Factor XI and recurrent venous thrombosis: an observational cohort study

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 ( FXI a) reduces the risk of venous thromboembolism ( VTE ), and FXI is regarded as a potential target for anticoagulation. Patients/methods We studied the relationship between FXI a 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 FXI a. The HR s of recurrence were 0.73 (95%  CI  0.54–0.99) for patients with FXI a below the 34th percentile, and 1.05 (95%  CI  0.79–1.39) for patients with FXI a between the 34th and 67th percentiles, as compared with patients with higher FXI a. The probability of recurrence was lower among patients with FXI a below the 34th percentile than in patients with higher FXI a ( P  = 0.029). At 10 years, the probabilities of recurrence were 31%, 43% and 41% among patients with FXI a below the 34th percentile, with FXI a between the 34th and 67th percentiles, or with higher FXI a, respectively. We found a significant sex‐adjusted and age‐adjusted linear association between D‐dimer levels, measured 3 weeks after anticoagulation, and FXI a. When patients’ age and sex are taken into account, a patient with 10  IU  dL −1 lower FXI a 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 FXI a is in line with the concept that FXI is a promising target for anticoagulation.