{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:55:30Z","timestamp":1780102530636,"version":"3.54.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Data on factor XIII (FXIII) activity in patients on extracorporeal membrane oxygenation (ECMO) are scarce. In this prospective, observational, single-centre study, we determined the rate of acquired FXIII deficiency in 44 adults during ECMO. We evaluated the relationship between minimum FXIII activity, haemoglobin levels, transfusion requirements, as well as the occurrence of major bleeding events. Descriptive statistical methods, bivariate correlation and receiver operating characteristic curve analyses were applied. Acquired FXIII deficiency (FXIII activity\u2009&lt;\u200970%) was found in 41\/44 patients [93.2% (95% CI 85.7\u2013100%)] during ECMO. The minimum FXIII activity was correlated with minimum haemoglobin levels (Spearman-\n                    <jats:italic>rho<\/jats:italic>\n                    , 0.331, 95% CI 0.02\u20130.57,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03), packed red blood cell transfusion requirements (Spearman-\n                    <jats:italic>rho<\/jats:italic>\n                    , \u2212 0.32, 95% CI \u2212\u20090.58 to 0.00,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03), but not the occurrence of major bleeding events (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.32, Hodges-Lehmann difference \u2212 4.0%, 95% CI \u2212\u200915.0 to 5.0%) during ECMO. The area under the receiver operating characteristic curve for minimum FXIII activity to predict the occurrence of major bleeding events during ECMO was 0.602 (95% CI 0.375\u20130.828). The lowest FXIII activity to predict a major bleeding event was 51.0% and 55.5% (Youden index for both, 0.27), respectively. In conclusion, acquired FXIII deficiency is highly frequent in adult ECMO patients. Lower FXIII activity showed modest correlations with nadir haemoglobin and pRBC exposure, but did not discriminate patients with major bleeding. Larger studies are needed to determine whether routine FXIII monitoring and targeted replacement improve outcomes during ECMO.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-26452-9","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T12:20:00Z","timestamp":1762518000000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Acquired factor XIII deficiency in adult patients during ECMO: a prospective observational study"],"prefix":"10.1038","volume":"15","author":[{"given":"Matthias","family":"Noitz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Jenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Tschoellitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxane","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romana","family":"Erblich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Krenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Tomi\u0107-Mahe\u010di\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin W.","family":"D\u00fcnser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Zierer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Meier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"26452_CR1","doi-asserted-by":"publisher","first-page":"1965","DOI":"10.1056\/NEJMoa1800385","volume":"378","author":"A Combes","year":"2018","unstructured":"Combes, A. et al. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N. Engl. J. Med. 378, 1965\u20131975 (2018).","journal-title":"N. Engl. J. Med."},{"key":"26452_CR2","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/S0140-6736(20)31047-3","volume":"396","author":"A Combes","year":"2020","unstructured":"Combes, A., Price, S., Slutsky, A. S. & Brodie, D. Temporary circulatory support for cardiogenic shock. Lancet 396, 199\u2013212 (2020).","journal-title":"Lancet"},{"key":"26452_CR3","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.athoracsur.2015.07.046","volume":"101","author":"M Mazzeffi","year":"2016","unstructured":"Mazzeffi, M. et al. Bleeding, transfusion, and mortality on extracorporeal life support: ECLS working group on thrombosis and hemostasis. Ann. Thorac. Surg. 101, 682\u2013689 (2016).","journal-title":"Ann. Thorac. Surg."},{"key":"26452_CR4","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/s00134-021-06593-x","volume":"48","author":"JI Nunez","year":"2022","unstructured":"Nunez, J. I. et al. Bleeding and thrombotic events in adults supported with venovenous extracorporeal membrane oxygenation: an ELSO registry analysis. Intensive Care. Med. 48, 213\u2013224 (2022).","journal-title":"Intensive Care. Med."