{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:02:55Z","timestamp":1791198175849,"version":"4.1.0"},"reference-count":171,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Thromboembolic diseases impose a significant burden on global health. However, the currently approved anticoagulant drugs, including heparin, vitamin K antagonists, and direct oral anticoagulants (DOACs), all carry certain bleeding risks. The proteases inhibited by these drugs play crucial roles in both pathological thrombosis formation and normal hemostasis. Therefore, how to effectively anticoagulate without increasing bleeding has become the core direction of clinical research. Factor XI (FXI) and activated factor XI (FXIa) are increasingly recognized as regulators at the interface between coagulation and immunothrombosis. Experimental studies suggest that FXI\/FXIa may interact with neutrophil extracellular trap formation (NETosis), complement activation, and inflammatory signaling pathways, raising the possibility that FXI\/FXIa inhibition could have broader effects beyond anticoagulation. However, the clinical relevance of these immunomodulatory functions remains to be established. Genetic evidence also supports this characteristic: FXI deficiency can reduce the risk of venous thromboembolism (VTE) and does not lead to spontaneous bleeding, whereas elevated FXI levels increase thrombotic events. Thus, FXI\/FXIa have become promising targets due to their unique biological properties. Currently, FXI inhibitors have been developed in various formulations, including antisense oligonucleotides, monoclonal antibodies, and small - molecule synthetic drugs. The phase II clinical trials of FXI inhibitors have achieved positive results in the treatment of knee joint replacement surgery, end - stage renal disease, atrial fibrillation (AF), acute non - cardiogenic thromboembolic ischemic stroke, and high - risk transient ischemic attack (TIA). Phase III clinical trials of certain FXI inhibitors are also being actively conducted. The review focuses on the spatial structure of FXI, its role in the coagulation pathway and pathological thrombosis formation, immunothrombosis and gene polymorphisms. It introduces the current cutting - edge drugs in development, summarizes the results of completed clinical trials, and discusses the current research progress.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1925585","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:39:39Z","timestamp":1791196779000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond traditional anticoagulants: exploring the future of thromboembolism treatment with FXI inhibitors"],"prefix":"10.3389","volume":"17","author":[{"given":"Hui","family":"Yuan","sequence":"first","affiliation":[{"name":"School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Personalized Drug Research and Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinan","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Personalized Drug Research and Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People\u2019s Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.115.306841","article-title":"Global burden of thrombosis","volume":"118","author":"Wendelboe","year":"2016","journal-title":"Circ Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00757-8","article-title":"Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990\u20132021: a systematic analysis for the Global Burden of Disease Study 2021","volume":"403","year":"2024","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(16)30514-1","article-title":"Deep vein thrombosis and pulmonary embolism","volume":"388","author":"Di Nisio","year":"2016","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5273(88)90291-4","article-title":"The prevalence and pattern of pulmonary thromboembolism in the Chinese in Kong Kong","volume":"20","author":"Woo","year":"1988","journal-title":"Int J Cardiol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.109.921460","article-title":"Risk factors for venous thromboembolism","volume":"121","author":"Holst","year":"2010","journal-title":"Circulation"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2023.283682","article-title":"Novel horizons in anticoagulation: the emerging role of factor XI inhibitors across different settings","volume":"109","author":"Cohen","year":"2024","journal-title":"Haematologica"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13148","article-title":"First\u2010in\u2010human study of milvexian, an oral, direct, small molecule factor XIa inhibitor","volume":"15","author":"Perera","year":"2021","journal-title":"Clin Transl Sci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"5165","DOI":"10.1038\/s41598-022-08768-y","article-title":"Safety, pharmacokinetics, and pharmacodynamics of milvexian in healthy Japanese participants","volume":"12","author":"Perera","year":"2022","journal-title":"Sci Rep"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1160\/th10-05-0307","article-title":"Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis","volume":"105","author":"Zivelin","year":"2011","journal-title":"Thromb Haemostasis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v124.21.lba-1.lba-1","article-title":"Factor XI antisense oligonucleotide for prevention of venous thrombosis","volume":"372","author":"B\u00fcller","year":"2015","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.04031.x","article-title":"Coagulation factor XI as a novel target for antithrombotic treatment","volume":"8","author":"L\u00f6wenberg","year":"2010","journal-title":"J Thromb Haemostasis"},{"key":"B12","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1161\/circulationaha.122.062353","article-title":"Pharmacology and clinical development of factor XI inhibitors","volume":"147","author":"Greco","year":"2023","journal-title":"Circulation"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1021\/bi00357a018","article-title":"Amino acid sequence of human factor XI, a blood