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CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(05): 808-817
DOI: 10.1055/s-0041-1735971
Stroke, Systemic or Venous Thromboembolism

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

Sarah Sharman Moser
1   Maccabitech, Maccabi Institute for Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel
,
Gabriel Chodick
1   Maccabitech, Maccabi Institute for Research and Innovation, Maccabi Healthcare Services, Tel Aviv, Israel
2   Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Yan G. Ni
3   Regeneron Pharmaceuticals, Inc., New York, United States
,
Dan Chalothorn
3   Regeneron Pharmaceuticals, Inc., New York, United States
,
Ming-Dauh Wang
3   Regeneron Pharmaceuticals, Inc., New York, United States
,
Alan R. Shuldiner
3   Regeneron Pharmaceuticals, Inc., New York, United States
,
Lori Morton
3   Regeneron Pharmaceuticals, Inc., New York, United States
,
Ophira Salomon
2   Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
4   Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
,
Jessica J. Jalbert
3   Regeneron Pharmaceuticals, Inc., New York, United States
› Author Affiliations Funding This work was supported by Regeneron Pharmaceuticals, Tarrytown, New York, United States. The funding source was involved in study design and in the writing of the report.
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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.

Keywords

factor XI - bleeding risk - cardiovascular events

Author Contributions

Conceptualization, methodology, or analysis: S.S.M., G.C., Y.G.N., D.C., M-.D.W., A.R.S., L.M., O.S., J.J.J.; writing—original draft preparation: S.S.M., G.C., J.J.J.; final approval: S.S.M., G.C., Y.G.N., D.C., M-.D.W., A.R.S., L.M., O.S., J.J.J.; accountability: S.S.M., G.C., Y.G.N., D.C., M-.D.W., A.R.S., L.M., O.S., J.J.J.


Supplementary Material



Publication History

Received: 30 May 2021

Accepted: 21 July 2021

Article published online:
23 September 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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