},{"key":"26452_CR5","doi-asserted-by":"publisher","first-page":"3496","DOI":"10.3390\/diagnostics13233496","volume":"13","author":"F Frantzeskaki","year":"2023","unstructured":"Frantzeskaki, F. et al. Extracorporeal membrane oxygenation (ECMO)-associated coagulopathy in adults. Diagnostics 13, 3496 (2023).","journal-title":"Diagnostics"},{"key":"26452_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bvth.2025.100064","volume":"2","author":"H Jerrold","year":"2025","unstructured":"Jerrold, H. et al. ECMO-induced coagulopathy: strategic initiatives for research and clinical practice (a workshop report of the NHLBI). Blood Vessels, Thrombosis & Hemostasis 2, 100064 (2025).","journal-title":"Blood Vessels, Thrombosis & Hemostasis"},{"key":"26452_CR7","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1007\/s00134-016-4312-9","volume":"42","author":"D Abrams","year":"2016","unstructured":"Abrams, D. et al. Thrombocytopenia and extracorporeal membrane oxygenation in adults with acute respiratory failure: A cohort study. Intensive Care. Med. 42, 844\u2013852 (2016).","journal-title":"Intensive Care. Med."},{"key":"26452_CR8","doi-asserted-by":"publisher","first-page":"e400","DOI":"10.1097\/CCM.0000000000004286","volume":"48","author":"T Granja","year":"2020","unstructured":"Granja, T. et al. Multi-modal characterization of the coagulopathy associated with extracorporeal membrane oxygenation. Crit. Care Med. 48, e400\u2013e408 (2020).","journal-title":"Crit. Care Med."},{"key":"26452_CR9","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1016\/j.healun.2018.03.013","volume":"372","author":"J Kalbhenn","year":"2018","unstructured":"Kalbhenn, J., Schlagenhauf, A., Rosenfelder, S., Schmutz, A. & Zieger, B. Acquired von Willebrand syndrome and impaired platelet function during venovenous extracorporeal membrane oxygenation: Rapid onset and fast recovery. J. Heart Lung Transpl. 372, 985\u2013991 (2018).","journal-title":"J. Heart Lung Transpl."},{"key":"26452_CR10","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1111\/jth.12455","volume":"12","author":"EL Hethershaw","year":"2014","unstructured":"Hethershaw, E. L. et al. The effect of blood coagulation factor XIII on fibrin clot structure and fibrinolysis. J. Thromb. Haemost. 12, 197\u2013205 (2014).","journal-title":"J. Thromb. Haemost."},{"key":"26452_CR11","first-page":"70","volume":"23","author":"TT Mahe\u010di\u0107","year":"2025","unstructured":"Mahe\u010di\u0107, T. T., Konosi\u0107, S., Noitz, M. & Bobinac, M. Coagulation factor XIII - last to think about?. Blood Transfus. 23, 70\u201374 (2025).","journal-title":"Blood Transfus."},{"key":"26452_CR12","doi-asserted-by":"publisher","first-page":"3894","DOI":"10.1007\/s10620-024-08651-y","volume":"69","author":"A Traninger","year":"2024","unstructured":"Traninger, A. et al. Acquired low factor XIII activity is associated with an increased need for blood transfusions in patients with gastrointestinal bleedings. Dig. Dis. Sci. 69, 3894\u20133900 (2024).","journal-title":"Dig. Dis. Sci."},{"key":"26452_CR13","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s13054-022-03940-2","volume":"26","author":"C Kleber","year":"2022","unstructured":"Kleber, C. et al. The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing. Crit. Care 26, 69 (2022).","journal-title":"Crit. Care"},{"key":"26452_CR14","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.jcrc.2019.11.012","volume":"56","author":"EH Adam","year":"2020","unstructured":"Adam, E. H. et al. Factor XIII activity in patients requiring surgical re-exploration for bleeding after elective cardiac surgery - a prospective case control study. J. Crit. Care 56, 18\u201325 (2020).","journal-title":"J. Crit. Care"},{"key":"26452_CR15","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1177\/0267659115579714","volume":"30","author":"J Kalbhenn","year":"2015","unstructured":"Kalbhenn, J., Wittau, N., Schmutz, A., Zieger, B. & Schmidt, R. Identification of acquired coagulation disorders and effects of target-controlled coagulation factor substitution on the incidence and severity of spontaneous intracranial bleeding during veno-venous ECMO therapy. Perfusion 30, 675\u2013682 (2015).","journal-title":"Perfusion"},{"key":"26452_CR16","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s10047-019-01148-w","volume":"23","author":"A