Factor XI Levels in Acute Ischemic Stroke

• To determine the relationship between elevated factors VIII, IX and XI and acute ischemic stroke as compared to other emergent events. [ Time Frame: At time of incident stroke (baseline) and at early follow-up (30-60 Days post stroke). ] [ Designated as safety issue: No ]
  

• To determine the relationship between elevated factors VIII, IX and XI and stroke subtype. [ Time Frame: 30-60 Days post stroke ] [ Designated as safety issue: No ]
  
• To determine if a relationship exists between elevated factors VIII, IX and XI and the clinical severity and stroke outcome. [ Time Frame: 30-60 Days post stroke ] [ Designated as safety issue: No ]
  
• To determine if factors VIII, IX and XI level are different in the acute phase of ischemic stroke relative to chronic phase. [ Time Frame: 30-60 Days post stroke ] [ Designated as safety issue: No ]
  
• To determine if a relationship exists between factors VIII, IX and XI levels and early stroke/TIA recurrence. [ Time Frame: 30-60 Days post stroke ] [ Designated as safety issue: No ]
  

Increased factor XI levels have been associated with venous thromboembolic disease and acute myocardial infarction. However, checking factor XI levels is not currently indicated to assess individual thromboembolic risk. Factor XI is an important protease that links the extrinsic arm of the coagulation cascade with the intrinsic arm through dual activation by both factor XII and thrombin. Since thrombin is a downstream product of factor XI, a feedback loop is created that amplifies thrombin production and ultimately results formation of a stable fibrin clot. Sufficient thrombin generation via this pathway also contributes to activation of the Thrombin-Activatable Fibrinolysis Inhibitor (TAFI). Activated TAFI downregulates fibrinolysis and has been implicated as part of the association between elevated factor XI levels and venous thromboembolic disease. One study found that functional TAFI levels of > 120% increased the risk of ischemic stroke approximately 6-fold, however, the association between Factor XI and ischemic stroke has yet to be firmly established. We recently performed a preliminary retrospective analysis of 78 patients with stroke or transient ischemic attack (TIA) and found that patients with factor XI activity levels above the 95th percentile of an age and sex matched reference population had a relative risk of 5.3 for stroke or TIA. Factor XI measurements may be able to help identify thromboembolic disease, aiding in the determination of stroke etiology.