{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T20:22:58Z","timestamp":1787689378122,"version":"build-2784847793"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate whether an activated clotting time (ACT)-guided, formula-based anticoagulation strategy supported by viscoelastic coagulation monitoring (ROTEM) improves perioperative coagulation management and reduces bleeding compared with standard weight-based heparin dosing in patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this single-centre prospective, randomized controlled trial, 100 adults undergoing isolated CABG with CPB were allocated to ACT-guided management (n\u2009=\u200950) or standard care (n\u2009=\u200950). The ACT-guided group received individualized heparin and protamine dosing calculated using predefined ACT-based formulas targeting ACT \u2265400\u2009seconds. The control group received a fixed heparin bolus (300\u2009IU\/kg) with empirical protamine reversal. ROTEM was performed preoperatively, intraoperatively, and postoperatively. The primary end-point was total chest drain output at 24\u2009hours. Secondary end-points included transfusion requirements, thrombotic events, platelet count variation, oxygenator performance, additional heparin or protamine use, ROTEM-derived parameters, and perioperative clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The ACT-guided group had lower 24-hour chest drain bleeding and reduced total exposure to heparin and protamine. Intraoperative ACT values were more consistently within target range, with fewer supplemental heparin doses required. ROTEM demonstrated shorter clotting times and improved clot firmness, indicating reduced postoperative hypocoagulability. Platelet decline during CPB was attenuated. Transfusion rates (28% vs 52%, P\u2009=\u2009.01) and total allogeneic units transfused (0.6\u2009\u00b1\u20091.0 vs 1.4\u2009\u00b1\u20091.6, P\u2009=\u2009.003) were significantly lower, with no observed increase in thrombotic events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Activated clotting time-guided, formula-based anticoagulation supported by ROTEM was associated with more favourable coagulation parameters and reduced bleeding without evidence of increased thrombotic complications within the limitations of the study sample size. Larger prospective studies are warranted to confirm these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/icvts\/ivag197","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:43:47Z","timestamp":1783424627000},"source":"Crossref","is-referenced-by-count":0,"title":["Optimizing Heparin and Protamine Dosing During Cardiopulmonary Bypass Using Activated Clotting Time-Guided Protocols: A Single-Centre Prospective Randomized Controlled Trial"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6181-9480","authenticated-orcid":false,"given":"Youssef","family":"El Dsouki","sequence":"first","affiliation":[{"name":"Maastricht University Medical Centre MUMC , Maastricht 6229 HX,","place":["The Netherlands"]},{"name":"Cardiovascular Research Centre Maastricht CARIM , Maastricht 6229 ER,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1192-1908","authenticated-orcid":false,"given":"Ignazio","family":"Condello","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery, University of Insubria , Varese 21100,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orhan Eren","family":"Gunertem","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Medical Park Hospital, YIH University , Ankara 06680,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abducelil","family":"Yildirim","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Medical Park Hospital, YIH University , Ankara 06680,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serdar","family":"Gunaydin","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Medical Park Hospital, YIH University , Ankara 06680,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1777-2045","authenticated-orcid":false,"given":"Roberto","family":"Lorusso","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Centre MUMC , Maastricht 6229 HX,","place":["The Netherlands"]},{"name":"Cardiovascular Research Centre Maastricht CARIM , Maastricht 6229 ER,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"2026082516011476100_ivag197-B1","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1053\/j.jvca.2016.04.005","article-title":"An adjusted calculation model of reduced heparin doses in cardiopulmonary bypass surgery in a Chinese population","volume":"30","author":"Zhang","year":"2016","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"2026082516011476100_ivag197-B2","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1097\/EJA.0000000000000784","article-title":"Adjusted calculation model of heparin management during cardiopulmonary bypass in obese patients: a randomised controlled trial","volume":"35","author":"Vienne","year":"2018","journal-title":"Eur J Anaesthesiol"},{"key":"2026082516011476100_ivag197-B3","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1007\/s11239-019-01987-7","article-title":"Identifying optimal heparin management during cardiopulmonary bypass in Chinese people: a retrospective observational comparative study","volume":"49","author":"Gan","year":"2020","journal-title":"J Thromb Thrombolysis"},{"key":"2026082516011476100_ivag197-B4","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1345\/aph.1E524","article-title":"Anticoagulation monitoring part 2: unfractionated heparin and low-molecular-weight heparin","volume":"39","author":"Spinler","year":"2005","journal-title":"Ann Pharmacother"},{"key":"2026082516011476100_ivag197-B5","doi-asserted-by":"publisher","first-page":"2088","DOI":"10.3390\/medicina61122088","article-title":"Heparin resistance in cardiac surgery with cardiopulmonary bypass: mechanisms, clinical implications, and evidence-based management","volume":"61","author":"Rivera Jim\u00e9nez","year":"2025","journal-title":"Medicina (Kaunas, Lithuania)"},{"key":"2026082516011476100_ivag197-B6","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1002\/ajh.23599","article-title":"TEG and ROTEM: technology and clinical applications","volume":"89","author":"Whiting","year":"2014","journal-title":"Am J