Cavallari I, Patti G. Efficacy and safety of oral anticoagulation in elderly patients with atrial fibrillation. Anatol J Cardiol. 2018;19(1):67–71. https://doi.org/10.14744/AnatolJCardiol.2017.8256.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Kapil N, Datta YH, Alakbarova N, Bershad E, Selim M, Liebeskind DS, et al. Antiplatelet and anticoagulant therapies for prevention of ischemic stroke. Clin Appl Thromb Hemost. 2017;23(4):301–18. https://doi.org/10.1177/1076029616660762.

CAS  Article  PubMed  Google Scholar 

Gurbel PA, Fox KAA, Tantry US, Ten Cate H, Weitz JI. Combination antiplatelet and oral anticoagulant therapy in patients with coronary and peripheral artery disease. Circulation. 2019;139(18):2170–85. https://doi.org/10.1161/CIRCULATIONAHA.118.033580.

CAS  Article  PubMed  Google Scholar 

Eisen A, Giugliano RP, Braunwald E. Updates on acute coronary syndrome: a review. JAMA Cardiol. 2016;1(6):718–30. https://doi.org/10.1001/jamacardio.2016.2049.

Article  PubMed  Google Scholar 

Faxon DP. Use of antiplatelet agents and anticoagulants for cardiovascular disease: current standards and best practices. Rev Cardiovasc Med. 2005;6(Suppl 4):S3-14.

PubMed  Google Scholar 

Bracey A, Shatila W, Wilson J. Bleeding in patients receiving non-vitamin K oral anticoagulants: clinical trial evidence. Ther Adv Cardiovasc Dis. 2018;12(12):361–80. https://doi.org/10.1177/1753944718801554.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Shpak M, Ramakrishnan A, Nadasdy Z, Cowperthwaite M, Fanale C. Higher incidence of ischemic stroke in patients taking novel oral anticoagulants. Stroke. 2018;49(12):2851–6. https://doi.org/10.1161/STROKEAHA.118.022636.

CAS  Article  PubMed  Google Scholar 

Naqvi IA, Kamal AK, Rehman H. Multiple versus fewer antiplatelet agents for preventing early recurrence after ischaemic stroke or transient ischaemic attack. Cochrane Database Syst Rev. 2020;(8):CD009716. https://doi.org/10.1002/14651858.CD009716.pub2

Ten Cate H, Hackeng TM, de Frutos PG. Coagulation factor and protease pathways in thrombosis and cardiovascular disease. Thromb Haemost. 2017;117(7):1265–71. https://doi.org/10.1160/TH17-02-0079.

Article  PubMed  Google Scholar 

Brass LF. Thrombin and platelet activation. Chest. 2003;124(3 Suppl):18S-25S. https://doi.org/10.1378/chest.124.3_suppl.18s.

CAS  Article  PubMed  Google Scholar 

Lowenberg EC, Meijers JC, Monia BP, Levi M. Coagulation factor XI as a novel target for antithrombotic treatment. J Thromb Haemost. 2010;8(11):2349–57. https://doi.org/10.1111/j.1538-7836.2010.04031.x.

CAS  Article  PubMed  Google Scholar 

Emsley J, McEwan PA, Gailani D. Structure and function of factor XI. Blood. 2010;115(13):2569–77. https://doi.org/10.1182/blood-2009-09-199182.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Salomon O, Steinberg DM, Koren-Morag N, Tanne D, Seligsohn U. Reduced incidence of ischemic stroke in patients with severe factor XI deficiency. Blood. 2008;111(8):4113–7. https://doi.org/10.1182/blood-2007-10-120139.

CAS  Article  PubMed  Google Scholar 

Yang DT, Flanders MM, Kim H, Rodgers GM. Elevated factor XI activity levels are associated with an increased odds ratio for cerebrovascular events. Am J Clin Pathol. 2006;126(3):411–5. https://doi.org/10.1309/QC259F09UNMKVP0R.

CAS  Article  PubMed  Google Scholar 

Gailani D, Gruber A. Factor XI as a therapeutic target. Arterioscler Thromb Vasc Biol. 2016;36(7):1316–22. https://doi.org/10.1161/ATVBAHA.116.306925.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Salomon O, Steinberg DM, Zucker M, Varon D, Zivelin A, Seligsohn U. Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis. Thromb Haemost. 2011;105(2):269–73. https://doi.org/10.1160/TH10-05-0307.