coagulation factor with four tandem repeats that are highly homologous with plasma prekallikrein","volume":"25","author":"Fujikawa","year":"2002","journal-title":"Biochemistry"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023020719","article-title":"Biology of factor XI","volume":"143","author":"Moellmer","year":"2024","journal-title":"Blood"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1095","article-title":"Crystal structure of the factor XI zymogen reveals a pathway for transactivation","volume":"13","author":"Papagrigoriou","year":"2006","journal-title":"Nat Struct Mol Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.7.3652","article-title":"A binding site for thrombin in the Apple 1 domain of factor XI","volume":"271","author":"Baglia","year":"1996","journal-title":"J Biol Chem"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m001890200","article-title":"The role of high molecular weight kininogen and prothrombin as cofactors in the binding of factor XI A3 domain to the platelet surface","volume":"275","author":"Ho","year":"2000","journal-title":"J Biol Chem"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105221200","article-title":"Characterization of the H-kininogen-binding site on factor XI","volume":"277","author":"Renn\u00e9","year":"2002","journal-title":"J Biol Chem"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.51.36373","article-title":"Identification of amino acids in the factor XI Apple 3 domain required for activation of factor IX","volume":"274","author":"Sun","year":"1999","journal-title":"J Biol Chem"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m406727200","article-title":"Identification of a binding site for glycoprotein Ib\u03b1 in the Apple 3 domain of factor XI","volume":"279","author":"Baglia","year":"2004","journal-title":"J Biol Chem"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.26.16382","article-title":"A binding site for heparin in the Apple 3 domain of factor XI","volume":"273","author":"Ho","year":"1998","journal-title":"J Biol Chem"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.47.31153","article-title":"Characterization of a heparin binding site on the heavy chain of factor XI","volume":"273","author":"Zhao","year":"1998","journal-title":"J Biol Chem"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/s0021-9258(18)53549-3","article-title":"Identification and characterization of a binding site for factor XIIa in the Apple 4 domain of coagulation factor XI","volume":"268","author":"Baglia","year":"1993","journal-title":"J Biol Chem"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m802275200","article-title":"Factor XI homodimer structure is essential for normal proteolytic activation by factor XIIa, thrombin, and factor XIa","volume":"283","author":"Wu","year":"2008","journal-title":"J Biol Chem"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03353.x","article-title":"Three residues at the interface of factor XI (FXI) monomers augment covalent dimerization of FXI","volume":"7","author":"Zucker","year":"2009","journal-title":"J Thromb Haemostasis"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.1002\/med.21503","article-title":"Recent advances in the discovery and development of factor XI\/XIa inhibitors","volume":"38","author":"Al-Horani","year":"2018","journal-title":"Med Res Rev"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.06.010","article-title":"Factor XI inhibition to uncouple thrombosis from hemostasis","volume":"78","author":"Hsu","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-10-604587","article-title":"Activated factor XI increases the procoagulant activity of the extrinsic pathway by inactivating tissue factor pathway inhibitor","volume":"125","author":"Puy","year":"2015","journal-title":"Blood"},{"key":"B29","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1160\/th14-06-0515","article-title":"Polyphosphate accelerates factor V activation by factor XIa","volume":"113","author":"Smith","year":"2017","journal-title":"Thromb Haemostasis"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2017.00232","article-title":"Removal of the C-terminal domains of ADAMTS13 by activated coagulation factor XI induces platelet adhesion on endothelial cells under flow conditions","volume":"4","author":"Garland","year":"2017","journal-title":"Front Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2016.1154045","article-title":"Factor XIa inhibitors: a review of the patent literature","volume":"26","author":"Al-Horani","year":"2016","journal-title":"Expert Opin Ther Pat"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3109\/10409238.2015.1050550","article-title":"How it all starts: initiation of the clotting cascade","volume":"50","author":"Smith","year":"2015","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2010.03899.x","article-title":"Coagulation procofactor activation by factor XIa","volume":"8","author":"Whelihan","year":"2010","journal-title":"J Thromb Haemostasis"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12435","article-title":"Evidence for factor IX\u2010independent roles for factor XIa in blood coagulation","volume":"11","author":"Matafonov","year":"2013","journal-title":"J Thromb Haemostasis"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-12-473629","article-title":"The dimeric structure of factor XI and zymogen activation","volume":"121","author":"Geng","year":"2013","journal-title":"Blood"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-200009000-00002","article-title":"Role of blood coagulation factor XI in downregulation of fibrinolysis","volume":"7","author":"Bouma","year":"2000","journal-title":"Curr Opin Hematol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/nri3345","article-title":"Thrombosis as an intravascular effector of innate immunity","volume":"13","author":"Engelmann","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.120.317447","article-title":"The emerging threat of (micro)thrombosis in COVID-19 and its therapeutic