{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:10:23Z","timestamp":1778217023925,"version":"3.51.4"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Pediatric liver disease is frequently associated with abnormal conventional coagulation tests; however, prothrombin time expressed as international normalized ratio (PT-INR) incompletely reflect global hemostatic balance. Thrombin generation assay (TGA) provide an integrated assessment of coagulation and may offer complementary information in children with acute liver failure (ALF) and chronic liver disease (CLD). Methods: We enrolled 61 pediatric patients with liver disease (50 CLD, 8 ALF, 3 extrahepatic portal vein obstruction EHPVO) and 51 healthy controls. Platelet-poor plasma was prepared according to international recommendations. Thrombin generation was measured using ST Genesia (STG) with normalization to reference plasma. Group comparisons were performed using non-parametric tests; correlations between PT-INR and thrombin generation parameters were assessed, and principal component analysis (PCA) was used to explore the variance structure of thrombin generation indices and conventional coagulation variables. Results: PT-INR was significantly higher in patients than controls, particularly in ALF. Bleeding events were uncommon. Compared with controls, patients showed reduced levels of fibrinogen and multiple procoagulant\/anticoagulant factors (including antithrombin and protein C), with increased factor VIII. Among thrombin generation parameters, the endogenous thrombin potential (ETP) ratio differed significantly across groups (p = 0.001), while correlations between PT-INR and thrombin generation parameters were weak or absent, no significant associations were observed even at higher Pediatric\/Model for End-Stage Liver Disease scores. PCA separated thrombin generation indices from PT-INR and conventional coagulation factors, suggesting complementary information. Conclusions: In pediatric liver disease, PT-INR does not reliably reflect global coagulation capacity. Thrombin generation testing provides additional, integrative information on hemostasis and may improve laboratory assessment beyond conventional tests.<\/jats:p>","DOI":"10.3390\/diagnostics16091328","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:09:33Z","timestamp":1777388973000},"page":"1328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Thrombin Generation in Acute and Chronic Liver Disease in Children"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2610-6842","authenticated-orcid":false,"given":"Giovina","family":"Di Felice","sequence":"first","affiliation":[{"name":"Clinical Laboratory Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9618-0007","authenticated-orcid":false,"given":"Anna Lisa","family":"Montemari","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4426-0395","authenticated-orcid":false,"given":"Andrea","family":"Pietrobattista","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases and Hepatology, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Full Member of the European Reference Network Rare Liver, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7313-5960","authenticated-orcid":false,"given":"Luca","family":"Della Volpe","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases and Hepatology, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Full Member of the European Reference Network Rare Liver, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Mosca","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases and Hepatology, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Full Member of the European Reference Network Rare Liver, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0311-5204","authenticated-orcid":false,"given":"Daniela","family":"Liccardo","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases and Hepatology, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Full Member of the European Reference Network Rare Liver, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Pezzi","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1006-5513","authenticated-orcid":false,"given":"Chiara","family":"Giorni","sequence":"additional","affiliation":[{"name":"Pediatric Cardiac Intensive Care Unit, Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Luciani","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danilo","family":"Alunni Fegatelli","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Health and Health Professions, Link Campus University, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6139-7174","authenticated-orcid":false,"given":"Annarita","family":"Vestri","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Sapienza University, Policlinico Umberto I, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5931-8679","authenticated-orcid":false,"given":"Ottavia","family":"Porzio","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"},{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1373\/clinchem.2015.248625","article-title":"Thrombin Generation Assay and Its Application in the Clinical Laboratory","volume":"62","author":"Tripodi","year":"2016","journal-title":"Clin. 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