{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:35:48Z","timestamp":1792056948682,"version":"4.4.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Thrombocytopenia has been described in most patients with acute and chronic liver failure. Decreased platelet production and decreased half\u2010life of platelets might be a consequence of low levels of thrombopoietin (TPO) in these patients. Platelet production is tightly regulated to avoid bleeding complications after vessel injury and can be enhanced under elevated platelet destruction as observed in liver disease. Thrombopoietin (TPO) is the primary regulator of platelet biogenesis and supports proliferation and differentiation of megakaryocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Recent work provided evidence for the control of TPO mRNA expression in liver and bone marrow (BM) by scanning circulating platelets. The Ashwell\u2010Morell receptor (AMR) was identified to bind desialylated platelets to regulate hepatic thrombopoietin (TPO) production by Janus kinase (JAK2)\/signal transducer and activator of transcription (STAT3) activation.\u00a0Two\u2010thirds partial hepatectomy (PHx) was performed in mice. Platelet activation and clearance by AMR\/JAK2\/STAT3 signaling and TPO production were analyzed at different time points after PHx. Here, we demonstrate that PHx in mice led to thrombocytopenia and platelet activation defects leading to bleeding complications, but unaltered arterial thrombosis, in these mice. Platelet counts were rapidly restored by up\u2010regulation and crosstalk of the AMR and the IL\u20106 receptor (IL\u20106R) to induce JAK2\u2010STAT3\u2010TPO activation in the liver, accompanied by an increased number of megakaryocytes in spleen and BM before liver was completely regenerated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The AMR\/IL\u20106R\u2010STAT3\u2010TPO signaling pathway is an acute\u2010phase response to liver injury to reconstitute hemostasis. Bleeding complications were attributable to thrombocytopenia and platelet defects induced by elevated PGI<jats:sub>2<\/jats:sub>, NO, and bile acid plasma levels early after PHx that might also be causative for the high mortality in patients with liver disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31698","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T16:37:04Z","timestamp":1609173424000},"page":"411-427","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":28,"title":["Efficiently Restored Thrombopoietin Production by Ashwell\u2010Morell Receptor and IL\u20106R Induced Janus Kinase 2\/Signal Transducer and Activator of Transcription Signaling Early After Partial Hepatectomy"],"prefix":"10.1097","volume":"74","author":[{"given":"Friedrich","family":"Reusswig","sequence":"first","affiliation":[{"name":"Clinic of Vascular and Endovascular Surgery,Medical Faculty and University Hospital,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nastaran","family":"Fazel Modares","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology II, Medical Faculty,Heinrich\u2010Heine University,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Brechtenkamp","sequence":"additional","affiliation":[{"name":"Clinic of Vascular and Endovascular Surgery,Medical Faculty and University Hospital,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Wienands","sequence":"additional","affiliation":[{"name":"Clinic of Vascular and Endovascular Surgery,Medical Faculty and University Hospital,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Clinic of Vascular and Endovascular Surgery,Medical Faculty and University Hospital,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Behnke","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology II, Medical Faculty,Heinrich\u2010Heine University,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa M.","family":"Lee\u2010Sundlov","sequence":"additional","affiliation":[{"name":"Blood Research Institute Versiti,Milwaukee,WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diran","family":"Herebian","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology and Pediatric Cardiology,Medical Faculty,Heinrich\u2010Heine\u2010University,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Scheller","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and 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