CAS  Article  PubMed  Google Scholar 

Pollack CV Jr, Kurz MA, Hayward NJ. EP-7041, a factor XIa inhibitor as a potential antithrombotic strategy in extracorporeal membrane oxygenation: a brief report. Crit Care Explor. 2020;2(9): e0196. https://doi.org/10.1097/CCE.0000000000000196.

Article  PubMed  PubMed Central  Google Scholar 

Sakimoto S, Hagio T, Yonetomi Y, Ono T, Koyama S, Hashimoto A, et al. ONO-8610539, an injectable small-molecule inhibitor of blood coagulation factor XIa, improves cerebral ischemic injuries associated with photothrombotic occlusion of rabbit middle cerebral artery. Presented at the International Stroke Conference; 21–24 February 2017; Houston, TX, USA.

Thomas D, Kanefendt FS, Schwers S, Unger S, Yassen A, Boxnick S. First evaluation of the safety, pharmacokinetics and pharmacodynamics of BAY 2433334 a small molecule targeting coagulation factor XIa in healthy young male participants. Presented at the International Society on Thrombosis and Haemostasis (ISTH) 2020 Virtual Congress; 12–14 July 2020.

Weitz JI, Bauersachs R, Becker B, Berkowitz SD, Freitas MCS, Lassen MR, et al. Effect of osocimab in preventing venous thromboembolism among patients undergoing knee arthroplasty: the FOXTROT randomized clinical trial. JAMA. 2020;323(2):130–9. https://doi.org/10.1001/jama.2019.20687.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Rosenthal RL, Dreskin OH, Rosenthal N. Plasma thromboplastin antecedent (PTA) deficiency; clinical, coagulation, therapeutic and hereditary aspects of a new hemophilia-like disease. Blood. 1955;10(2):120–31.

CAS  Article  Google Scholar 

Franchini M, Veneri D, Lippi G. Inherited factor XI deficiency: a concise review. Hematology. 2006;11(5):307–9. https://doi.org/10.1080/10245330600921964.

CAS  Article  PubMed  Google Scholar 

Lee SE, Choi YJ, Chi SI, Kim HJ, Seo KS. Factor XI deficiency and orthognathic surgery: a case report on anesthesia management. J Dent Anesth Pain Med. 2015;15(1):25–9. https://doi.org/10.17245/jdapm.2015.15.1.25.

Article  PubMed  PubMed Central  Google Scholar 

Minnema MC, Friederich PW, Levi M, von dem Borne PA, Mosnier LO, Meijers JC, et al. Enhancement of rabbit jugular vein thrombolysis by neutralization of factor XI. In vivo evidence for a role of factor XI as an anti-fibrinolytic factor. J Clin Invest. 1998;101(1):10–4. https://doi.org/10.1172/JCI781.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Wang X, Smith PL, Hsu MY, Gailani D, Schumacher WA, Ogletree ML, et al. Effects of factor XI deficiency on ferric chloride-induced vena cava thrombosis in mice. J Thromb Haemost. 2006;4(9):1982–8. https://doi.org/10.1111/j.1538-7836.2006.02093.x.

CAS  Article  PubMed  Google Scholar 

Preis M, Hirsch J, Kotler A, Zoabi A, Stein N, Rennert G, et al. Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events. Blood. 2017;129(9):1210–5. https://doi.org/10.1182/blood-2016-09-742262.

CAS  Article  PubMed  Google Scholar 

Puy C, Rigg RA, McCarty OJ. The hemostatic role of factor XI. Thromb Res. 2016;141(Suppl 2):S8–11. https://doi.org/10.1016/S0049-3848(16)30354-1.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Dilger AK, Pabbisetty KB, Corte JR, De Lucca I, Fang T, Yang W, et al. Discovery of milvexian, a high-affinity, orally bioavailable inhibitor of factor XIa in clinical studies for antithrombotic therapy. J Med Chem. 2022;65(3):1770–85. https://doi.org/10.1021/acs.jmedchem.1c00613.

