Activated factor IX, factor XI and tissue factor identify patients with permanent atrial fibrillation treated with warfarin who are at risk of ischemic stroke

INTRODUCTION: Previously, we have demonstrated that significant proportions of patients with various cardiovascular diseases have active tissue factor and active factor XIa in their plasma. In the current study, we evaluated active tissue factor and active factors (F)XI and FIX in plasma from patients with atrial fibrillation. MATERIAL AND METHODS: In 110 consecutive patients with permanent atrial fibrillation receiving warfarin, we determined active tissue factor, together with plasma FIXa and FXIa, using clotting assays by measuring the response to inhibitory monoclonal antibodies. RESULTS: Sixteen (14.5%) patients had detectable active tissue factor and active FXIa, including 11 subjects with both factors, while FIXa was observed in 28 (25.7%) patients. The three positive groups did not differ from the patients without these factors with regard to demographic and clinical characteristics. Von Willebrand factor was higher in the active tissue factor-positive group (p < 0.0001) and FXIa-positive group (p = 0.0037). Individuals positive for active tissue factor and FXIa had higher plasma interleukin-6 levels (p = 0.0014 and 0.0322, respectively). The presence of active tissue factor, FXIa and FIXa in anticoagulated patients with permanent atrial fibrillation correlated with elevated von Willebrand factor and interleukin-6. During a 3-year follow-up, ischemic stroke (n = 12, 10.9%) occurred more commonly among atrial fibrillation patients who had circulating TF (p = 0.002) or FXIa (p = 0.013). CONCLUSIONS: These data suggest that circulating active coagulation factors, in particular TF and FXIa, can be detected despite oral anticoagulation in a significant proportion of patients with atrial fibrillation, and could represent novel markers of persistent prothrombotic alterations predisposing to ischemic stroke.