Increased Risk of Cerebrovascular Events Is Associated with Elevated Factor XI Activity.

High levels of factor XI as measured by antigenic methods have been implicated as a risk factor for deep venous thrombosis, and there is limited evidence that increased factor XI activity as measured by a functional assay is associated with cardiovascular disease. In the current study, we evaluated factor XI antigen, factor XI functional activity and high-sensitivity C-reactive protein (hs-CRP) from 123 patients under the age of 55 with normal prothrombin and partial thromboplastin times undergoing evaluation for a hypercoagulable state. Of the 123 patients, 80 had a history suggestive of arterial thrombosis (65 with stroke symptoms, 13 with transient ischemic attack symptoms, and 2 with other arterial thrombi), 17 had a history of venous thrombosis, and 26 had indeterminate histories for arterial or venous thrombosis. 40 age- matched healthy subjects were used to determine the upper limit of normal for factor XI activity as defined by the 95^th percentile value (141%). 17/80 (21%) of patients with arterial thrombosis and 3/17 (18%) of the patients with venous thrombosis had above normal factor XI activity levels. Based on this, those with elevated factor XI activity have a relative risk of 5.3 for a cerebrovascular event. Regression analysis demonstrates that factor XI activity appears to correlate with factor XI antigen level (slope=0.79 and R=0.67), but there is no correlation between factor XI activity or factor XI antigen levels and hs-CRP (R= −.003 and R=.096 respectively). Our findings suggest that elevated factor XI activity is associated with an increased risk for cerebrovascular events and confirms that elevated factor XI levels are also associated with increased risk for venous thrombosis. In addition, assessment of factor XI levels by two methods, both functional activity and antigenic level, appear to correlate with one another to a fair degree suggesting that increased activity is likely related to increased levels of the protein itself. Lastly, lack of correlation with hs-CRP suggests that factor XI is not an acute-phase reactant.