{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:26:39Z","timestamp":1786926399093,"version":"build-2736575974"},"reference-count":15,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"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":["Int J Lab Hematology"],"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n Bivalirudin is an alternative anticoagulant to heparin and is widely used in pediatric extracorporeal life support (ECLS). Its activity is monitored using activated partial thromboplastin time (aPTT) and\/or more specific tests such as plasma\u2010diluted thrombin time (dTT). A new automated thrombin generation assay (TGA) has also shown promise in evaluating the hemostatic response in anticoagulated patients; however, its utility for monitoring bivalirudin or other anticoagulants in pediatrics remains unknown. We aimed to evaluate TGA in pediatric patients treated with bivalirudin and to compare it with that observed in patients receiving other commonly used anticoagulants.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n TGA, aPTT, aPTT with hepzyme, dTT, INR were measured in 30 specimens from 12 pediatric ECLS patients anticoagulated with bivalirudin. In addition, TGA, anti\u2010Xa assay, and INR were measured in samples from children receiving enoxaparin (\n n<\/jats:italic>\n \u2009=\u200922, 10 patients), heparin (\n n<\/jats:italic>\n \u2009=\u200916, 8 patients), and warfarin (\n n<\/jats:italic>\n \u2009=\u200919, 6 patients).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n TGA lag ratio showed a strong correlation with bivalirudin concentration as measured by dTT and ROC analysis demonstrated that a Lag ratio >\u20092.0 predicted specimens within the therapeutic range for bivalirudin (sensitivity 0.88, specificity 0.67, accuracy 0.79). Interestingly, samples containing endogenous heparin\u2010like substances exhibited paradoxically enhanced thrombin generation, despite having the highest aPTT values. Enoxaparin effect was associated with a reduction in thrombin peak and endogenous thrombin potential (ETP) suppression, while both heparin and warfarin led to a prolonged lag time, along with decreased peak and greater ETP suppression.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n TGA shows promise in evaluating bivalirudin anticoagulation and is capable of detecting anticoagulant activity across both subtherapeutic and therapeutic levels of other agents commonly used in pediatric patients.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/ijlh.70223","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:20:02Z","timestamp":1786926002000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of Thrombin Generation in Pediatric Patients on Extracorporeal Life Support: Impact of Bivalirudin and Other Anticoagulants"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5030-6029","authenticated-orcid":false,"given":"Vadim","family":"Kostousov","sequence":"first","affiliation":[{"name":"Department of Pathology & Immunology Baylor College of Medicine Houston Texas USA"},{"name":"Department of Pathology, Division of Transfusion Medicine & Coagulation Texas Children's Hospital Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2091-4966","authenticated-orcid":false,"given":"Karen","family":"Bruzdoski","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Transfusion Medicine & Coagulation Texas Children's Hospital Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5520-0411","authenticated-orcid":false,"given":"Amir","family":"Navaei","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology Baylor College of Medicine Houston Texas USA"},{"name":"Department of Pediatrics, Division of Critical Care Medicine & Cardiology Baylor College of Medicine Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6124-803X","authenticated-orcid":false,"given":"Jun","family":"Teruya","sequence":"additional","affiliation":[{"name":"Department of Pathology & Immunology Baylor College of Medicine Houston Texas USA"},{"name":"Department of Pathology, Division of Transfusion Medicine & Coagulation Texas Children's Hospital Houston Texas USA"},{"name":"Department of Medicine Baylor College of Medicine Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2023.1237601","article-title":"Is It Time to Switch to Bivalirudin for ECMO Anticoagulation?","volume":"10","author":"Navaei A.","year":"2023","journal-title":"Frontiers in Medicine"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1111\/jth.15529","article-title":"Thrombin Generation Assays Are Versatile Tools in Blood Coagulation Analysis: A Review of Technical Features, and Applications From Research to Laboratory Routine","volume":"19","author":"Depasse F.","year":"2021","journal-title":"Journal of Thrombosis and Haemostasis"},{"issue":"4","key":"e_1_2_12_4_1","doi-asserted-by":"crossref","DOI":"10.1002\/rth2.12523","article-title":"Comparison Is Not