implications","volume":"127","author":"McFadyen","year":"2020","journal-title":"Circ Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04323.x","article-title":"Innate immunity and coagulation","volume":"9","author":"Esmon","year":"2011","journal-title":"J Thromb Haemostasis"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/nri1372","article-title":"Hydrophobicity: an ancient damage-associated molecular pattern that initiates innate immune responses","volume":"4","author":"Seong","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.10.012","article-title":"The immunology of sepsis","volume":"54","author":"van der Poll","year":"2021","journal-title":"Immunity"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02865.x","article-title":"Platelets, neutrophils, and neutrophil extracellular traps (NETs) in sepsis","volume":"6","author":"Ma","year":"2008","journal-title":"J Thromb Haemostasis"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-04-710632","article-title":"Disulfide HMGB1 derived from platelets coordinates venous thrombosis in mice","volume":"128","author":"Stark","year":"2016","journal-title":"Blood"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0411182","article-title":"Activated factor XI inhibits chemotaxis of polymorphonuclear leukocytes","volume":"90","author":"Itakura","year":"2011","journal-title":"J Leuk Biol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024026476","article-title":"Deficiency of neutrophil gelatinase-associated lipocalin elicits a hemophilia-like bleeding and clotting disorder in mice","volume":"145","author":"Xue","year":"2025","journal-title":"Blood"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1172\/jci116201","article-title":"The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons","volume":"91","author":"Pixley","year":"1993","journal-title":"J Clin Invest"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000398","article-title":"Cross-talk between the complement pathway and the contact activation system of coagulation: activated factor XI neutralizes complement factor H","volume":"206","author":"Puy","year":"2021","journal-title":"J Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-741298","article-title":"Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice","volume":"129","author":"Puy","year":"2017","journal-title":"Blood"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1172\/jci141374","article-title":"Complement and tissue factor\u2013enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis","volume":"130","author":"Skendros","year":"2020","journal-title":"J Clin Invest"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12715","article-title":"Novel interaction of properdin and coagulation factor XI: crosstalk between complement and coagulation","volume":"6","author":"Heal","year":"2022","journal-title":"Res Pract Thromb Haemostasis"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152968","article-title":"Factor XI deficiency alters the cytokine response and activation of contact proteases during polymicrobial sepsis in mice","volume":"11","author":"Bane","year":"2016","journal-title":"PloS One"},{"key":"B52","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1055\/s-0040-1710013","article-title":"Role of factor XIa and plasma kallikrein in arterial and venous thrombosis","volume":"120","author":"Visser","year":"2020","journal-title":"Thromb Haemost"},{"key":"B53","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1111\/jth.13194","article-title":"The contact activation and kallikrein\/kinin systems: pathophysiologic and physiologic activities","volume":"14","author":"Schmaier","year":"2016","journal-title":"J Thromb Haemost"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1613897","article-title":"High molecular weight kininogen is cleaved by FXIa at three sites: Arg409-Arg410, Lys502-Thr503 and Lys325-Lys326","volume":"83","author":"Mauron","year":"2000","journal-title":"Thromb Haemost"},{"key":"B55","doi-asserted-by":"publisher","first-page":"2258","DOI":"10.1182\/blood.v118.21.2258.2258","article-title":"Chemerin bioactivity is regulated by factor XIa: a novel interface linking between coagulation, hemostasis and immunity","volume":"118","author":"Yamaguchi","year":"2011","journal-title":"Blood"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m410291200","article-title":"Domain V of \u03b22-glycoprotein I binds factor XI\/XIa and is cleaved at Lys317-Thr318","volume":"280","author":"Shi","year":"2005","journal-title":"J Biol Chem"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-07-792580","article-title":"Prochemerin cleavage by factor XIa links coagulation and inflammation","volume":"131","author":"Ge","year":"2018","journal-title":"Blood"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03544.x","article-title":"Genetic variants associated with deep vein thrombosis: the F11 locus","volume":"7","author":"Li","year":"2009","journal-title":"J Thromb Haemostasis"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1160\/TH15-06-0459","article-title":"F11 is associated with recurrent VTE in women","volume":"115","author":"L\u00e4rfars","year":"2017","journal-title":"Thromb Haemostasis"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1111\/os.12262","article-title":"F11 rs2289252T and rs2036914C polymorphisms increase the activity of factor XI in post\u2010trauma patients with fractures despite thromboprophylaxis","volume":"8","author":"Song","year":"2016","journal-title":"Orthopaedic Surg"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1055\/s-0041-1739363","article-title":"F11 gene duplication causes elevated FXI plasma levels and is a risk for venous thrombosis","volume":"122","author":"Van Laer","year":"2021","journal-title":"Thromb Haemostasis"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-742262","article-title":"Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events","volume":"129","author":"Preis","year":"2017","journal-title":"Blood"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075286","article-title":"Genetic