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. 2022 May;122(5):808-817.
doi: 10.1055/s-0041-1735971. Epub 2021 Sep 23.

The Association between Factor XI Deficiency and the Risk of Bleeding, Cardiovascular, and Venous Thromboembolic Events

Sarah Sharman Moser  1 , Gabriel Chodick  1   2 , Yan G Ni  3 , Dan Chalothorn  3 , Ming-Dauh Wang  3 , Alan R Shuldiner  3 , Lori Morton  3 , Ophira Salomon  2   4 , Jessica J Jalbert  3
Affiliations

The Association between Factor XI Deficiency and the Risk of Bleeding, Cardiovascular, and Venous Thromboembolic Events

Sarah Sharman Moser et al. Thromb Haemost. 2022 May.

Abstract

The objective of this study was to assess the relationship between factor XI (FXI) deficiency and the risks of bleeding and cardiovascular (CV) events. We conducted a retrospective cohort study using data from Maccabi Healthcare Services (MHS). We identified adults with FXI deficiency (severe: <15%, partial: 15 to <50%, any deficiency: <50%) that had been tested for FXI between 2007 and 2018 and matched to patients from the general MHS population. We estimated 10-year risks of outcomes using the Kaplan-Meier approach. Using Cox proportional hazards regression, we compared outcomes among patients with versus without FXI deficiency. Less than 10% of patients tested for FXI activity had activity levels <50% (mean age: 39 years; 72.2% females). Compared with the general population, patients with any FXI deficiency were at higher risk of severe bleeding (adjusted hazard ratio [aHR]: 2.56, 95% confidence interval [CI]: 1.13-5.81; 10-year risk: 1.90%, 95% CI: 0.50-3.20% vs. 0.90%, 95% CI: 0.50-1.30%) and clinically relevant nonsevere bleeding (CRNSB) (aHR: 1.45, 95% CI: 1.08-1.97; 10-year risk: 11.60%, 95% CI: 8.30-14.80% vs. 9.20%, 95% CI: 8.00-10.40%). Severe FXI deficiency was associated with a greater risk of CRNSB. While few CV events (N = 2) and venous thromboembolisms (VTE) (N = 1) were observed in the FXI overall deficient group, there was a nonsignificant negative association between any FXI deficiency and CV events (aHR: 0.55; 95% CI: 0.13-2.36) and VTEs (aHR: 0.45; 95% CI: 0.06-3.47). Overall FXI deficiency was associated with an increased risk of severe bleeding and CRNSB. Further research is warranted to explore the lower risk of CV and VTE among patients with FXI deficiency compared with the general population.

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Conflict of interest statement

Y.G.N., D.C., M-.D.W., A.R.S., L.M., and J.J.J. are employees of Regeneron. S.S.M., G.C., O.S. have no declarations of interest.

Figures

Fig. 1
Fig. 1
Cumulative incidence of first severe bleeding and clinically relevant nonsevere bleeding among patients with factor XI deficiency (<50%) and their matched general population reference group.
Fig. 2
Fig. 2
Cumulative incidence of CV and VTE events among patients with factor XI deficiency (<50%) and their matched general population reference group. CV, cardiovascular; VTE, venous thromboembolism.
See this image and copyright information in PMC

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