{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:35:53Z","timestamp":1772778953442,"version":"3.50.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Atraumatic splenic rupture (ASR), though rare, is an adverse event linked to direct oral anticoagulants (DOACs). Given their widespread use and potentially fatal consequences if undiagnosed, heightened clinical awareness of DOAC-associated ASR is crucial. Our aim was to analyze the occurrence and clinical characteristics of ASR induced by DOACs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective analysis of all reported DOAC-associated ASR cases through 15 April 2025, without language restrictions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 27 patients (11 males and 16 females) were included with a median age of 64\u00a0years. Among them, apixaban (n = 17) was the most common DOAC, followed by rivaroxaban (n = 8) and dabigatran (n = 2), with atrial fibrillation (81.5%, n = 22) being the primary indication. The comorbidities observed among patients with DOAC-associated ASR risk included hypertension (25.9%), coronary heart disease (18.5%), malignancy (18.5%), and infections (18.5%). Among 27 patients, 11 (40.7%) received concomitant medications that may potentiate DOAC effects, with 5 patients taking four interacting drugs simultaneously. Only 4 of the 11 patients had documented anticoagulant dosages, half of which were full-dose regimens. Management included immediate DOAC cessation (100.0%), transfusion (77.8%), splenic artery embolization (44.4%), and splenectomy (70.4%) \u2013 with 31.6% of splenectomies representing salvage procedures following failed embolization. All patients were successfully discharged with no mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ASR is a potentially life-threatening but preventable DOAC complication. Early recognition\u2014particularly in elderly patients with comorbidities and polypharmacy\u2014and urgent imaging for abdominal pain are crucial for improving clinical outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1777780","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:30:53Z","timestamp":1772775053000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of the clinical characteristics of direct oral anticoagulants-associated atraumatic splenic rupture"],"prefix":"10.3389","volume":"17","author":[{"given":"Can","family":"Shi","sequence":"first","affiliation":[{"name":"Third Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"Third Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Third Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren","family":"Guo","sequence":"additional","affiliation":[{"name":"Third Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Wu","sequence":"additional","affiliation":[{"name":"Third Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"B1","first-page":"792","article-title":"Apixaban-associated spontaneous splenic rupture-a case report","volume":"111","author":"Abdelhady","year":"2018","journal-title":"Ir. Med. J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"S998","DOI":"10.14309\/01.ajg.0000782920.27020.88","article-title":"Spontaneous ruptured splenic artery aneurysm presenting as an acute abdominal mass","volume":"116","author":"Abdulrahman","year":"2021","journal-title":"Am. J. Gastroenterol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1056\/NEJMoa1302507","article-title":"Oral apixaban for the treatment of acute venous thromboembolism","volume":"369","author":"Agnelli","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e7805","DOI":"10.7759\/cureus.7805","article-title":"A delayed splenic tragedy beyond the scope of a colonoscope: a rare find","volume":"12","author":"Ahmed","year":"2020","journal-title":"Cureus"},{"key":"B5","article-title":"Splenic rupture","volume-title":"StatPearls","author":"Akoury","year":"2025"},{"key":"B6","doi-asserted-by":"crossref","first-page":"E54","DOI":"10.1177\/000313481608200208","article-title":"Hemorrhagic shock from spontaneous splenic rupture requiring open splenectomy in a patient taking rivaroxaban","volume":"82","author":"Amin","year":"2016","journal-title":"Am. Surg."},{"key":"B7","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1471-227X-12-11","article-title":"613 cases of splenic rupture without risk factors or previously diagnosed disease: a systematic review","volume":"12","author":"Aubrey-Bassler","year":"2012","journal-title":"BMC Emerg. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"84","DOI":"10.55729\/2000-9666.1098","article-title":"Atraumatic splenic rupture on direct oral anticoagulation","volume":"12","author":"Barnes","year":"2022","journal-title":"J. Community Hosp. Intern Med. Perspect."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2050313X19832490","DOI":"10.1177\/2050313X19832490","article-title":"Atraumatic splenic rupture associated with apixaban","volume":"7","author":"Basnet","year":"2019","journal-title":"SAGE Open Med. Case Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e67512","DOI":"10.7759\/cureus.67512","article-title":"A case of spontaneous splenic rupture after a hemicolectomy on anticoagulation","volume":"16","author":"Bowers","year":"2024","journal-title":"Cureus"},{"key":"B10","doi-asserted-by":"publisher","first-page":"406","DOI":"10.7861\/clinmedicine.18-5-406","article-title":"Spontaneous splenic rupture secondary to dabigatran: the last in a series of unfortunate events","volume":"18","author":"Carey","year":"2018","journal-title":"Clin. Med. (Lond)."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1016\/S0140-6736(20)32439-9","article-title":"Direct oral anticoagulants: evidence and unresolved issues","volume":"396","author":"Chan","year":"2020","journal-title":"Lancet"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1056\/NEJMoa0905561","article-title":"Dabigatran versus warfarin in patients with atrial fibrillation","volume":"361","author":"Connolly","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1056\/NEJMoa1310907","article-title":"Edoxaban versus warfarin in patients with atrial fibrillation","volume":"369","author":"Giugliano","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"950.e953","DOI":"10.1016\/j.ajem.2014.01.049","article-title":"Spontaneus splenic rupture in a patient treated with rivaroxaban","volume":"32","author":"Gonzva","year":"2014","journal-title":"Am. J. Emerg. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1056\/NEJMoa1107039","article-title":"Apixaban versus warfarin in patients with atrial fibrillation","volume":"365","author":"Granger","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"B16","article-title":"Acute management of Rivaroxaban-Induced splenic rupture: a case report","author":"Hetzler","year":"2021"},{"key":"B17","doi-asserted-by":"publisher","first-page":"155","DOI":"10.5811\/cpcem.1399","article-title":"Transcatheter arterial embolization for atraumatic splenic rupture in TEE-negative endocarditis: a case report","volume":"8","author":"High","year":"2024","journal-title":"Clin. Pract. Cases Emerg. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1080\/17425255.2023.2287472","article-title":"Pharmacokinetics and pharmacodynamics of direct oral anticoagulants","volume":"19","author":"Hindley","year":"2023","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1044.e1041","DOI":"10.1016\/j.ajem.2019.12.006","article-title":"Spontaneous splenic hemorrhage in a patient on apixiban","volume":"38","author":"Janke","year":"2020","journal-title":"Am. J. Emerg. Med."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2017-221288","article-title":"Splenic rupture following synchronised direct current cardioversion","volume":"2017","author":"Kaufman","year":"2017","journal-title":"BMJ Case Rep."},{"key":"B22","doi-asserted-by":"publisher","first-page":"107708","DOI":"10.1016\/j.ijscr.2022.107708","article-title":"Refractory splenic bleeding from splenic angiosarcoma: a case report and literature review","volume":"99","author":"Kawazoe","year":"2022","journal-title":"Int. J. Surg. Case Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e6462","DOI":"10.1002\/ccr3.6462","article-title":"Atraumatic splenic rupture in a patient treated with rivaroxaban: a case report and a narrative review","volume":"10","author":"Labaki","year":"2022","journal-title":"Clin. Case Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"5827694","DOI":"10.1155\/2019\/5827694","article-title":"Diagnosis and treatment of atraumatic splenic rupture: experience of 8 cases","volume":"2019","author":"Liu","year":"2019","journal-title":"Gastroenterol. Res. Pract."},{"key":"B25","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1111\/acem.14763","article-title":"Direct oral anticoagulants versus conventional anticoagulants for deep vein thrombosis","volume":"30","author":"Long","year":"2023","journal-title":"Acad. Emerg. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.ciresp.2019.06.015","article-title":"Spontaneous splenic rupture associated with apixaban","volume":"98","author":"Lopez Marcano","year":"2020","journal-title":"Cir. Esp. (Engl Ed)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1186\/s13256-016-1012-6","article-title":"Spontaneous splenic rupture associated with apixaban: a case report","volume":"10","author":"Lowry","year":"2016","journal-title":"J. Med. Case Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2082","DOI":"10.1016\/j.ajem.2011.10.031","article-title":"Spontaneous splenic hemorrhage after initiation of dabigatran (Pradaxa) for atrial fibrillation","volume":"30","author":"Moore","year":"2012","journal-title":"Am. J. Emerg. Med."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2017-221692","article-title":"Chronic lymphocytic leukaemia and spontaneous rupture of spleen","volume":"2018","author":"Mourato Nunes","year":"2018","journal-title":"BMJ Case Rep."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2017-223237","article-title":"Spontaneous splenic rupture due to rivaroxaban","volume":"2018","author":"Nagaraja","year":"2018","journal-title":"BMJ Case Rep."},{"key":"B31","doi-asserted-by":"publisher","first-page":"134","DOI":"10.5455\/ijsm.20150917100638","article-title":"Spontaneous splenic rupture secondary to rivaroxaban: rare but raising","volume":"2","author":"Naseem","year":"2015","journal-title":"Int. J. Surg. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/232470962110264","article-title":"Atraumatic splenic rupture in a patienton apixaban and dual antiplatelet therapy","volume":"9","author":"Natarajan","year":"2021","journal-title":"J. Investigative Med. High Impact Case Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e38992","DOI":"10.7759\/cureus.38992","article-title":"Atraumatic splenic rupture: a notable complication of rivaroxaban use","volume":"15","author":"Ostos Perez","year":"2023","journal-title":"Cureus"},{"key":"B34","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1056\/NEJMoa1009638","article-title":"Rivaroxaban versus warfarin in nonvalvular atrial fibrillation","volume":"365","author":"Patel","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1681\/asn.20213210s1799e","article-title":"Atraumatic splenic rupture in a patient on apixaban and clopidogrel","volume":"32","author":"Patnaik","year":"2021","journal-title":"J. Am. Soc. Nephrol."},{"key":"B36","first-page":"36","article-title":"Spontaneous splenic rupture under Xarelto","author":"Pietsch","year":"2021","journal-title":"EC Gastroenterology Dig. Syst."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1002\/bjs.6737","article-title":"Systematic review of atraumatic splenic rupture","volume":"96","author":"Renzulli","year":"2009","journal-title":"Br. J. Surg."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.61409\/V05230328","article-title":"Atraumatic splenic rupture","volume":"186","author":"Soeborg","year":"2024","journal-title":"Atraumatic Splenic Rupture"},{"key":"B39","doi-asserted-by":"publisher","first-page":"105641","DOI":"10.1016\/j.ijscr.2021.02.027","article-title":"Peliosis lienalis with atraumatic splenic rupture in a patient with chronic myelomonocytic leukemia: a case report","volume":"80","author":"Widmer","year":"2021","journal-title":"Int. J. Surg. Case Rep."},{"key":"B40","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.jacc.2023.08.017","article-title":"2023 ACC\/AHA\/ACCP\/HRS guideline for the diagnosis and management of atrial fibrillation: a report of the American college of cardiology\/American heart association joint committee on clinical practice guidelines","volume":"83","author":"Writing Committee","year":"2024","journal-title":"J. Am. Coll. Cardiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.ijscr.2020.04.050","article-title":"Atraumatic splenic rupture in a patient treated with apixaban: a case report","volume":"71","author":"Yau","year":"2020","journal-title":"Int. J. Surg. Case Rep."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1777780\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:30:54Z","timestamp":1772775054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1777780\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,6]]},"references-count":41,"alternative-id":["10.3389\/fphar.2026.1777780"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1777780","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,6]]},"article-number":"1777780"}}