{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:26:26Z","timestamp":1791584786446,"version":"4.3.4"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Thrombosis J"],"DOI":"10.1186\/s12959-025-00807-8","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T10:34:16Z","timestamp":1763807656000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Asundexian: a systematic review of safety, efficacy, and pharmacological insights in thrombosis"],"prefix":"10.1186","volume":"23","author":[{"given":"Ziad Sad","family":"Aldeen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawaf","family":"Al-Hashemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Kokori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Aderinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gbolahan","family":"Olatunji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Gaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahmon","family":"Moradeyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hafeez","family":"Shaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,22]]},"reference":[{"issue":"8","key":"807_CR1","doi-asserted-by":"publisher","first-page":"e41","DOI":"10.1161\/CIR.0000000000001303","volume":"151","author":"SS Martin","year":"2025","unstructured":"Martin SS, Aday AW, Allen NB, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, Baker-Smith CM, Bansal N, Beaton AZ, Commodore-Mensah Y, Currie ME, Elkind MSV, Fan W, Generoso G, Gibbs BB, Heard DG, Hiremath S, Johansen MC, Kazi DS, Ko D, Leppert MH, Magnani JW, Michos ED, Mussolino ME, Parikh NI, Perman SM, Rezk-Hanna M, Roth GA, Shah NS, Springer MV, St-Onge MP, Thacker EL, Urbut SM, Van Spall HGC, Voeks JH, Whelton SP, Wong ND, Wong SS, Yaffe K, Palaniappan LP, American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Committee. 2025 heart disease and stroke statistics: A report of US and global data from the American Heart Association. Circulation. 2025;151(8):e41\u2013660. https:\/\/doi.org\/10.1161\/CIR.0000000000001303. Epub 2025 Jan 27. PMID: 39866113.","journal-title":"Circulation"},{"key":"807_CR2","doi-asserted-by":"crossref","unstructured":"Mosevoll KA, Johansen S, Wendelbo \u00d8, Nepstad I, Bruserud \u00d8, Reikvam H. Cytokines, adhesion molecules, and matrix metalloproteases as predisposing, diagnostic, and prognostic factors in venous thrombosis. Front Med. 2018;5.","DOI":"10.3389\/fmed.2018.00147"},{"issue":"1","key":"807_CR3","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s00281-011-0285-5","volume":"34","author":"VWM \u200cvan Hinsbergh","year":"2011","unstructured":"\u200cvan Hinsbergh VWM. Endothelium\u2014role in regulation of coagulation and inflammation. Semin Immunopathol. 2011;34(1):93\u2013106.","journal-title":"Semin Immunopathol"},{"key":"807_CR4","doi-asserted-by":"crossref","unstructured":"\u200cBucciarelli P, Rosendaal FR, Tripodi A, Pier Mannuccio Mannucci, De Stefano V, Gualtiero P, et al., Risk of venous thromboembolism and clinical manifestations in carriers of antithrombin, protein C, protein S deficiency, or activated protein C resistance. Arterioscler Thromb Vasc Biol. 1999;19(4):1026\u201333.","DOI":"10.1161\/01.ATV.19.4.1026"},{"issue":"1","key":"807_CR5","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.transci.2007.12.005","volume":"38","author":"AS \u200cWolberg","year":"2008","unstructured":"\u200cWolberg AS, Campbell RA. Thrombin generation, fibrin clot formation and hemostasis. Transfus Apheres Sci. 2008;38(1):15\u201323.","journal-title":"Transfus Apheres Sci"},{"issue":"7181","key":"807_CR6","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1038\/nature06797","volume":"451","author":"N Mackman","year":"2008","unstructured":"Mackman N, Triggers. Targets and treatments for thrombosis. Nature. 2008;451(7181):914\u20138.","journal-title":"Nature"},{"issue":"1","key":"807_CR7","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1007\/s11239-015-1317-0","volume":"41","author":"MB \u200cStreiff","year":"2016","unstructured":"\u200cStreiff MB, Agnelli G, Connors JM, Crowther M, Eichinger S, Lopes R, et al. Guidance for the treatment of deep vein thrombosis and pulmonary embolism. J Thromb Thrombolysis. 