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Factor XI Level Associated with Stroke

Factor XI is a component of the intrinsic pathway of coagulation. It plays two roles in promoting hemostasis - a procoagulant action by increasing formation of fibrin, and an antifibrinolytic action by promoting the activity of a fibrinolytic inhibitor. Factor XI deficiency results in a mild to moderate bleeding disorder. A recent study indicated that high levels of factor XI are associated with venous thrombosis (N Engl J Med 2000;342:696-701). The authors reported a two-fold increased risk of venous thrombosis in subjects whose factor XI was above the 90th percentile for the population (factor XI level greater than 120%).

The association of factor XI levels with arterial thrombosis has not been established. Two studies suggested an association between elevated factor XI levels and coronary artery disease. A recent retrospective study investigated a possible relationship between factor XI levels and stroke (Am J Clin Pathol 2006;126:411-415). The subjects, all younger than 55 years, included 65 patients with stroke, 13 with TIA, and 17 with venous thrombosis. Forty healthy control subjects were age and sex-matched to the patient population. Factor XI activity and C-reactive protein (CRP) levels were assayed. Factor XI activity in the reference group ranged from 57%-155%, with a 95th percentile value of 141%. In the 78 patients with stroke or TIA, factor XI ranged from 55%-675%, and 22% of the patients had values higher than the 95th percentile of the reference population. The 17 patients with venous thrombosis had factor XI levels ranging from 71% to 196%, and 18% of these patients had values higher than the reference population 95th percentile. From this data, the odds ratio for stroke or TIA in patients with factor XI activity higher than the 95th percentile of the reference population is 5.3; for venous thrombosis this odds ratio is 4.1. There was no correlation between factor XI and CRP values, indicating that factor XI is not an acute phase reactant.

In summary, there is evidence that elevated factor XI activity is associated with both venous thrombosis and cerebrovascular disease. Further studies are warranted to determine whether this finding may be utilized to identify at-risk populations.

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