Factor XI Inhibition for the Prevention of Venous Thromboembolism: An Update on Current Evidence and Future perspectives

Geraldine Poenou,1 Teona Dimitru Dimitru,1– 3 Ludovic Lafaie,4,5 Valentine Mismetti,5,6 Marco Heestermans,5,7 Laurent Bertoletti1,5,8 1Therapeutic and Vascular Medicine Department, University Hospital of Saint Etienne, Saint Etienne, France; 2Internal Medicine Department, University Hospital Santa Lucía, Cartagena, Murcia, Spain; 3Catholic University San Antonio, Murcia, Spain; 4Geriatric Department, University Hospital of Saint Etienne, Saint Etienne, France; 5INSERM, UMR1059, Haemostasis and Vascular Dysfunction Team, Jean Monnet University, Saint-Etienne, F-42055, France; 6Pneumology Department, University Hospital of Saint Etienne, Saint Etienne, France; 7Auvergne-Rhône-Alpes French Blood Donation Agency, Saint-Etienne, F-42100, France; 8INSERM, CIC-1408, University Hospital of Saint Etienne, Saint Etienne, FranceCorrespondence: Laurent Bertoletti, Therapeutic and Vascular Medicine Department, University Hospital of Saint Etienne, Saint Etienne, France, Tel +33477827771, Fax +33477820482, Email Laurent.bertoletti@gmail.comAbstract: During the past decade, emergence of direct oral anticoagulants (DOACs) has drastically improved the prevention of thrombosis. However, several unmet needs prevail in the field of thrombosis prevention, even in the DOACs’ era. The use of DOACs is still constrained and the drugs cannot be administered in every clinical scenario, such as an increased anticoagulant-associated bleeding risk, particularly in some specific populations (cancer – notably those with gastrointestinal or genitourinary cancer – and frail patients), the impossibility to be used in certain patients (eg, end-stage kidney failure during hemodialysis, pregnancy and breastfeeding), and their lack of efficacy in certain clinical scenarios (eg, mechanical heart valves, triple-positive antiphospholipid syndrome). Efforts to find a factor that upon antagonization prevents thrombosis but spares haemostasis have resulted in the identification of coagulation factor XI (FXI) as a therapeutic target. After briefly recapitulating the role of factor XI in the balance of haemostasis, we propose a narrative review of the key data published to date with compounds targeting factor XI to prevent thrombosis as well as the main ongoing clinical studies, opening up prospects for improving the care of patients requiring thrombosis prevention.Keywords: FXI inhibitor, venous thromboembolic events, thromboprophylaxis, anticoagulant, clinical trials