Factor XI deficiency is associated with decreased risk for cardiovascular and venous thromboembolism events

Meir Preis, Julianna Hirsch, Antonio Kotler, Ahmad Zoabi, Nili Stein, Gad Rennert and Walid Saliba

Key points

  • Factor XI deficiency is associated with reduced risk of cardiovascular events.

  • Factor XI deficiency is associated with reduced risk of venous thromboembolism.


Factor XI deficiency is one of the rare inherited coagulation factor deficiencies. However, it incidence is high among Ashkenazi Jewish. Because factor XI displays both procoagulant and antifibrinolytic activities, it has been postulated that an underlying cardiovascular benefit may exist with factor XI deficiency. This historical cohort study was performed using the electronic database of Clalit Health Services, the largest health care provider in Israel. All adults tested for Factor XI activity between 2002 and 2014 were included in the study. Factor XI activity was classified into three categories; normal (activity >50%), mild deficiency (activity = 30-50%), and moderate-severe deficiency (activity ≤30%). The cohort was followed until December 31, 2015 for incidence of cardiovascular events (composite of myocardial infarction, stroke, and TIA) and venous thromboembolism (VTE). Of the 10,193 included patients 8,958 (88.9%) had normal factor XI activity, 690 (6.8%) had mild deficiency, and 542 (5.3%) had moderate-severe deficiency. Compared to individuals with normal activity the adjusted hazard ratio (HR) for cardiovascular events was 0.52 (95% CI, 0.31-0.87) in those with mild deficiency, and 0.57 (95% CI, 0.35-0.93) in those with moderate-severe factor XI deficiency. The incidence of VTE was lower in those with factor XI deficiency (activity <50%) compared to those with normal activity; adjusted HR = 0.26 (95% CI, 0.08-0.84). In summary, factor XI deficiency is associated with decreased incidence of cardiovascular events and VTE.

  • Submitted September 27, 2016.
  • Accepted December 20, 2016.