variants of coagulation factor XI show association with ischemic stroke up to 70 years of age","volume":"8","author":"El-Maarri","year":"2013","journal-title":"PloS One"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.118.022792","article-title":"Genetically determined FXI (factor XI) levels and risk of stroke","volume":"49","author":"Gill","year":"2018","journal-title":"Stroke"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04289.x","article-title":"Genetic variants of F11, statin use and venous thrombosis","volume":"9","author":"Bare","year":"2011","journal-title":"J Thromb Haemostasis"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2014.10.014","article-title":"Factor XI rs2036914 gene polymorphism and occurrence of adverse events after percutaneous coronary intervention. A prospective evaluation","volume":"177","author":"Campo","year":"2014","journal-title":"Int J Cardiol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1093\/ehjopen\/oeae043","article-title":"Genetic assessment of efficacy and safety profiles of coagulation cascade proteins identifies factors II and XI as actionable anticoagulant targets","volume":"4","author":"Gagnon","year":"2024","journal-title":"Eur Heart J Open"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2513880","article-title":"Asundexian for secondary stroke prevention","volume":"394","author":"Sharma","year":"2026","journal-title":"N Engl J Med"},{"key":"B69","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1056\/nejmoa2407105","article-title":"Asundexian versus apixaban in patients with atrial fibrillation","volume":"392","author":"Piccini","year":"2025","journal-title":"N Engl J Med"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15700","article-title":"Pharmacological profile of asundexian, a novel, orally bioavailable inhibitor of factor XIa","volume":"20","author":"Heitmeier","year":"2022","journal-title":"J Thromb Haemostasis"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13895","article-title":"Pharmacokinetics, pharmacodynamics, and safety of asundexian in healthy Chinese and Japanese volunteers, and comparison with Caucasian data","volume":"17","author":"Chen","year":"2024","journal-title":"Clin Transl Sci"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.122.061612","article-title":"A multicenter, phase 2, randomized, placebo-controlled, double-blind, parallel-group, dose-finding trial of the oral factor XIa inhibitor asundexian to prevent adverse cardiovascular outcomes after acute myocardial infarction","volume":"146","author":"Rao","year":"2022","journal-title":"Circulation"},{"key":"B73","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/s0140-6736(22)01588-4","article-title":"Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial","volume":"400","author":"Shoamanesh","year":"2022","journal-title":"Lancet"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1161\/str.54.suppl_1.wp177","article-title":"Abstract WP177: Effects of the oral factor XIa inhibitor asundexian on intracranial bleeding among patients with acute non-cardioembolic ischemic stroke: PACIFIC-Stroke randomized trial","volume":"54","author":"Khatri","year":"2023","journal-title":"Stroke"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1177\/17474930231216339","article-title":"Cerebral microbleeds and asundexian in non-cardioembolic ischemic stroke: secondary analyses of the PACIFIC-STROKE randomized trial","volume":"19","author":"Balali","year":"2023","journal-title":"Int J Stroke"},{"key":"B76","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1161\/strokeaha.123.043198","article-title":"Effect of the factor XIa inhibitor asundexian according to baseline infarct pattern and on MRI covert infarct outcomes","volume":"55","author":"Smith","year":"2024","journal-title":"Stroke"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(22)00456-1","article-title":"Safety of the oral factor XIa inhibitor asundexian compared with apixaban in patients with atrial fibrillation (PACIFIC-AF): a multicentre, randomised, double-blind, double-dummy, dose-finding phase 2 study","volume":"399","author":"Piccini","year":"2022","journal-title":"Lancet"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2025.0277","article-title":"Asundexian or apixaban in patients with atrial fibrillation according to prior oral anticoagulant use","volume":"10","author":"Alexander","year":"2025","journal-title":"JAMA Cardiol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1097\/cce.0000000000000196","article-title":"EP-7041, a factor XIa inhibitor as a potential antithrombotic strategy in extracorporeal membrane oxygenation: a brief report","volume":"2","author":"Pollack","year":"2020","journal-title":"Crit Care Explor"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13787","article-title":"Pharmacokinetics, pharmacodynamics, and safety of frunexian in healthy Chinese volunteer adults: a randomized dose\u2010escalation phase I study","volume":"17","author":"Zhang","year":"2024","journal-title":"Clin Transl Sci"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2025.109564","article-title":"The in vitro anticoagulant effect of milvexian in healthy neonates and children","volume":"257","author":"Letunica","year":"2025","journal-title":"Thromb Res"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00613","article-title":"Discovery of milvexian, a high-affinity, orally bioavailable inhibitor of factor XIa in clinical studies for antithrombotic therapy","volume":"65","author":"Dilger","year":"2021","journal-title":"J Med Chem"},{"key":"B83","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1111\/jth.15588","article-title":"Milvexian, an orally bioavailable, small\u2010molecule, reversible, direct inhibitor of factor XIa: in vitro studies and in vivo evaluation in experimental thrombosis in rabbits","volume":"20","author":"Wong","year":"2022","journal-title":"J Thromb