Risk of Major Bleeding with Antiplatelet and/or Anticoagulation Therapy in Inherited Factor XI Deficiency: Insights from Real-World Observations

Introduction

Severe factor XI (FXI) deficiency is reported to have prevalence of 1:450 within the Ashkenazi Jewish community.[1] More modest FXI deficiency has been estimated to be more common at 1:10,000–50,000.[2]

FXI is part of the coagulation cascade and is essential in the propagation of the coagulation cascade and thrombin generation.[3] [4] There is a poor correlation between decreased FXI activity and bleeding tendency except during interventions in areas with high fibrinolytic activity.[5]

It has been postulated that an underlying cardiovascular benefit may protect the FXI-deficient subjects from developing an adverse cardiovascular event or venous thromboembolism. In the largest cohort published to date, we have demonstrated that inherited FXI deficiency confers significant cardiovascular benefit.[6]

However, some of these patients require anticoagulation or antiplatelet therapy for primary or secondary prevention of cardiovascular complications. It is unknown whether the use of these medications increases the risk for bleeding in the setting of decreased FXI levels.[7]

Authors' Contribution

V.S., N.S., W.S., and M.P. designed the study. V.S., L.D., A.W., S.P., and I.Z. collected the data. N.S., W.S., and M.P. analyzed the data. M.P. and N.S. wrote the manuscript.

Publikationsverlauf

Eingereicht: 12. Juni 2024

Angenommen: 15. Juni 2024

Accepted Manuscript online:
18. Juni 2024

Artikel online veröffentlicht:
04. Juli 2024

• References

• 1 Shpilberg O, Peretz H, Zivelin A. et al. One of the two common mutations causing factor XI deficiency in Ashkenazi Jews (type II) is also prevalent in Iraqi Jews, who represent the ancient gene pool of Jews. Blood 1995; 85 (02) 429-432
• 2 Seligsohn U. Factor XI deficiency in humans. J Thromb Haemost 2009; 7 (Suppl. 01) 84-87
• 3 Gailani D, Broze Jr GJ. Factor XI activation in a revised model of blood coagulation. Science 1991; 253 (5022): 909-912
• 4 Von dem Borne PA, Bajzar L, Meijers JC, Nesheim ME, Bouma BN. Thrombin-mediated activation of factor XI results in a thrombin-activatable fibrinolysis inhibitor-dependent inhibition of fibrinolysis. J Clin Invest 1997; 99 (10) 2323-2327
• 5 Salomon O, Steinberg DM, Seligshon U. Variable bleeding manifestations characterize different types of surgery in patients with severe factor XI deficiency enabling parsimonious use of replacement therapy. Haemophilia 2006; 12 (05) 490-493
• 6 Preis M, Hirsch J, Kotler A. et al. Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events. Blood 2017; 129 (09) 1210-1215
• 7 De Caterina R, Prisco D, Eikelboom JW. Factor XI inhibitors: cardiovascular perspectives. Eur Heart J 2023; 44 (04) 280-292
• 8 Greco A, Laudani C, Spagnolo M. et al. Pharmacology and clinical development of factor XI inhibitors. Circulation 2023; 147 (11) 897-913
• 9 Galli M, Laborante R, Ortega-Paz L. et al. Factor XI inhibitors in early clinical trials: a meta-analysis. Thromb Haemost 2023; 123 (06) 576-584