program, “Earlier recognition of cardiovascular diseases.”

Figures

FIGURE 1
FIGURE 1
Assocation between coagulation factor levels and total WMH volume. VWF, von Willebrand factor; WMH, white matter hyperintensities.
See this image and copyright information in PMC

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