Haemostasis"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.s488414","article-title":"Pharmacokinetics, pharmacodynamics, safety, and tolerability of milvexian in healthy Chinese adults","volume":"19","author":"Luo","year":"2025","journal-title":"Drug Des Dev Ther"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70058","article-title":"Absolute oral bioavailability of milvexian spray\u2010dried dispersion formulation under fasted and fed conditions in healthy adult participants: an intravenous microtracer approach","volume":"17","author":"Jarugula","year":"2024","journal-title":"Clin Transl Sci"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-022-01110-9","article-title":"Single-dose pharmacokinetics of milvexian in participants with mild or moderate hepatic impairment compared with healthy participants","volume":"61","author":"Perera","year":"2022","journal-title":"Clin Pharmacokinet"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-022-01150-1","article-title":"Single-dose pharmacokinetics of milvexian in participants with normal renal function and participants with moderate or severe renal impairment","volume":"61","author":"Perera","year":"2022","journal-title":"Clin Pharmacokinet"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac544.2704","article-title":"A randomized, cross-over study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of milvexian with single and dual antiplatelet therapy in healthy participants","volume":"43","author":"Perera","year":"2022","journal-title":"European Heart Journal"},{"key":"B89","doi-asserted-by":"publisher","first-page":"16591","DOI":"10.1038\/s41598-024-67182-8","article-title":"Safety, tolerability, pharmacokinetics and pharmacodynamics of milvexian with aspirin and\/or clopidogrel in healthy participants","volume":"14","author":"Perera","year":"2024","journal-title":"Sci Rep"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2113194","article-title":"Milvexian for the prevention of venous thromboembolism","volume":"385","author":"Weitz","year":"2021","journal-title":"N Engl J Med"},{"key":"B91","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/s1474-4422(23)00403-9","article-title":"Safety and efficacy of factor XIa inhibition with milvexian for secondary stroke prevention (AXIOMATIC-SSP): a phase 2, international, randomised, double-blind, placebo-controlled, dose-finding trial","volume":"23","author":"Sharma","year":"2024","journal-title":"Lancet Neurol"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01171","article-title":"Discovery of a parenteral small molecule coagulation factor XIa inhibitor clinical candidate (BMS-962212)","volume":"60","author":"Pinto","year":"2017","journal-title":"J Med Chem"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13520","article-title":"First\u2010in\u2010human study to assess the safety, pharmacokinetics and pharmacodynamics of BMS\u2010962212, a direct, reversible, small molecule factor XIa inhibitor in non\u2010Japanese and Japanese healthy subjects","volume":"84","author":"Perera","year":"2018","journal-title":"Br J Clin Pharmacol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.821363","article-title":"First-in-human study to assess the safety, pharmacokinetics, and pharmacodynamics of SHR2285, a small-molecule factor XIa inhibitor in healthy subjects","volume":"13","author":"Chen","year":"2022","journal-title":"Front Pharmacol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-023-01281-8","article-title":"The safety, pharmacokinetics, and pharmacodynamics of SHR2285, an oral small molecule factor XIa inhibitor, in healthy Chinese volunteers","volume":"43","author":"Xu","year":"2023","journal-title":"Clin Drug Invest"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1027627","article-title":"SHR2285, the first selectively oral FXIa inhibitor in China: safety, tolerability, pharmacokinetics and pharmacodynamics combined with aspirin, clopidogrel or ticagrelor","volume":"13","author":"Ma","year":"2022","journal-title":"Front Pharmacol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-02-900480","article-title":"MAA868 locks factor XIa in a zymogen-like state","volume":"133","author":"Weitz","year":"2019","journal-title":"Blood"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-10-880849","article-title":"MAA868, a novel FXI antibody with a unique binding mode, shows durable effects on markers of anticoagulation in humans","volume":"133","author":"Koch","year":"2019","journal-title":"Blood"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15577","article-title":"Pharmacokinetics and pharmacodynamics of abelacimab (MAA868), a novel dual inhibitor of factor XI and factor XIa","volume":"20","author":"Yi","year":"2022","journal-title":"J Thromb Haemostasis"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2105872","article-title":"Abelacimab for prevention of venous thromboembolism","volume":"385","author":"Verhamme","year":"2021","journal-title":"N Engl J Med"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2406674","article-title":"Abelacimab versus rivaroxaban in patients with atrial fibrillation","volume":"392","author":"Ruff","year":"2025","journal-title":"N Engl J Med"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.125.074037","article-title":"Abelacimab versus rivaroxaban in patients with atrial fibrillation on antiplatelet therapy: A prespecified analysis of the AZALEA-TIMI 71 trial","volume":"152","author":"Al Said","year":"2025","journal-title":"Circulation"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2025.02.013","article-title":"Factor XI\/XIa inhibitors versus direct oral anticoagulants in atrial fibrillation","volume":"137","author":"Zeng","year":"2025","journal-title":"Eur J Internal Med"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.09.008","article-title":"Allosteric inhibition as a new mode of action for BAY 1213790, a neutralizing antibody targeting the activated form of coagulation factor XI","volume":"431","author":"Schaefer","year":"2019","journal-title":"J