Factor XI Levels in Acute Ischemic Stroke

Overview

The purpose of this study is to evaluate the utility of measuring coagulation factor activities in the setting of acute ischemic stroke, as potential markers of inherited thrombotic risk. The investigators will determine if relationships exist between coagulation factors, including factor VIII, factor IX, and factor XI and clinical diagnosis, classification, and outcome. The investigators will determine if any significant elevations of these factor activities are independent thrombotic risk factors. Null Hypothesis: There is no statistical difference between coagulation factors, including factors VIII, IX, or XI activity levels in patients having acute ischemic stroke as compared to acute stroke mimics.

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.

Conditions