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This study defines evolution of coagulopathy in 10 pigs with acetaminophen (APAP)-induced ALI compared to 3 Controls. APAP administration began at 0\u2009h and continued to \u2018ALF\u2019, defined as INR &gt;3. In APAP pigs, INR was 1.05\u2009\u00b1\u20090.02 at 0\u2009h, 2.15\u2009\u00b1\u20090.43 at 16\u2009h and\u2009&gt;\u20093 at 18\u2009\u00b1\u20091\u2009h. At 12\u2009h thromboelastography (TEG) demonstrated increased clot formation rate, associated with portal vein platelet aggregates and reductions in protein C, protein S, antithrombin and A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats\u201313 (ADAMTS-13) to 60%, 24%, 47% and 32% normal respectively. At 18\u2009\u00b1\u20091\u2009h, INR\u2009&gt;\u20093 was associated with: hypocoagulable TEG profile with heparin-like effect; falls in thrombin generation, Factor V and Factor VIII to 52%, 19% and 17% normal respectively; further decline in anticoagulants; thrombocytopenia; neutrophilia and endotoxemia. Multivariate analysis, found that ADAMTS-13 was an independent predictor of a hypercoagulable TEG profile and platelet count, endotoxin, Protein C and fibrinogen were independent predictors of a hypocoagulable TEG profile. INR remained normal in Controls. Dynamic changes in coagulation occur with progression of ALI: a pro-thrombotic state progresses to hypocoagulability.<\/jats:p>","DOI":"10.1038\/s41598-017-09508-3","type":"journal-article","created":{"date-parts":[[2017,8,18]],"date-time":"2017-08-18T13:29:24Z","timestamp":1503062964000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Hypercoagulability progresses to hypocoagulability during evolution of acetaminophen-induced acute liver injury in pigs"],"prefix":"10.1038","volume":"7","author":[{"given":"Karla Chui Luan","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Baker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Mallett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Riddell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pratima","family":"Chowdary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hatim","family":"Alibhai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Mei","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Priestnall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo","family":"Stanzani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Davies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajeshwar","family":"Mookerjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajiv","family":"Jalan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Banwari","family":"Agarwal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,8,24]]},"reference":[{"key":"9508_CR1","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/0016-5085(89)90081-4","volume":"97","author":"JG O\u2019Grady","year":"1989","unstructured":"O\u2019Grady, J. 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Rajiv Jalan has research collaborations with Ocera, Grifols, Norgine and Gambro, consults for Ocera and Conatus and has received speaking fees from Norgine and Grifols. Rajiv Jalan and Nathan Davies are inventors of University College London-Liver Dialysis Device, which has been patented by UCL and licensed to Yaqrit Limited.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"9347"}}