Mol Biol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpth.2025.102932","article-title":"The factor XIa antibody osocimab strongly inhibits clotting in extracorporeal circuits with human blood and in baboons","volume":"9","author":"Samaha","year":"2025","journal-title":"Res Pract Thromb Haemost"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12186","article-title":"BAY 1213790, a fully human IgG1 antibody targeting coagulation factor XIa: First evaluation of safety, pharmacodynamics, and pharmacokinetics","volume":"3","author":"Thomas","year":"2019","journal-title":"Res Pract Thromb Haemostasis"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.20687","article-title":"Effect of osocimab in preventing venous thromboembolism among patients undergoing knee arthroplasty","volume":"323","author":"Weitz","year":"2020","journal-title":"Jama"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02794-7","article-title":"Anticoagulation with osocimab in patients with kidney failure undergoing hemodialysis: A randomized phase 2 trial","volume":"30","author":"Weitz","year":"2024","journal-title":"Nat Med"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-012-0186-5","article-title":"Inhibition of factor XII-mediated activation of factor XI provides protection against experimental acute ischemic stroke in mice","volume":"3","author":"Leung","year":"2012","journal-title":"Trans Stroke Res"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-270918","article-title":"A role for factor XIIa\u2013mediated factor XI activation in thrombus formation in vivo","volume":"116","author":"Cheng","year":"2010","journal-title":"Blood"},{"key":"B111","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1161\/atvbaha.118.312328","article-title":"Contact activation inhibitor and factor XI antibody, AB023, produces safe, dose-dependent anticoagulation in a phase 1 first-in-human trial","volume":"39","author":"Lorentz","year":"2019","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-139948","article-title":"Safety and efficacy of the contact activation inhibitor AB023 in patients with end-stage renal disease on chronic hemodialysis: A phase 2, double-blind, randomized, placebo-controlled trial","volume":"136","author":"Lorentz","year":"2020","journal-title":"Blood"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.123.319692","article-title":"Factor XI inhibition for the prevention of catheter-associated thrombosis in patients with cancer undergoing central line placement: A phase 2 clinical trial","volume":"44","author":"Pfeffer","year":"2024","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2024.2391837","article-title":"The first-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the factor XI monoclonal antibody SHR-2004 in healthy subjects","volume":"33","author":"Ma","year":"2024","journal-title":"Expert Opin Invest Drugs"},{"key":"B115","article-title":"Abstract LB 01.2","author":"Xiao","year":"2026"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15744","article-title":"First randomized evaluation of safety, pharmacodynamics, and pharmacokinetics of BAY 1831865, an antibody targeting coagulation factor XI and factor XIa, in healthy men","volume":"20","author":"Nowotny","year":"2022","journal-title":"J Thromb Haemostasis"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1002\/bcp.70043","article-title":"Pharmacokinetics, pharmacodynamics and safety profile of SKB336, a selective inhibitor of coagulation factor XI\/XIa in healthy subjects","volume":"91","author":"Xiang","year":"2025","journal-title":"Br J Clin Pharmacol"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpth.2023.100067","article-title":"BJTJ-1837, a novel FXI activation-blocking antibody","volume":"7","author":"He","year":"2023","journal-title":"Res Pract Thromb Haemostasis"},{"key":"B119","doi-asserted-by":"publisher","first-page":"3076","DOI":"10.1182\/blood.v112.11.3076.3076","article-title":"Antithrombotic effects of a FXI antisense oligonucleotide in mice","volume":"112","author":"Monia","year":"2008","journal-title":"Blood"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-277798","article-title":"Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: a novel antithrombotic strategy with lowered bleeding risk","volume":"116","author":"Zhang","year":"2010","journal-title":"Blood"},{"key":"B121","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.1182\/blood.v118.21.2255.2255","article-title":"ISIS-FXIRx, a potent antisense inhibitor of factor XI, suppresses FXI activity and elevates Aptt without increased risk of bleeding in cynomolgus monkeys following 13 weeks of treatment","volume":"118","author":"Younis","year":"2011","journal-title":"Blood"},{"key":"B122","doi-asserted-by":"publisher","first-page":"2250","DOI":"10.1182\/blood.v118.21.2250.2250","article-title":"Antisense oligonucleotide mediated depletion of factor XI prevents vascular occlusion in an experimental thrombosis model in primates","volume":"118","author":"Crosby","year":"2011","journal-title":"Blood"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-12-540872","article-title":"Selective depletion of factor XI or factor XII with antisense oligonucleotides attenuates catheter thrombosis in rabbits","volume":"123","author":"Yau","year":"2014","journal-title":"Blood"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2021.11.011","article-title":"Phase 2 study of the factor XI antisense inhibitor IONIS-FXIRx in patients with ESRD","volume":"7","author":"Walsh","year":"2022","journal-title":"Kidney Int Rep"},{"key":"B125","article-title":"IONIS-FXI-LRx, an FXI GalNAc-conjugated antisense drug, produces potent and sustained reduction in FXI activity in normal volunteers","author":"Bethune","year":""},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13784","article-title":"Pharmacokinetics, pharmacodynamics, and safety of fesomersen, a novel antisense inhibitor of factor XI, in healthy Chinese, Japanese, and Caucasian