{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T22:04:22Z","timestamp":1780437862689,"version":"3.54.1"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T00:00:00Z","timestamp":1559174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T00:00:00Z","timestamp":1559174400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver Transpl"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:p>Everolimus (EVR) is a mammalian target of rapamycin (mTOR) inhibitor commonly used for immunosuppression (IS) after liver transplantation (LT). However, there are concerns about whether mTOR inhibitors may move the hemostatic balance toward a higher likelihood of thrombosis. The present study aimed to investigate potential coagulation disorders after the administration of EVR. We evaluated 54 patients after conversion to an EVR\u2010based IS regimen (n\u00a0=\u00a026) and compared those patients with patients who were switched to extended\u2010release tacrolimus (TAC) but had never received EVR (n\u00a0=\u00a028). At baseline and again at 1 month and 6 months after conversion, we measured international normalized ratio, activated partial thromboplastin time, and anticoagulation and fibrinolysis factors, and we performed rotational thromboelastometry (ROTEM). Data were analyzed with a Mann\u2010Whitney U test, a repeated\u2010measure analysis of variance, and a Fisher\u2019s exact test. Statistical significance was set at the level of <jats:italic toggle=\"yes\">P<\/jats:italic> \u2264 0.05. Plasma levels of von Willebrand factor, fibrinogen, and factor VIII were significantly higher than baseline levels at 1 month and 6 months after conversion of IS to EVR (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.001); plasma levels of protein C, protein S, and plasminogen also increased significantly (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.001). ROTEM confirmed a significant increase in maximum clot firmness in EXTEM, INTEM, and FIBTEM assays (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.001). In all assays, maximum lysis was significantly lower than baseline levels at 1 month and 6 months after conversion to EVR. Patients converted to IS with extended\u2010release TAC exhibited no significant changes in coagulation variables. Retrospective analysis showed a significantly higher incidence of thromboembolic complications among patients treated with EVR\u2010based IS than among those treated with extended\u2010release TAC (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.01). In conclusion, the administration of EVR after LT seems to modify hemostasis to a procoagulant state. Thrombophilia screening before conversion may determine which patients will benefit from conversion to EVR\u2010based IS.<\/jats:p>","DOI":"10.1002\/lt.25476","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T15:50:17Z","timestamp":1556207417000},"page":"1054-1065","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Effect of Immunosuppression on Coagulation After Liver Transplantation"],"prefix":"10.1097","volume":"25","author":[{"given":"Sotiria","family":"Bedreli","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology,University Hospital Essen, University of Duisburg\u2010Essen,Essen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Straub","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,University Hospital Essen, University of Duisburg\u2010Essen,Essen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Achterfeld","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,University Hospital Essen, University of Duisburg\u2010Essen,Essen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Willuweit","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,University Hospital Essen, University of Duisburg\u2010Essen,Essen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonios","family":"Katsounas","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases,University of Magdeburg,Magdeburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuat","family":"Saner","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery,University Hospital Essen, University of Duisburg\u2010Essen,Essen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiner","family":"Wedemeyer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,University Hospital Essen, University of Duisburg\u2010Essen,Essen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Herzer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,University Hospital Essen, University of Duisburg\u2010Essen,Essen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,5,30]]},"reference":[{"key":"lt25476-bib-0001-20240115","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1111\/j.1600-6143.2012.04212.x","article-title":"Everolimus with reduced tacrolimus improves renal function in de novo liver transplant recipients: a 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to prednisolone\/everolimus as an alternative weaning regimen associates with beneficial renal transplant histology and function: the randomized\u2010controlled MECANO trial","volume":"17","year":"2017","journal-title":"Am J Transplant"},{"key":"lt25476-bib-0017-20240115","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/ajt.12543","article-title":"De novo sirolimus and reduced\u2010dose tacrolimus versus standard\u2010dose tacrolimus after liver transplantation: the 2000\u20102003 phase II prospective randomized trial","volume":"14","year":"2014","journal-title":"Am J Transplant"},{"key":"lt25476-bib-0018-20240115","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1111\/ctr.12744","article-title":"Long\u2010term follow\u2010up of five yr shows superior renal function with everolimus plus early calcineurin inhibitor withdrawal in the PROTECT randomized liver transplantation study","volume":"30","year":"2016","journal-title":"Clin 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