Hamostaseologie 2023; 43(01): 028-036
DOI: 10.1055/a-1984-7021
Review Article

A Review of FXIa Inhibition as a Novel Target for Anticoagulation

Ioannis Koulas
1   The Institute of Health Systems Science at the Feinstein Institutes for Medical Research, Manhasset, New York, United States
Alex C. Spyropoulos
1   The Institute of Health Systems Science at the Feinstein Institutes for Medical Research, Manhasset, New York, United States
2   Northwell Health at Lenox Hill Hospital, New York, New York, United States
3   The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, United States
› Author Affiliations
Funding/Acknowledgment This work was made possible in part by funding from the Broxmeyer Fellowship in Clinical Thrombosis.


Limitations of vitamin K antagonists as chronic oral anticoagulant therapy have largely been supplanted by direct factor IIa and factor Xa inhibitor oral anticoagulants with similar efficacy but an overall better safety profile, lack of routine monitoring, and very limited drug–drug interactions compared with agents such as warfarin. However, an increased risk of bleeding remains even with these new-generation oral anticoagulants in fragile patient populations, in patients requiring dual or triple antithrombotic therapy, or high bleed risk surgeries. Epidemiologic data in patients with hereditary factor XI deficiency and preclinical studies support the notion that factor XIa inhibitors have the ability to be an effective but potentially safer alternative to existing anticoagulants, based on their ability to prevent thrombosis directly within the intrinsic pathway without affecting hemostatic mechanisms. As such, various types of factor XIa inhibitors have been studied in early phase clinical studies, including inhibitors of the biosynthesis of factor XIa with antisense oligonucleotides or direct inhibitors of factor XIa using small peptidomimetic molecules, monoclonal antibodies, aptamers, or natural inhibitors. In this review, we discuss how different types of factor XIa inhibitors work and present findings from recently published Phase II clinical trials across multiple indications, including stroke prevention in atrial fibrillation, dual pathway inhibition with concurrent antiplatelets post–myocardial infarction, and thromboprophylaxis of orthopaedic surgery patients. Finally, we refer to ongoing Phase III clinical trials of factor XIa inhibitors and their potential to provide definitive answers regarding their safety and efficacy in preventing thromboembolic events in specific patient groups.

Publication History

Received: 10 October 2022

Accepted: 19 November 2022

Article published online:
20 February 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany