{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T01:19:04Z","timestamp":1772068744447,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,4,28]],"date-time":"2018-04-28T00:00:00Z","timestamp":1524873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Protein C (PrC), a physiological anticoagulant, regulates inflammation and cell death and has known predictive\/therapeutic roles in sepsis. Accumulating evidences suggest plasma hypercoagulability results in progression of fibrosis and formation of microclots causing end\u2010organ dysfunction. We investigated a possible association between natural anticoagulants\u2014PrC, protein S (PrS) and antithrombin <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content>)\u2014and clinical outcomes in cirrhotics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Functional PrC, PrS and <jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content> were analysed in 515 cirrhotic patients and compared with 229 noncirrhotics. Among those with cirrhosis, we conducted multivariable predictive model on 3\u2010month survival to assess the prognostic ability of anticoagulants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Protein C (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), PrS (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) and <jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content> (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) levels were lower in cirrhotics compared with noncirrhotics. In addition, patients with Child\u2010Pugh (<jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>)\u2010C had significantly lower (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05) functional PrC, PrS and <jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content> levels than <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>\u2010B, <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>\u2010A and noncirrhotic patients. Low PrC function correlated with markers of liver dysfunction and inflammation: <jats:styled-content style=\"fixed-case\">INR<\/jats:styled-content>(<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u2212.72, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), bilirubin (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u2212.620, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), albumin (<jats:italic>r<\/jats:italic>\u00a0=\u00a0.539, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), creatinine (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u2212.417, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001), ferritin (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u2212.68, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.035), procalcitonin (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u2212.79, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.01), raised <jats:styled-content style=\"fixed-case\">ESR<\/jats:styled-content> (<jats:italic>r<\/jats:italic>\u00a0=\u00a0.56, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001) and liver fibrosis (<jats:italic>r<\/jats:italic>\u00a0=\u00a0\u2212.840, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001). Patients who died (n\u00a0=\u00a0160) had significantly lower median PrC function (23.8%, 16.3\u201033.0]) compared with those who remained alive (74.9%, [59.7\u201092.5]); <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001. In a multivariable predictive model using PrC, and <jats:styled-content style=\"fixed-case\">MELD<\/jats:styled-content> score, we found a significant impact of low PrC levels on survival (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001, <jats:styled-content style=\"fixed-case\">IRR<\/jats:styled-content>\u00a0=\u00a00.97, 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\u00a0=\u00a00.96\u20100.98). Receiver operating characteristic (<jats:styled-content style=\"fixed-case\">ROC<\/jats:styled-content>) curve analysis revealed that functional PrC levels &lt;52% were associated with increased mortality (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Low functional protein C level correlated with markers of liver dysfunction, inflammation and sepsis and independently predicted mortality at 3\u00a0months in cirrhotics, especially if functional levels were &lt;52%.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijlh.12836","type":"journal-article","created":{"date-parts":[[2018,4,28]],"date-time":"2018-04-28T15:20:51Z","timestamp":1524928851000},"page":"466-472","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Decreased protein C function predicts mortality in patients with cirrhosis"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9611-1869","authenticated-orcid":false,"given":"A. G.","family":"Patil","sequence":"first","affiliation":[{"name":"Department of Clinical Haematology Institute of Liver &amp; Biliary Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Bihari","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology Institute of Liver &amp; Biliary Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. D.","family":"Shewade","sequence":"additional","affiliation":[{"name":"South\u2010East Asia Office International Union Against Tuberculosis and Lung Disease (The Union)  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Nigam","sequence":"additional","affiliation":[{"name":"Department of Clinical Haematology Institute of Liver &amp; Biliary Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. K.","family":"Sarin","sequence":"additional","affiliation":[{"name":"Department of Hepatology Institute of Liver &amp; Biliary Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2013.02.026"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.07.018"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.03.036"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.124.3_suppl.26S"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01573.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2016.04.012"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19960530)15:10<969::AID-SIM211>3.0.CO;2-9"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v12.i48.7725"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.03.013"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000216879"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-8329(97)00082-7"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.4103\/0377-4929.188119"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.08.045"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0012.2007.00728.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/13651820701599033"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200005150-00023"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1076029612440034"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23653"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/1076029615587356"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.03015.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.8.1206"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2009.03.011"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-1203"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21920"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.04.017"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2003.10.016"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mbc.0000174080.54871.6b"}],"container-title":["International Journal of Laboratory Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fijlh.12836","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ijlh.12836","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T01:20:26Z","timestamp":1695000026000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ijlh.12836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,28]]},"references-count":27,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,8]]}},"alternative-id":["10.1111\/ijlh.12836"],"URL":"https:\/\/doi.org\/10.1111\/ijlh.12836","archive":["Portico"],"relation":{},"ISSN":["1751-5521","1751-553X"],"issn-type":[{"value":"1751-5521","type":"print"},{"value":"1751-553X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,28]]},"assertion":[{"value":"2017-11-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}