Ito","year":"2020","unstructured":"Ito, A. et al. Acquired factor XIII deficiency in two patients with bleeding events during veno-venous extracorporeal membrane oxygenation treatment. J. Artif. Organs 23, 283\u2013287 (2020).","journal-title":"J. Artif. Organs"},{"key":"26452_CR17","doi-asserted-by":"publisher","first-page":"4774","DOI":"10.1182\/blood.V122.21.4774.4774","volume":"122","author":"D Sanchez","year":"2013","unstructured":"Sanchez, D. et al. A pilot study to examine the effect of extracorporeal membrane oxygenation (ECMO) on plasma factor XIII levels. Blood 122, 4774 (2013).","journal-title":"Blood"},{"key":"26452_CR18","doi-asserted-by":"publisher","first-page":"4115","DOI":"10.3390\/jcm12124115","volume":"12","author":"M Noitz","year":"2023","unstructured":"Noitz, M. et al. Acquired factor XIII deficiency is common during ECMO therapy and associated with major bleeding events and transfusion requirements. J. Clin. Med. 12, 4115 (2023).","journal-title":"J. Clin. Med."},{"key":"26452_CR19","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","volume":"61","author":"E Von Elm","year":"2008","unstructured":"Von Elm, E. et al. STROBE initiative the strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. J. Clin. Epidemiol. 61, 344\u2013349 (2008).","journal-title":"J. Clin. Epidemiol."},{"key":"26452_CR20","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1097\/MAT.0000000000001652","volume":"68","author":"ABV McMichael","year":"2022","unstructured":"McMichael, A. B. V. et al. 2021 ELSO adult and pediatric anticoagulation guidelines. ASAIO J. 68, 303\u2013310 (2022).","journal-title":"ASAIO J."},{"key":"26452_CR21","doi-asserted-by":"publisher","DOI":"10.1097\/EA9.0000000000000035","volume":"2","author":"O Duranteau","year":"2023","unstructured":"Duranteau, O., Tatar, G., Demulder, A. & Tuna, T. Acquired factor XIII deficiency: A scoping review. Eur. J. Anaesthesiol. Intensive Care. 2, e0035 (2023).","journal-title":"Eur. J. Anaesthesiol. Intensive Care."},{"key":"26452_CR22","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1111\/hae.12474","volume":"20","author":"T de Jager","year":"2014","unstructured":"de Jager, T., Pericleous, L., Kokot-Kierepa, M., Naderi, M. & Karimi, M. The burden and management of FXIII deficiency. Haemophilia 20, 733\u2013740 (2014).","journal-title":"Haemophilia"},{"key":"26452_CR23","unstructured":"Laurance Lequier, G.A. et al. ELSO Anticoagulation Guideline. Extracorporeal Life Support Organization, editor. Extracorporeal Life Support Organization (ELSO); Ann Arbor, MI, USA https:\/\/www.elso.org\/portals\/0\/files\/elsoanticoagulationguideline8-2014-table-contents.pdf.\u00a0(2014)."},{"key":"26452_CR24","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.3390\/ijms22063055","volume":"22","author":"FSM Alshehri","year":"2021","unstructured":"Alshehri, F. S. M., Whyte, C. S. & Mutch, N. J. Factor XIII-A: an indispensable \u201cFactor\u201d in haemostasis and wound healing. Int. J. Mol. Sci. 22, 3055 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"26452_CR25","doi-asserted-by":"publisher","first-page":"S77","DOI":"10.1016\/j.thromres.2012.02.040","volume":"129","author":"Z Bagoly","year":"2012","unstructured":"Bagoly, Z., Katona, E. & Muszbek, L. Factor XIII and inflammatory cells. Thromb. Res. 129, S77\u2013S81 (2012).","journal-title":"Thromb. Res."},{"key":"26452_CR26","doi-asserted-by":"publisher","first-page":"278","DOI":"10.5858\/arpa.2012-0639-RS","volume":"138","author":"A Tahlan","year":"2014","unstructured":"Tahlan, A. & Ahluwalia, J. Factor XIII: congenital deficiency factor XIII, acquired deficiency, factor XIII A-subunit, and factor XIII B-subunit. Arch. Pathol. Lab. Med. 138, 278\u2013281 (2014).","journal-title":"Arch. Pathol. Lab. Med."},{"key":"26452_CR27","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.3390\/jcm10061203","volume":"10","author":"O Moerer","year":"2021","unstructured":"Moerer, O., Huber-Petersen, J. F., Schaeper, J., Binder, C. & Wand, S. Factor XIII activity might already be impaired before veno-venous ECMO in ARDS patients: a prospective, observational single-center cohort study. J. Clin. Med. 10, 1203 (2021).","journal-title":"J. Clin. Med."},{"key":"26452_CR28","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1111\/j.1538-7836.2012.04653.x","volume":"10","author":"F Peyvandi","year":"2012","unstructured":"Peyvandi, F. et al. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J. Thromb. Haemost. 