2016;41(1):32\u201367.","journal-title":"J Thromb Thrombolysis"},{"key":"807_CR8","doi-asserted-by":"crossref","unstructured":"Bortman LV, Mitchell F, Naveiro S, Juana P\u00e9rez Morales, Gonzalez C, Guillermo DG, et al. Direct oral anticoagulants: an updated systematic review of their clinical Pharmacology and clinical effectiveness and safety in patients with nonvalvular atrial fibrillation. 2022.","DOI":"10.1002\/jcph.2184"},{"key":"807_CR9","doi-asserted-by":"publisher","unstructured":"Bejjani A, Khairani CD, Assi A, Piazza G, Sadeghipour P, Talasaz AH, Fanikos J, Connors JM, Siegal DM, Barnes GD, Martin KA, Angiolillo DJ, Kleindorfer D, Monreal M, Jimenez D, Middeldorp S, Elkind MSV, Ruff CT, Goldhaber SZ, Krumholz HM, Mehran R, Cushman M, Eikelboom JW, Lip GYH, Weitz JI, Lopes RD, Bikdeli B. When direct oral anticoagulants should not be standard treatment: JACC State-of-the-art review. J Am Coll Cardiol. 2024;83(3):444\u2013465. https:\/\/doi.org\/10.1016\/j.jacc.2023.10.038. Erratum in: J Am Coll Cardiol. 2024;83(14):1351. https:\/\/doi.org\/10.1016\/j.jacc.2024.02.032. PMID: 38233019.","DOI":"10.1016\/j.jacc.2023.10.038"},{"key":"807_CR10","doi-asserted-by":"crossref","unstructured":"Catterall F, Ames PR, Isles C. Warfarin in patients with mechanical heart valves. BMJ. 2020;m3956.","DOI":"10.1136\/bmj.m3956"},{"issue":"1","key":"807_CR11","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.hest.2020.01.001","volume":"1","author":"A \u200cMorotti","year":"2020","unstructured":"\u200cMorotti A, Goldstein JN. Anticoagulant-associated intracerebral hemorrhage. Brain Hemorrhages. 2020;1(1):89\u201394.","journal-title":"Brain Hemorrhages"},{"issue":"4","key":"807_CR12","doi-asserted-by":"publisher","first-page":"314","DOI":"10.7861\/clinmedicine.18-4-314","volume":"18","author":"S \u200cThomas","year":"2018","unstructured":"\u200cThomas S, Makris M. The reversal of anticoagulation in clinical practice. Clin Med. 2018;18(4):314\u20139.","journal-title":"Clin Med"},{"issue":"10","key":"807_CR13","doi-asserted-by":"publisher","first-page":"477","DOI":"10.2217\/fca-2023-0051","volume":"19","author":"DA \u200cNicasia","year":"2023","unstructured":"\u200cNicasia DA, Cave B, Hough A. Asundexian: an oral small molecule factor XIa inhibitor for the treatment of thrombotic disorders. Future Cardiol. 2023;19(10):477\u201386.","journal-title":"Future Cardiol"},{"issue":"2","key":"807_CR14","first-page":"69","volume":"48","author":"NK Bentounes","year":"2023","unstructured":"Bentounes NK, Melicine S, Martin AC, Smadja DM, Gendron N. Development of new anticoagulant in 2023: prime time for anti-factor XI and XIa inhibitors. J Med Vasc. 2023;48(2):69\u201380. Epub 2023 May 5. PMID: 37422330.","journal-title":"J Med Vasc"},{"issue":"3","key":"807_CR15","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1002\/cpdd.1366","volume":"13","author":"C \u200bBrase","year":"2024","unstructured":"\u200bBrase C, Kanefendt F, Loewen S, Himmel H, Schmitz S. No influence of asundexian on cardiac repolarization. Clin Pharmacol Drug Dev. 2024;13(3):265\u201380.","journal-title":"Clin Pharmacol Drug Dev"},{"key":"807_CR16","doi-asserted-by":"crossref","unstructured":"Piccini JP, Patel MR, Steffel J, Ferdinand K, Van Gelder IC, Russo AM, et al. Asundexian versus apixaban in patients with atrial fibrillation. N Engl J Med. 2024;23\u201332.","DOI":"10.1056\/NEJMoa2407105"},{"issue":"7","key":"807_CR17","doi-asserted-by":"publisher","first-page":"3447","DOI":"10.1111\/bcp.15230","volume":"88","author":"D \u200bKubitza","year":"2022","unstructured":"\u200bKubitza D, Heckmann M, Distler J, Koechel A, Schwers S, Kanefendt F. Pharmacokinetics, pharmacodynamics and safety of BAY 2433334, a novel activated factor XI inhibitor, in healthy volunteers: A randomized phase 1 multiple-dose study. Br J Clin Pharmacol. 