volunteers","volume":"17","author":"Liu","year":"2024","journal-title":"Clin Transl Sci"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2024.02.024","article-title":"A phase II randomized controlled trial evaluated antithrombotic treatment with fesomersen in patients with kidney failure on hemodialysis","volume":"106","author":"Winkelmayer","year":"2024","journal-title":"Kidney Int"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2024.12.005","article-title":"Inhibition of factor XI using RBD4059","volume":"10","author":"Liang","year":"2025","journal-title":"JACC: Basic to Trans Sci"},{"key":"B129","doi-asserted-by":"publisher","first-page":"4009","DOI":"10.1182\/blood-2024-203718","article-title":"A phase 1, single ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of subcutaneously administered SRSD107 in healthy subjects","volume":"144","author":"Yue","year":"2024","journal-title":"Blood"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0013282","article-title":"Functional characterization of a common XIa inhibitory Kunitz-domain Shp4 from nine schistosoma secreted proteins with diverse C-terminal fragments","volume":"19","author":"Ye","year":"2025","journal-title":"PloS Negl Trop Dis"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1126\/science.2111585","article-title":"Platelet coagulation factor XI a -inhibitor, a form of Alzheimer amyloid precursor protein","volume":"248","author":"Smith","year":"1990","journal-title":"Science"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-419523","article-title":"The kunitz protease inhibitor domain of protease nexin-2 inhibits factor XIa and murine carotid artery and middle cerebral artery thrombosis","volume":"120","author":"Wu","year":"2012","journal-title":"Blood"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10071679","article-title":"A factor XIa inhibitor engineered from banded krait venom toxin: Efficacy and safety in rodent models of arterial and venous thrombosis","volume":"10","author":"Chng","year":"2022","journal-title":"Biomedicines"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106951","article-title":"Design, expression and biological evaluation of DX-88mut as a novel selective factor XIa inhibitor for antithrombosis","volume":"142","author":"Sun","year":"2024","journal-title":"Bioorg Chem"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2024.117067","article-title":"Discovery of potent and selective factor XIa inhibitors incorporating triazole-based benzoic acid as novel P2\u2019 fragments: Molecular dynamics simulations and anticoagulant activity","volume":"282","author":"Dai","year":"2025","journal-title":"Eur J Med Chem"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117436","article-title":"Discovery of potent, highly selective, and orally bioavailable factor XIa inhibitors for anticoagulant therapy","volume":"289","author":"Zhang","year":"2025","journal-title":"Eur J Med Chem"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.118457","article-title":"Design, synthesis and biological evaluation of novel FXIa inhibitors featuring five-membered heterocycles as P2\u2019 fragments","volume":"303","author":"Wu","year":"2026","journal-title":"Eur J Med Chem"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.116.306925","article-title":"Factor XI as a therapeutic target","volume":"36","author":"Gailani","year":"2016","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0b013e328309ec85","article-title":"Novel roles for factor XII-driven plasma contact activation system","volume":"15","author":"Muller","year":"2008","journal-title":"Curr Opin Hematol"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15439","article-title":"First evaluation of the safety, pharmacokinetics, and pharmacodynamics of BAY 2433334, a small molecule targeting coagulation factor XIa","volume":"19","author":"Thomas","year":"2021","journal-title":"J Thromb Haemost"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15981","article-title":"Pharmacokinetics of asundexian with combined CYP3A and P-gp inhibitors and an inducer: Target in vitro and in vivo studies","volume":"90","author":"Kanefendt","year":"2024","journal-title":"Br J Clin Pharmacol"},{"key":"B142","doi-asserted-by":"publisher","first-page":"22239","DOI":"10.1038\/s41598-022-25936-2","article-title":"Effects of rifampin on the pharmacokinetics and pharmacodynamics of milvexian, a potent, selective, oral small molecule factor XIa inhibitor","volume":"12","author":"Perera","year":"2022","journal-title":"Sci Rep"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2025.02.025","article-title":"Anticoagulant drugs targeting factor XI\/XIa and coagulation tests: We urgently need reliable pharmacodynamic data","volume":"23","author":"Gouin-Thibault","year":"2025","journal-title":"J Thromb Haemost"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.3390\/hematolrep16010016","article-title":"Drug-drug interactions of FXI inhibitors: Clinical relevance","volume":"16","author":"Ferri","year":"2024","journal-title":"Hematol Rep"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-024-02972-5","article-title":"Factor XI: Structure, function and therapeutic inhibition","volume":"57","author":"Ali","year":"2024","journal-title":"J Thromb Thromb"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2023.151484","article-title":"Factor XI inhibitors: Potential role in end-stage kidney disease","volume":"43","author":"Ades","year":"2023","journal-title":"Semin Nephrol"},{"key":"B147","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1038\/s41419-022-05075-2","article-title":"RNA-based therapeutics: An overview and prospectus","volume":"13","author":"Zhu","year":"2022","journal-title":"Cell Death Dis"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00162-z","article-title":"Antisense technology: An overview and prospectus","volume":"20","author":"Crooke","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"B149","doi-asserted-by":"publisher","first-page":"15006","DOI":"10.1038\/nrdp.2015.6","article-title":"Venous