Reason: Pitfalls in Reporting Thrombin Generation Results in Anticoagulated Patients","volume":"5","author":"Douxfils J.","year":"2021","journal-title":"Research and Practice in Thrombosis and Haemostasis"},{"key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.thromres.2019.12.007","article-title":"Monitoring Bivalirudin Therapy in Children on Extracorporeal Circulatory Support Devices: Thromboelastometry Versus Routine Coagulation Testing","volume":"186","author":"Teruya J.","year":"2020","journal-title":"Thrombosis Research"},{"key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1111\/ijlh.13780","article-title":"How to Best Monitor Bivalirudin Anticoagulant Effect for ECMO and VAD\u2010Comparison of Four Assay Methods","volume":"44","author":"Teruya J.","year":"2022","journal-title":"International Journal of Laboratory Hematology"},{"key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.thromres.2020.05.020","article-title":"Age\u2010Specific Differences in the in Vitro Anticoagulant Effect of Bivalirudin in Healthy Neonates and Children Compared to Adults","volume":"192","author":"Letunica N.","year":"2020","journal-title":"Thrombosis Research"},{"key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1097\/PCC.0000000000002527","article-title":"Prospective Exploratory Experience With Bivalirudin Anticoagulation in Pediatric Extracorporeal Membrane Oxygenation","volume":"21","author":"Ryerson L. M.","year":"2020","journal-title":"Pediatric Critical Care Medicine"},{"key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"S467","DOI":"10.1016\/j.healun.2020.01.325","article-title":"Coagulation Monitoring Correlation With Bivalirudin Dosing in Pediatric Ventricular Assist Device Support","volume":"39","author":"Knoll C.","year":"2020","journal-title":"Journal of Heart and Lung Transplantation"},{"issue":"6","key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1186\/s13054-014-0636-4","article-title":"Endogenous Glycosaminoglycan Anticoagulation in Extracorporeal Membrane Oxygenation","volume":"18","author":"MacLaren G.","year":"2014","journal-title":"Critical Care"},{"key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1111\/j.1538-7836.2008.02963.x","article-title":"Microparticle\u2010Mediated Thrombin Generation Assay: Increased Activity in Patients With Recurrent Thrombosis","volume":"6","author":"Bidot L.","year":"2008","journal-title":"Journal of Thrombosis and Haemostasis"},{"key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1097\/TA.0b013e31825b5c10","article-title":"Endothelial Glycocalyx Degradation Induces Endogenous Heparinization in Patients With Severe Injury and Early Traumatic Coagulopathy","volume":"73","author":"Ostrowski S. R.","year":"2012","journal-title":"Journal of Trauma and Acute Care Surgery"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1002\/rth2.12340","article-title":"Direct Oral Anticoagulant Plasma Levels and Thrombin Generation on ST Genesia System","volume":"4","author":"Pfrepper C.","year":"2020","journal-title":"Research and Practice in Thrombosis and Haemostasis"},{"key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1002\/rth2.12497","article-title":"Anticoagulated Patients Exhibit Intact Endogenous Thrombin Potential Using ST Genesia Unlike the Calibrated Automated Thrombogram","volume":"5","author":"Helin T. A.","year":"2021","journal-title":"Research and Practice in Thrombosis and Haemostasis"},{"key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1111\/ijlh.13836","article-title":"Monitoring of Heparin Therapy Beyond the Anti\u2010Xa Activity Assay: Evaluation of a Thrombin Generation Assay","volume":"44","author":"Vermeiren P.","year":"2022","journal-title":"International Journal of Laboratory Hematology"},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1160\/TH05-10-0685","article-title":"Age\u2010Dependency of Thrombin Generation Measured by Means of Calibrated Automated Thrombography (CAT)","volume":"95","author":"Haidl H.","year":"2006","journal-title":"Thrombosis and Haemostasis"}],"container-title":["International Journal of Laboratory Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ijlh.70223","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ijlh.70223","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ijlh.70223","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:20:09Z","timestamp":1786926009000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ijlh.70223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,16]]},"references-count":15,"alternative-id":["10.1111\/ijlh.70223"],"URL":"https:\/\/doi.org\/10.1111\/ijlh.70223","archive":["Portico"],"relation":{},"ISSN":["1751-5521","1751-553X"],"issn-type":[{"value":"1751-5521","type":"print"},{"value":"1751-553X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,16]]},"assertion":[{"value":"2025-10-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ijlh.70223"}}