2022;88(7):3447\u201362.","journal-title":"Br J Clin Pharmacol"},{"issue":"2","key":"807_CR18","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1002\/cpdd.1207","volume":"12","author":"F Kanefendt","year":"2023","unstructured":"Kanefendt F, Brase C, Unger S, Kubitza D. Effects of tablet Formulation, Food, or gastric pH on the bioavailability of asundexian. Clin Pharmacol Drug Dev. 2023;12(2):219\u201330.","journal-title":"Clin Pharmacol Drug Dev"},{"issue":"8","key":"807_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/cts.13895","volume":"17","author":"H Chen","year":"2024","unstructured":"Chen H, Hashizume K, Kanefendt F, Brase C, Schmitz S, Liu T. Pharmacokinetics, pharmacodynamics, and safety of asundexian in healthy Chinese and Japanese volunteers, and comparison with Caucasian data. Clin Transl Sci. 2024;17(8):1\u201313.","journal-title":"Clin Transl Sci"},{"issue":"10333","key":"807_CR20","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1016\/S0140-6736(22)00456-1","volume":"399","author":"JP Piccini","year":"2022","unstructured":"Piccini JP, Caso V, Connolly SJ, Fox KAA, Oldgren J, Jones WS, et al. 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. Lancet. 2022;399(10333):1383\u201390.","journal-title":"Lancet"},{"key":"807_CR21","doi-asserted-by":"publisher","unstructured":"Shoamanesh A, Mundl H, Smith EE, Masjuan J, Milanov I, Hirano T, et al. Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial. Lancet [Internet]. 2022;400(10357):997\u20131007. Available from: https:\/\/doi.org\/10.1016\/S0140-6736(22)01588-4","DOI":"10.1016\/S0140-6736(22)01588-4"},{"issue":"2","key":"807_CR22","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1161\/STROKEAHA.123.043198","volume":"55","author":"EE Smith","year":"2024","unstructured":"Smith EE, Shoamanesh A, Xu L, Heenan L, Saad F, Colorado P, et al. Effect of the factor XIa inhibitor asundexian according to baseline infarct pattern and on MRI Covert infarct outcomes. Stroke. 2024;55(2):392\u2013402.","journal-title":"Stroke"},{"issue":"16","key":"807_CR23","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1161\/CIRCULATIONAHA.122.061612","volume":"146","author":"SV Rao","year":"2022","unstructured":"Rao SV, Kirsch B, Bhatt DL, Budaj A, Coppolecchia R, Eikelboom J, et al. 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. Circulation. 2022;146(16):1196\u2013206.","journal-title":"Circulation"},{"issue":"10","key":"807_CR24","doi-asserted-by":"publisher","first-page":"2407","DOI":"10.1111\/jth.15439","volume":"19","author":"D \u200bThomas","year":"2021","unstructured":"\u200bThomas D, Kanefendt F, 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. J Thromb Haemost. 2021;19(10):2407\u201316.","journal-title":"J Thromb Haemost"},{"issue":"5","key":"807_CR25","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1177\/17474930231216339","volume":"19","author":"P Balali","year":"2024","unstructured":"Balali P, Hart RG, Smith EE, Saad F, Colorado P, Lemmens R, et al. Cerebral microbleeds and asundexian in non-cardioembolic ischemic stroke: secondary analyses of the PACIFIC-STROKE randomized trial. Int J Stroke. 2024;19(5):526\u201335.","journal-title":"Int J Stroke"},{"issue":"6","key":"807_CR26","doi-asserted-by":"publisher","first-page":"3346","DOI":"10.3390\/ijms23063346","volume":"23","author":"JR Olaetxea","year":"2022","unstructured":"Olaetxea JR, Alloza I, Vandenbroeck K, Mart\u00edn C. Pathophysiology of atherosclerosis. Int J Mol Sci. 2022;23(6):3346. https:\/\/doi.org\/10.3390\/ijms23063346.","journal-title":"Int J Mol Sci"},{"key":"807_CR27","doi-asserted-by":"publisher","first-page":"100179","DOI":"10.1016\/j.crphar.2024.100179","volume":"6","author":"HA Badreldin","year":"2024","unstructured":"Badreldin HA, Alsuhebany N, Alzahrani M, Alshehri AM, Aldoughaim M, Alqifari S, Yassin O, Alfehaid L, Alqahtani T. Abelacimab: A leap forward in anticoagulation with FXI and FXIa Inhibition. Curr Res Pharmacol Drug Discovery. 2024;6:100179. https:\/\/doi.org\/10.1016\/j.crphar.2024.100179.","journal-title":"Curr Res Pharmacol Drug Discovery"},{"issue":"3","key":"807_CR28","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.jtha.2022.11.029","volume":"21","author":"JR Shaw","year":"2023","unstructured":"Shaw JR, Castellucci LA, Siegal D, Carrier M. DOAC\u2013associated bleeding, hemostatic strategies, and thrombin generation assays - a review of the literature. J Thromb Haemost. 