Factor XI and recurrent venous thrombosis: an observational cohort study

Abstract

Essentials Factor XI is a potential target for anticoagulation. The association between factor XI and venous thrombosis recurrence was tested in a cohort study. Low factor XI was associated with reduced risk of recurrent venous thrombosis. A sex-and age-adjusted linear association between D-Dimer and factor XI was found. Summary: Background and objectives Low factor XI activity (FXIa) reduces the risk of venous thromboembolism (VTE), and FXI is regarded as a potential target for anticoagulation. Patients/methods We studied the relationship between FXIa and VTE in 851 patients with unprovoked VTE in whom anticoagulation had been stopped. Results Recurrent VTE was recorded in 265 patients. The sex-adjusted and age-adjusted hazard ratio (HR) of recurrence was 0.94 (95% confidence interval [CI] 0.89–0.99) for each decrease of 10 IU dL−1 in FXIa. The HRs of recurrence were 0.73 (95% CI 0.54–0.99) for patients with FXIa below the 34th percentile, and 1.05 (95% CI 0.79–1.39) for patients with FXIa between the 34th and 67th percentiles, as compared with patients with higher FXIa. The probability of recurrence was lower among patients with FXIa below the 34th percentile than in patients with higher FXIa (P = 0.029). At 10 years, the probabilities of recurrence were 31%, 43% and 41% among patients with FXIa below the 34th percentile, with FXIa between the 34th and 67th percentiles, or with higher FXIa, respectively. We found a significant sex-adjusted and age-adjusted linear association between D-dimer levels, measured 3 weeks after anticoagulation, and FXIa. When patients’ age and sex are taken into account, a patient with 10 IU dL−1 lower FXIa is expected to have a 2.79% (95% CI 0.95–4.59%) lower D-dimer value (P = 0.003). Conclusions Our findings of a lower thrombosis risk and less pronounced hemostatic system activation among patients with low FXIa is in line with the concept that FXI is a promising target for anticoagulation.