Sex Differences in Hemostatic Factors in Patients With Ischemic Stroke and the Relation With Migraine-A Systematic Review.

Jan W. Schoones,Nyika D. Kruyt,Marieke J. H. Wermer,Bob Siegerink,Nelleke van der Weerd,Arn M. J. M. van den Maagdenberg,Mariam Ali,Hine J. A. van Os

doi:10.3389/fncel.2021.711604

Abstract

Background: Women are more affected by stroke than men. This might, in part, be explained by sex differences in stroke pathophysiology. The hemostasis system is influenced by sex hormones and associated with female risk factors for stroke, such as migraine.Aim: To systematically review possible sex differences in hemostatic related factors in patients with ischemic stroke in general, and the influence of migraine on these factors in women with ischemic stroke.Results: We included 24 studies with data on sex differences of hemostatic factors in 7247 patients with ischemic stroke (mean age 57–72 years, 27–57% women) and 25 hemostatic related factors. Levels of several factors were higher in women compared with men; FVII:C (116% ± 30% vs. 104% ± 30%), FXI (0.14 UI/mL higher in women), PAI-1 (125.35 ± 49.37 vs. 96.67 ± 38.90 ng/mL), D-dimer (1.25 ± 0.31 vs. 0.95 ± 0.24 μg/mL), and aPS (18.7% vs. 12.0% positive). In contrast, protein-S (86.2% ± 23.0% vs. 104.7% ± 19.8% antigen) and P-selectin (48.9 ± 14.4 vs. 79.1 ± 66.7 pg/mL) were higher in men. Most factors were investigated in single studies, at different time points after stroke, and in different stroke subtypes. Only one small study reported data on migraine and hemostatic factors in women with ischemic stroke. No differences in fibrinogen, D-dimer, t-PA, and PAI-1 levels were found between women with and without migraine.Conclusion: Our systematic review suggests that sex differences exist in the activation of the hemostatic system in ischemic stroke. Women seem to lean more toward increased levels of procoagulant factors whereas men exhibit increased levels of coagulation inhibitors. To obtain better insight in sex-related differences in hemostatic factors, additional studies are needed to confirm these findings with special attention for different stroke phases, stroke subtypes, and not in the least women specific risk factors, such as migraine.

Highlights

Stroke is the third most disabling disease worldwide
D-dimer, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1) levels were found between women with and without migraine
Our systematic review suggests that sex differences exist in the activation of the hemostatic system in ischemic stroke

Summary

Introduction

Women are affected because of a higher stroke incidence and a worse outcome compared with men (Girijala et al, 2017) Evidence accumulates that these differences might, in part, be explained by sex-specific pathophysiological mechanisms underlying stroke (Demel et al, 2018). The comorbidity between ischemic stroke and cardiovascular disease with migraine is recognized already for decades (Kurth et al, 2012; Sacco et al, 2017; Adelborg et al, 2018; Demel et al, 2018) Both men and women with migraine with aura have an approximately twofold increased risk of ischemic stroke (Adelborg et al, 2018). The hemostasis system is influenced by sex hormones and associated with female risk factors for stroke, such as migraine

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