CAS  Article  PubMed  Google Scholar 

Wong PC, Crain EJ, Dilger AK, Exler RR, Ewing WR, Gordon D, et al. Small-molecule factor XIa inhibitor, BMS-986177/JNJ-70033093, prevents and treats arterial thrombosis in rabbits at doses that preserve hemostasis. Poster PB0121. Presented at the International Society on Thrombosis and Haemostasis (ISTH) 2020 Virtual Congress; 12–14 July 2020.

Wang X, Qiu L, Du F, Shukla N, Nawrocki A, Chintala M. Antithrombotic effects of a novel small molecule FXIa inhibitor BMS-986177/JNJ-70033093 in a rabbit AV-shunt model of thrombosis. Poster PB0179. Presented at the International Society on Thrombosis and Haemostasis (ISTH) 2020 Virtual Congress; 12–14 July 2020.

Perera V, Wang Z, Luettgen J, Li D, DeSouza M, Cerra M, et al. First-in-human study of milvexian, an oral, direct, small molecule factor XIa inhibitor. Clin Transl Sci. 2021;15(2):330–42. https://doi.org/10.1111/cts.13148.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Perera V, Abelian G, Li D, Wang Z, Zhang L, Lubin S, et al. Single-dose pharmacokinetics of milvexian in participants with mild or moderate hepatic impairment compared with healthy participants. Clin Pharmacokinet. 2022. https://doi.org/10.1007/s40262-022-01110-9.

Article  PubMed  PubMed Central  Google Scholar 

ClinicalTrials.gov. NCT03766581. A study on BMS-986177 for the prevention of stroke in patients receiving aspirin and clopidogrel (AXIOMATIC-SSP). https://clinicaltrials.gov/ct2/show/NCT03766581 Accessed 1 Sep 2020.

Weitz JI, Strony J, Ageno W, Gailani D, Hylek EM, Lassen MR, et al. Milvexian for the prevention of venous thromboembolism. N Engl J Med. 2021;385(23):2161–72. https://doi.org/10.1056/NEJMoa2113194.

CAS  Article  PubMed  Google Scholar 

Corpataux N, Spirito A, Gragnano F, Vaisnora L, Galea R, Svab S, et al. Validation of high bleeding risk criteria and definition as proposed by the academic research consortium for high bleeding risk. Eur Heart J. 2020;41(38):3743–9. https://doi.org/10.1093/eurheartj/ehaa671.

Article  PubMed  Google Scholar 

Jackevicius CA, Lu L, Ghaznavi Z, Warner AL. Bleeding risk of direct oral anticoagulants in patients with heart failure and atrial fibrillation. Circ Cardiovasc Qual Outcomes. 2021;14(2):e007230. https://doi.org/10.1161/CIRCOUTCOMES.120.007230.

Article  PubMed  Google Scholar 

Vio R, Proietti R, Rigato M, Calo LA. Clinical evidence for the choice of the direct oral anticoagulant in patients with atrial fibrillation according to creatinine clearance. Pharmaceuticals (Basel). 2021;14(3):279. https://doi.org/10.3390/ph14030279.

CAS  Article  Google Scholar 

Alhousani M, Malik SU, Abu-Hashyeh A, Poznanski NJ, Al-Hasan S, Roth DF, et al. Using oral anticoagulants among chronic kidney disease patients to prevent recurrent venous thromboembolism: a systematic review and meta-analysis. Thromb Res. 2021;198:103–14. https://doi.org/10.1016/j.thromres.2020.11.036.

CAS  Article  PubMed  Google Scholar 

Ocak G, Rookmaaker MB, Algra A, de Borst GJ, Doevendans PA, Kappelle LJ, et al. Chronic kidney disease and bleeding risk in patients at high cardiovascular risk: a cohort study. J Thromb Haemost. 2018;16(1):65–73. https://doi.org/10.1111/jth.13904.

CAS  Article  PubMed  Google Scholar 

Lutz J, Menke J, Sollinger D, Schinzel H, Thurmel K. Haemostasis in chronic kidney disease. Nephrol Dial Transplant. 2014;29(1):29–40. https://doi.org/10.1093/ndt/gft209.

CAS  Article