thrombosis","volume":"1","author":"Wolberg","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2009.07.002","article-title":"Basic mechanisms and pathogenesis of venous thrombosis","volume":"23","author":"Esmon","year":"2009","journal-title":"Blood Rev"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1172\/jci60229","article-title":"New insights into the mechanisms of venous thrombosis","volume":"122","author":"Mackman","year":"2012","journal-title":"J Clin Invest"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2018.04.010","article-title":"Immune factors in deep vein thrombosis initiation","volume":"39","author":"Budnik","year":"2018","journal-title":"Trends Immunol"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112322","article-title":"Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo","volume":"209","author":"von Bruhl","year":"2012","journal-title":"J Exp Med"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005743107","article-title":"Extracellular DNA traps promote thrombosis","volume":"107","author":"Fuchs","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2015.83","article-title":"Epidemiology of venous thromboembolism","volume":"12","author":"Heit","year":"2015","journal-title":"Nat Rev Cardiol"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.1111\/pin.12921","article-title":"Pathophysiology of atherothrombosis: Mechanisms of thrombus formation on disrupted atherosclerotic plaques","volume":"70","author":"Asada","year":"2020","journal-title":"Pathol Int"},{"key":"B157","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/pin.13305","article-title":"Underlying mechanisms of thrombus formation\/growth in atherothrombosis and deep vein thrombosis","volume":"73","author":"Yamashita","year":"2023","journal-title":"Pathol Int"},{"key":"B158","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1007\/s11883-012-0269-5","article-title":"Role of tissue factor in atherothrombosis","volume":"14","author":"Owens","year":"2012","journal-title":"Curr Atheroscler Rep"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12080","article-title":"The coagulation system in atherothrombosis: Implications for new therapeutic strategies","volume":"2","author":"Olie","year":"2018","journal-title":"Res Pract Thromb Haemost"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.1161\/cir.0000000000001309","article-title":"2025 ACC\/AHA\/ACEP\/NAEMSP\/SCAI guideline for the management of patients with acute coronary syndromes: A report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"151","author":"Rao","year":"2025","journal-title":"Circulation"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1161\/str.0000000000000375","article-title":"2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: A guideline from the American Heart Association\/American Stroke Association","volume":"52","author":"Kleindorfer","year":"2021","journal-title":"Stroke"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.125.054846","article-title":"Antithrombotic therapy for noncardioembolic ischemic stroke: Current evidence and future directions","volume":"57","author":"Cucchiara","year":"2026","journal-title":"Stroke"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.82.5.547","article-title":"Left atrial appendage: structure, function, and role in thromboembolism","volume":"82","author":"Al-Saady","year":"1999","journal-title":"Heart"},{"key":"B164","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2020-316977","article-title":"Atrial fibrillation and the prothrombotic state: Revisiting Virchow's triad in 2020","volume":"106","author":"Ding","year":"2020","journal-title":"Heart"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.116.013105","article-title":"Thrombus histology suggests cardioembolic cause in cryptogenic stroke","volume":"47","author":"Boeckh-Behrens","year":"2016","journal-title":"Stroke"},{"key":"B166","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41572-022-00336-y","article-title":"Cancer-associated venous thromboembolism","volume":"8","author":"Khorana","year":"2022","journal-title":"Nat Rev Dis Primers"},{"key":"B167","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s12185-024-03735-x","article-title":"The pathogenesis of cancer-associated thrombosis","volume":"119","author":"Tatsumi","year":"2024","journal-title":"Int J Hematol"},{"key":"B168","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11216314","article-title":"Clinical pharmacology of factor XI inhibitors: New therapeutic approaches for prevention of venous and arterial thrombotic disorders","volume":"11","author":"Campello","year":"2022","journal-title":"J Clin Med"},{"key":"B169","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad655.2833","article-title":"Factor XI inhibitors in early clinical trials: A meta-analysis","volume":"123","author":"Galli","year":"2023","journal-title":"Thromb Haemostasis"},{"key":"B170","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01948","article-title":"Comprehensive structure\u2013activity relationship of triantennaryN-acetylgalactosamine conjugated antisense oligonucleotides for targeted delivery to hepatocytes","volume":"59","author":"Prakash","year":"2016","journal-title":"J Med Chem"},{"key":"B171","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab047","article-title":"Site-specific incorporation of 5\u2032-methyl DNA enhances the therapeutic profile of gapmer ASOs","volume":"49","author":"Vasquez","year":"2021","journal-title":"Nucleic Acids Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1925585\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:39:41Z","timestamp":1791196781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1925585\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":171,"alternative-id":["10.3389\/fimmu.2026.1925585"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1925585","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"article-number":"1925585"}}