{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:45:00Z","timestamp":1791773100221,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,7,10]],"date-time":"2021-07-10T00:00:00Z","timestamp":1625875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>While direct oral anticoagulants (DOACs) are increasingly used in patients with liver disease, safety data especially in advanced chronic liver disease (ACLD) are limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Liver disease patients receiving DOAC treatment (ACLD: n\u00a0=\u00a0104; vascular liver disease: n\u00a0=\u00a029) or vitamin K antagonists (VKA)\/low\u2010molecular\u2010weight heparin (LMWH; ACLD: n\u00a0=\u00a045; vascular: n\u00a0=\u00a013) between January 2010 and September 2020 were retrospectively included. Invasive procedures and bleeding events were recorded. Calibrated anti\u2010Xa peak levels and thrombomodulin\u2010modified thrombin generation assays (TM\u2010TGAs) were measured in a subgroup of 35\/28 DOAC patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among patients receiving DOAC, 55 (41.3%) had advanced liver dysfunction (Child\u2010Pugh\u2010stage [CPS] B\/C) and 66 (49.6%) had experienced decompensation. Overall, 205 procedures were performed in 60 patients and procedure\u2010related bleedings occurred in 7 (11.7%) patients. Additionally, 38 (28.6%) patients experienced spontaneous (15 minor, 23 major) bleedings during a median follow\u2010up of 10.5 (IQR: 4.0\u201027.8) months. Spontaneous bleedings in ACLD patients were more common in CPS\u2010B\/C (at 12\u00a0months: 36.9% vs CPS\u2010A: 15.9%, subdistribution hazard ratio [SHR]: 3.23 [95% CI: 1.59\u20106.58], <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), as were major bleedings (at 12\u00a0months: 22.0% vs 5.0%, SHR: 5.82 [95% CI: 2.00\u201016.90], <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001). Importantly, CPS (adjusted SHR: 4.12 [91% CI: 1.82\u20109.37], <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), but not the presence of hepatocellular carcinoma or varices, was independently associated with major bleeding during DOAC treatment. Additionally, ACLD patients experiencing bleeding had worse overall survival (at 12\u00a0months: 88.9% vs 95.0% without bleeding; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001). Edoxaban anti\u2010Xa peak levels were higher in patients with CPS\u2010B\/C (345 [95% CI: 169\u2010395] vs CPS\u2010A: 137 [95% CI: 96\u2010248] ng\/mL, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.048) and were associated with lower TM\u2010TGA. Importantly, spontaneous bleeding rates were comparable to VKA\/LMWH patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Anticoagulants including DOACs should be used with caution in patients with advanced liver disease due to a significant rate of spontaneous bleeding events.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14992","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T15:12:55Z","timestamp":1624288375000},"page":"2159-2170","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Safety of direct oral anticoagulants in patients with advanced liver disease"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0411-166X","authenticated-orcid":false,"given":"Georg","family":"Semmler","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine III Medical University of Vienna Vienna Austria"},{"name":"Vienna Hepatic Hemodynamic Lab Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2807-3565","authenticated-orcid":false,"given":"Katharina","family":"Pomej","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine III Medical University of Vienna Vienna Austria"},{"name":"Vienna Hepatic Hemodynamic Lab Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9363-8518","authenticated-orcid":false,"given":"David J. 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