Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis

Abstract

Factor XI (FXI) plays a dual role in haemostasis and thrombosis. It contributes to thrombin generation and promotes inhibition of fibrinolysis. Severe FXI deficiency was shown to confer protection against arterial and venous thrombosis in animal models without compromising haemostasis. We have previously shown that patients with severe FXI deficiency have a low incidence of ischaemic stroke, but display the usual incidence of myocardial infarction. In the present study, we compared the incidence of deep-vein thrombosis (DVT) in 219 unrelated patients with severe FXI deficiency aged 20-94 to the incidence in a large population-based study. No cases of DVT were observed in the FXI-deficient cohort, a result that is significantly lower than the expected number (4.68) computed from the population-based study. The low incidence remains statistically significant when compared to three other population-based studies. These data suggest that severe FXI deficiency provides protection against DVT.

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

“…22 The reduced risk of VTE associated with factor XI deficiency is in line with a previous study that observed not 1 case of DVT among 219 adults with severe factor XI deficiency, a finding that was significantly different from the expected number of DVTs from a population-based cohort. 12 In our study, however, the observation that no patient with moderate to severe factor XI deficiency had a VTE event and the observed reduced risk of VTE with mild factor XI deficiency suggest a dose-response relationship between factor XI deficiency and VTE. These findings are supported by the results of a randomized controlled trial that compared enoxaparin with 2 different dosages of factor XI antisense oligonucleotide that specifically reduced factor XI levels, in patients undergoing elective unilateral total knee arthroplasty.…”

“…11 Because factor XI displays both procoagulant and antifibrinolytic activities, it has been postulated that an underlying cardiovascular benefit may protect factor XI-deficient subjects. Small studies showed that severe factor XI deficiency is associated with reduced incidences of deep vein thrombosis 12 and ischemic stroke, 13 but not with myocardial infarction (MI).…”

“…Whereas previous studies included a small number of patients, ranging from 96 to 219 patients, who came from the same referral center for thrombosis and hemostasis disorders, they are raising concern about highly selective patients as a result of referral bias. [12][13][14] The majority (77.7%) of the patients included in our study were young women in their childbearing age (median age 33.5 years; IQR, 27.8-42.7). At this age group, women are prone to bleeding episodes because of, for example, heavy menstrual bleeding and intrapartum hemorrhage, which could have led to excessive testing for factor XI activity.…”

Epidemiologic and clinical data linking factors XI and XII to thrombosis

“…22 In a study of adult fXI-deficient patients in Israel, the rate of DVT (0/219) was statistically lower than the expected rate in the matched general population. Conversely, elevated fXI antigen levels were found to be a risk factor for VTE in the LITE study, with an odds ratio (OR) for VTE with fXI levels in the top quintile of 1.8 [95% confidence interval (CI), 1.3-2.7].…”

Coagulation and the Vessel Wall in Pulmonary Embolism

“…28,29 Patients with severe deficiency of factor XI, the substrate for activated FXII, have a reduced incidence of DVT. 30 Naturally occurring polyphosphates such as extracellular DNA, RNA, and inorganic polyphosphate are potent activators of the coagulation cascade ( Fig. 1) and represent a potential therapeutic target for novel anticoagulation strategies.…”