10, 615\u2013621 (2012).","journal-title":"J. Thromb. Haemost."},{"key":"26452_CR29","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1160\/TH14-07-0625","volume":"113","author":"G Dickneite","year":"2015","unstructured":"Dickneite, G. et al. Coagulation factor XIII: a multifunctional transglutaminase with clinical potential in a range of conditions. Thromb. Haemost. 113, 686\u2013697 (2015).","journal-title":"Thromb. Haemost."},{"key":"26452_CR30","doi-asserted-by":"publisher","first-page":"156","DOI":"10.23736\/S0375-9393.22.15772-X","volume":"88","author":"P Guilabert","year":"2022","unstructured":"Guilabert, P., Asmis, L., Cortina, V., Barret, J. P. & Colomina, M. J. Factor XIII and surgical bleeding. Minerva Anestesiol. 88, 156\u2013165 (2022).","journal-title":"Minerva Anestesiol."},{"key":"26452_CR31","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1097\/MBC.0000000000001326","volume":"35","author":"M \u017duni\u0107","year":"2024","unstructured":"\u017duni\u0107, M., Vre\u010da, N. & Bevc, S. The role of factor XIII in patient blood management. Blood Coagul. Fibrinolysis 35, 325\u2013333 (2024).","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"26452_CR32","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13049-017-0463-0","volume":"26","author":"A Kaserer","year":"2018","unstructured":"Kaserer, A. et al. Comparison of two different coagulation algorithms on the use of allogenic blood products and coagulation factors in severely injured trauma patients: a retrospective, multicentre, observational study. Scand. J. Trauma Resusc. Emerg. Med. 26, 4 (2018).","journal-title":"Scand. J. Trauma Resusc. Emerg. Med."},{"key":"26452_CR33","doi-asserted-by":"publisher","first-page":"e258","DOI":"10.1016\/S2352-3026(17)30077-7","volume":"4","author":"P Innerhofer","year":"2017","unstructured":"Innerhofer, P. et al. Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. Lancet Haematol. 4, e258\u2013e271 (2017).","journal-title":"Lancet Haematol."},{"key":"26452_CR34","doi-asserted-by":"publisher","first-page":"4174","DOI":"10.3390\/jcm11144174","volume":"11","author":"M Katzensteiner","year":"2022","unstructured":"Katzensteiner, M. et al. Factor XIII measurement and substitution in trauma patients after admission to an intensive care unit. J. Clin. Med. 11, 4174 (2022).","journal-title":"J. Clin. Med."},{"key":"26452_CR35","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1055\/s-2007-1010236","volume":"46","author":"O G\u00f6dje","year":"1998","unstructured":"G\u00f6dje, O., Haushofer, M., Lamm, P. & Reichart, B. The effect of factor XIII on bleeding in coronary surgery. Thorac. Cardiovasc. Surg. 46, 263\u2013267 (1998).","journal-title":"Thorac. Cardiovasc. Surg."},{"key":"26452_CR36","doi-asserted-by":"crossref","unstructured":"Rossaint, R. et al. The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition. Crit. Care 27, 80 (2023).","DOI":"10.1186\/s13054-023-04327-7"},{"key":"26452_CR37","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1097\/EJA.0000000000001803","volume":"40","author":"S Kietaibl","year":"2023","unstructured":"Kietaibl, S. et al. Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care: Second update 2022. Eur. J. Anaesthesiol. 40, 226\u2013304 (2023).","journal-title":"Eur. J. Anaesthesiol."},{"key":"26452_CR38","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1111\/jth.13893","volume":"16","author":"A Godier","year":"2018","unstructured":"Godier, A., Greinacher, A., Faraoni, D., Levy, J. H. & Samama, C. M. Use of factor concentrates for the management of perioperative bleeding: guidance from the SSC of the ISTH. J. Thromb. Haemost. 16, 170\u2013174 (2018).","journal-title":"J. Thromb. Haemost."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-26452-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-26452-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-26452-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T12:20:01Z","timestamp":1762518001000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-26452-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,7]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["26452"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-26452-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,7]]},"assertion":[{"value":"7 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 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":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"39110"}}