Influence of Coagulation Factor VIII on Ischemic Stroke

There is considerable interest in the underlying mechanisms of cryptogenic stroke, with hypercoagulable states being widely studied. An elevated level of Factor VIII has been proposed as a potential prothrombotic marker associated with ischemic stroke. The aim of this study was to investigate the association between elevated Factor VIII levels and ischemic stroke and etiological subtype.

This retrospective observational study was conducted on subjects treated for ischemic stroke in the stroke unit of our institute between October 2018 and October 2023. Coagulative Factor VIII levels outside the acute phase (≥3 months) were measured, with elevated levels defined as >150%. Stroke etiologies (cryptogenic and non-cryptogenic: atherothrombotic, cardioembolic, lacunar, unusual, and coexistent causes), main cardiovascular risk factors, and prothrombotic biomarkers (protein C, protein S, antithrombin, anticardiolipin antibodies, anti-beta2-glycoprotein, lupus anticoagulant, and D-dimer) were recorded. Patients were categorized based on their level of coagulation Factor VIII (>150% vs. ≤150%). A comparative analysis was then conducted to assess differences associated with Factor VIII level.

A total of 68 patients were included, with a median age of 50.3 ± 12.2 years and a predominance of males (66.2%). The most frequent etiology was cryptogenic stroke (54.4%), followed by atherothrombotic (13.2%) and unusual causes (11.8%). Elevated Factor VIII levels were observed in 41.2% of patients. No significant associations were found between elevated Factor VIII and cryptogenic stroke (p = 0.27), stroke subtype (p = 0.38), comorbidities, or other thrombophilia biomarkers. However, a weak correlation was observed between elevated Factor VIII and antithrombin levels outside the normal range (p = 0.039), and a significant association was found between Factor VIII levels and prior atrial fibrillation (AF, p = 0.04).

Although a high coagulation Factor VIII level was frequently observed in patients with ischemic stroke, this was not associated with cryptogenic stroke in the present cohort. Further studies with a larger sample size are warranted to clarify whether elevated Factor VIII is independently associated with ischemic stroke subtype, and whether elevated levels are a secondary finding related to inflammatory or systemic factors.