Hematol"},{"key":"2026082516011476100_ivag197-B7","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1111\/bjh.14148","article-title":"The utility of thromboelastography in inherited and acquired bleeding disorders","volume":"174","author":"Nogami","year":"2016","journal-title":"Br J Haematol"},{"key":"2026082516011476100_ivag197-B8","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1097\/TA.0000000000002944","article-title":"Thromboelastography and rotational thromboelastometry in bleeding patients with coagulopathy: practice management guideline from the Eastern Association for the Surgery of Trauma","volume":"89","author":"Bugaev","year":"2020","journal-title":"J Trauma Acute Care Surg"},{"key":"2026082516011476100_ivag197-B9","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1055\/s-0037-1609019","article-title":"Is 300 seconds ACT safe and efficient during MiECC procedures?","volume":"67","author":"Bauer","year":"2019","journal-title":"Thorac Cardiovasc Surg"},{"key":"2026082516011476100_ivag197-B10","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1177\/02676591231204284","article-title":"Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery on minimal invasive extracorporeal circulation; a prospective randomized study","volume":"39","author":"Gkiouliava","year":"2024","journal-title":"Perfusion"},{"key":"2026082516011476100_ivag197-B11","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1053\/j.jvca.2013.10.026","article-title":"Heparinase thromboelastography compared with activated coagulation time for protamine titration after cardiopulmonary bypass","volume":"28","author":"Levin","year":"2014","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"2026082516011476100_ivag197-B12","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S0022-5223(19)41500-6","article-title":"Heparin therapy during extracorporeal circulation. II. The use of a dose-response curve to individualize heparin and protamine dosage","volume":"69","author":"Bull","year":"1975","journal-title":"J Thorac Cardiovasc Surg"},{"key":"2026082516011476100_ivag197-B13","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1051\/ject\/201345235","article-title":"Method to calculate the protamine dose necessary for reversal of heparin as a function of activated clotting time in patients undergoing cardiac surgery","volume":"45","author":"Su\u00e1rez Cuenca","year":"2013","journal-title":"J Extra Corpor Technol"},{"key":"2026082516011476100_ivag197-B14","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1051\/ject\/2023026","article-title":"Protamine dose to neutralize heparin at the completion of cardiopulmonary bypass can be reduced significantly without affecting post-operative bleeding","volume":"55","author":"Lee","year":"2023","journal-title":"J Extra Corpor Technol"},{"key":"2026082516011476100_ivag197-B15","doi-asserted-by":"publisher","first-page":"178","DOI":"10.4103\/aca.ACA_26_19","article-title":"Less is more: we are administering too much protamine in cardiac surgery","volume":"24","author":"De Simone","year":"2021","journal-title":"Ann Card Anaesth"},{"key":"2026082516011476100_ivag197-B16","doi-asserted-by":"publisher","first-page":"2369","DOI":"10.1053\/j.jvca.2019.12.046","article-title":"In vivo protamine titration using activated coagulation time to neutralize heparin anticoagulation in cardiac surgery: proof of concept","volume":"34","author":"Rochon","year":"2020","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"2026082516011476100_ivag197-B17","first-page":"165","article-title":"Automated protamine dose assay in heparin reversal management after cardiopulmonary by pass","volume":"67","author":"Guarracino","year":"2001","journal-title":"Minerva Anestesiol"},{"key":"2026082516011476100_ivag197-B18","doi-asserted-by":"publisher","first-page":"e54144","DOI":"10.7759\/cureus.54144","article-title":"Comparison of blood concentration and weight-based heparin and protamine dosing strategies for cardiopulmonary bypass: a systematic review and meta-analysis","volume":"16","author":"Raner","year":"2024","journal-title":"Cureus"},{"key":"2026082516011476100_ivag197-B19","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.bja.2018.01.023","article-title":"Anticoagulant and side-effects of protamine in cardiac surgery: a narrative review","volume":"120","author":"Boer","year":"2018","journal-title":"Br J Anaesth"},{"key":"2026082516011476100_ivag197-B20","doi-asserted-by":"publisher","first-page":"3447","DOI":"10.1053\/j.jvca.2022.03.042","article-title":"Coagulation and transfusion updates from 2021","volume":"36","author":"Fabbro","year":"2022","journal-title":"J Cardiothorac Vasc Anesth"},{"key":"2026082516011476100_ivag197-B21","doi-asserted-by":"publisher","first-page":"38","DOI":"10.3390\/clinpract15020038","article-title":"Effects of protamine reversal on coagulation parameters after high-dose heparin administration in percutaneous hepatic chemosaturation intervention","volume":"15","author":"Metze","year":"2025","journal-title":"Clin Pract"},{"key":"2026082516011476100_ivag197-B22","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1053\/j.jvca.2011.09.021","article-title":"Increased chest tube drainage is independently associated with adverse outcome after cardiac surgery","volume":"26","author":"Christensen","year":"2012","journal-title":"J Cardiothorac Vasc Anesth"}],"container-title":["Interdisciplinary CardioVascular and Thoracic Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/icvts\/advance-article-pdf\/doi\/10.1093\/icvts\/ivag197\/68732298\/ivag197.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/icvts\/article-pdf\/41\/8\/ivag197\/68732298\/ivag197.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/icvts\/article-pdf\/41\/8\/ivag197\/68732298\/ivag197.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T20:01:17Z","timestamp":1787688077000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/icvts\/article\/doi\/10.1093\/icvts\/ivag197\/8728798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,8]]},"references-count":22,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,3]]}},"URL":"https:\/\/doi.org\/10.1093\/icvts\/ivag197","relation":{},"ISSN":["2753-670X"],"issn-type":[{"value":"2753-670X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,7,8]]},"article-number":"ivag197"}}