2023;21(3):433\u201352. https:\/\/doi.org\/10.1016\/j.jtha.2022.11.029.","journal-title":"J Thromb Haemost"},{"issue":"3","key":"807_CR29","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.jtha.2022.10.005","volume":"21","author":"SE Reitsma","year":"2023","unstructured":"Reitsma SE, Holle LA, Bouck EG, Monroe DM, Mast AE, Burthem J, Bolton-Maggs PHB, Gidley GN, Wolberg AS. Tissue factor pathway inhibitor is a potential modifier of bleeding risk in factor XI deficiency. J Thromb Haemost. 2023;21(3):467\u201379. Epub 2022 Dec 22. PMID: 36696199; PMCID: PMC10111213.","journal-title":"J Thromb Haemost"},{"issue":"1","key":"807_CR30","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.jtha.2024.10.019","volume":"23","author":"B Samuelson Bannow","year":"2025","unstructured":"Samuelson Bannow B, Edelman A, Carrier M. D\u00e9j\u00e0 Vu all over again: a recurrent flaw in anticoagulant study design. J Thromb Haemost. 2025;23(1):23\u20136. https:\/\/doi.org\/10.1016\/j.jtha.2024.10.019. Epub 2024 Oct 28. PMID: 39476970; PMCID: PMC11725431.","journal-title":"J Thromb Haemost"},{"issue":"2","key":"807_CR31","doi-asserted-by":"publisher","first-page":"100072","DOI":"10.1016\/j.rpth.2023.100072","volume":"7","author":"JP Patel","year":"2023","unstructured":"Patel JP, Nzelu O, Roberts LN, Johns J, Ross J, Arya R. How do anticoagulants impact menstrual bleeding and quality of life? - The PERIOD study. Res Pract Thromb Haemostasis. 2023;7(2):100072. https:\/\/doi.org\/10.1016\/j.rpth.2023.100072.","journal-title":"Res Pract Thromb Haemostasis"},{"issue":"3","key":"807_CR32","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.4022\/jafib.1112","volume":"7","author":"F Violi","year":"2014","unstructured":"Violi F, Pastori D, Pignatelli P. Mechanisms and management of Thrombo-Embolism in atrial fibrillation. J Atr Fibrillation. 2014;7(3):1112. https:\/\/doi.org\/10.4022\/jafib.1112.","journal-title":"J Atr Fibrillation"},{"key":"807_CR33","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.ahj.2024.08.011","volume":"277","author":"SS Jain","year":"2024","unstructured":"Jain SS, Mahaffey KW, Pieper KS, Shimizu W, Potpara T, Ruff CT, Kamel H, Lewis BS, Cornel JH, Kowey PR, Horrow J, Strony J, Plotnikov AN, Li D, Weng S, Donahue J, Gibson CM, Steg PG, Mehran R, Lam CS. Milvexian vs Apixaban for stroke prevention in atrial fibrillation: the LIBREXIA atrial fibrillation trial rationale and design. Am Heart J. 2024;277:145\u201358. https:\/\/doi.org\/10.1016\/j.ahj.2024.08.011.","journal-title":"Am Heart J"},{"issue":"14","key":"807_CR34","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1056\/NEJMoa1709118","volume":"377","author":"JW Eikelboom","year":"2017","unstructured":"Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, Diaz R, Alings M, Lonn EM, Anand SS, Widimsky P, Hori M, Avezum A, Piegas LS, Branch KRH, Probstfield J, Bhatt DL, Zhu J, Liang Y, Maggioni AP, Lopez-Jaramillo P, O\u2019Donnell M, Kakkar AK, Fox KAA, Parkhomenko AN, Ertl G, St\u00f6rk S, Keltai M, Ryden L, Pogosova N, Dans AL, Lanas F, Commerford PJ, Torp-Pedersen C, Guzik TJ, Verhamme PB, Vinereanu D, Kim JH, Tonkin AM, Lewis BS, Felix C, Yusoff K, Steg PG, Metsarinne KP, Cook Bruns N, Misselwitz F, Chen E, Leong D, Yusuf S. COMPASS Investigators. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377(14):1319\u201330. https:\/\/doi.org\/10.1056\/NEJMoa1709118. Epub 2017 Aug 27. PMID: 28844192.","journal-title":"N Engl J Med"}],"container-title":["Thrombosis Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12959-025-00807-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12959-025-00807-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12959-025-00807-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T10:01:18Z","timestamp":1763978478000},"score":1,"resource":{"primary":{"URL":"https:\/\/thrombosisjournal.biomedcentral.com\/articles\/10.1186\/s12959-025-00807-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,22]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["807"],"URL":"https:\/\/doi.org\/10.1186\/s12959-025-00807-8","relation":{},"ISSN":["1477-9560"],"issn-type":[{"value":"1477-9560","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,22]]},"assertion":[{"value":"19 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"114"}}