Introduction:
Migraine is a debilitating
primary headache disorder with a poorly understood aetiology. An extensive body of literature supports the theory of
migraine as a systemic vascular inflammatory disorder characterised by endothelial dysfunction. It is also well-known that chronic
inflammation results in an excessive burden of oxidative stress and therefore cellular dysfunction. In this study the effects of excessive oxidative stress through the phases of female
migraine-with-aura (FMA) were evaluated by examining the health of the systems of haemostasis. Methods: Blood was obtained from 11 FMA patients at baseline and during the
headache phase of
migraine, as well as from 8 healthy age-matched female controls. Samples were analysed using thromboelastography (TEG) to evaluate viscoelastic profiles, light microscopy for erythrocyte morphology, Scanning Electron Microscopy (SEM) for erythrocyte and
fibrin clot structure, confocal microscopy for β-
amyloid detection in
fibrin clots. Results: Viscoelastic profiles from platelet poor plasma showed decreased clot reaction times in FMA at baseline (95% CI [5.56, 8.41]) vs. control (95% CI [7.22, 11.68]); as well as decreased time to maximum
thrombus generation for the same comparison (95% CI [6.78, 10.20] vs. [8.90, 12.96]). Morphological analysis of erythrocytes indicated widespread macrocytosis, poikilocytosis and eryptosis in the migraineurs. Analysis of
fibrin networks indicated that this
hypercoagulability may be a result of aberrant
fibrin polymerisation kinetics caused by the adoption of a β-
amyloid conformation of
fibrin(
ogen). Conclusion: The results reaffirm the hypercoagulable state in
migraine, and would suggest that this state is most likely a result of a systemic inflammatory state which induces oxidative damage to both erythrocytes and
fibrin(
ogen) in female episodic
migraine-with-aura. Furthermore, if the amylodogenic changes to
fibrin(
ogen) were observed in a larger cohort, this would support theories of micro-embolisation in
migraine-with-aura.