{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:40:24Z","timestamp":1790678424452,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: We aimed to investigate the relationship between anti-activated Factor X (anti-FXa) and activated Partial Thromboplastin Time (aPTT), and its modulation by other haemostasis co-variables during veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. We further investigated their association with serious bleeding and thrombotic complications. Methods: This retrospective single-center study included 265 adults supported by VA-ECMO for refractory cardiogenic shock from January 2015 to June 2019. The concordance of anti-FXa and aPTT and their correlations were assessed in 1699 paired samples. Their independent associations with serious bleeding or thrombotic complications were also analysed in multivariate analysis. Results: The concordance rate of aPTT with anti-FXa values was 50.7%, with 39.3% subtherapeutic aPTT values. However, anti-FXa and aPTT remained associated (\u03b2 = 0.43 (95% CI 0.4\u20130.45) 10\u22122 IU\/mL, p &lt; 0.001), with a significant modulation by several biological co-variables. There was no association between anti-FXa nor aPTT values with serious bleeding or with thrombotic complications. Conclusion: During VA-ECMO, although anti-FXa and aPTT were significantly associated, their values were highly discordant with marked sub-therapeutic aPTT values. These results should favour the use of anti-FXa. The effect of biological co-variables and the failure of anti-FXa and aPTT to predict bleeding and thrombotic complications underline the complexity of VA-ECMO-related coagulopathy.<\/jats:p>","DOI":"10.3390\/jcm10102158","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T04:25:07Z","timestamp":1621225507000},"page":"2158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Evaluation of Anti-Activated Factor X Activity and Activated Partial Thromboplastin Time Relations and Their Association with Bleeding and Thrombosis during Veno-Arterial ECMO Support: A Retrospective Study"],"prefix":"10.3390","volume":"10","author":[{"given":"Mouhamed Djahoum","family":"Moussa","sequence":"first","affiliation":[{"name":"CHU Lille, P\u00f4le d\u2019Anesth\u00e9sie-R\u00e9animation, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Soquet","sequence":"additional","affiliation":[{"name":"CHU Lille, Service de Chirurgie Cardiaque, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9546-1808","authenticated-orcid":false,"given":"Antoine","family":"Lamer","sequence":"additional","affiliation":[{"name":"CHU Lille, P\u00f4le d\u2019Anesth\u00e9sie-R\u00e9animation, 59000 Lille, France"},{"name":"Univ. Lille, INSERM, CHU Lille, CIC-IT 1403, 59000 Lille, France"},{"name":"Univ. Lille, CHU Lille, ULR 2694-METRICS: \u00c9valuation des Technologies de Sant\u00e9 et des Pratiques M\u00e9dicales, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Labreuche","sequence":"additional","affiliation":[{"name":"Univ. Lille, CHU Lille, ULR 2694-METRICS: \u00c9valuation des Technologies de Sant\u00e9 et des Pratiques M\u00e9dicales, 59000 Lille, France"},{"name":"CHU Lille, Department of Biostatistics, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Gantois","sequence":"additional","affiliation":[{"name":"CHU Lille, P\u00f4le d\u2019Anesth\u00e9sie-R\u00e9animation, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabelle","family":"Dupont","sequence":"additional","affiliation":[{"name":"CHU Lille, P\u00f4le d\u2019H\u00e9matologie-Transfusion, Centre de Biologie Pathologie G\u00e9n\u00e9tique, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-716X","authenticated-orcid":false,"given":"Osama","family":"Abou-Arab","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Amiens University Hospital, 80054 Amiens, France"},{"name":"MP3CV, EA7517, CURS, Jules Verne University of Picardie, 80054 Amiens, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2837-4285","authenticated-orcid":false,"given":"Natacha","family":"Rousse","sequence":"additional","affiliation":[{"name":"CHU Lille, Service de Chirurgie Cardiaque, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Liu","sequence":"additional","affiliation":[{"name":"CHU Lille, P\u00f4le d\u2019Anesth\u00e9sie-R\u00e9animation, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Brandt","sequence":"additional","affiliation":[{"name":"CHU Lille, P\u00f4le d\u2019Anesth\u00e9sie-R\u00e9animation, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Foulon","sequence":"additional","affiliation":[{"name":"CHU Lille, P\u00f4le d\u2019Anesth\u00e9sie-R\u00e9animation, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Leroy","sequence":"additional","affiliation":[{"name":"CHU Lille, P\u00f4le d\u2019Anesth\u00e9sie-R\u00e9animation, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Schurtz","sequence":"additional","affiliation":[{"name":"CHU Lille, P\u00f4le de Cardiologie, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Jeanpierre","sequence":"additional","affiliation":[{"name":"CHU Lille, P\u00f4le d\u2019H\u00e9matologie-Transfusion, Centre de Biologie Pathologie G\u00e9n\u00e9tique, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Duhamel","sequence":"additional","affiliation":[{"name":"Univ. Lille, CHU Lille, ULR 2694-METRICS: \u00c9valuation des Technologies de Sant\u00e9 et des Pratiques M\u00e9dicales, 59000 Lille, France"},{"name":"CHU Lille, Department of Biostatistics, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5953-163X","authenticated-orcid":false,"given":"Sophie","family":"Susen","sequence":"additional","affiliation":[{"name":"CHU Lille, P\u00f4le d\u2019H\u00e9matologie-Transfusion, Centre de Biologie Pathologie G\u00e9n\u00e9tique, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Vincentelli","sequence":"additional","affiliation":[{"name":"CHU Lille, Service de Chirurgie Cardiaque, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Robin","sequence":"additional","affiliation":[{"name":"CHU Lille, P\u00f4le d\u2019Anesth\u00e9sie-R\u00e9animation, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1177\/0267659118766435","article-title":"Intracranial Hemorrhage in Adults on ECMO","volume":"33","author":"Cavayas","year":"2018","journal-title":"Perfusion"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1177\/0267659118814690","article-title":"Prognostic Impact of Blood Product Transfusion in VA and VV ECMO","volume":"34","author":"Anselmi","year":"2019","journal-title":"Perfusion"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1053\/j.jvca.2018.07.045","article-title":"Bleeding, Thrombosis, and Transfusion with Two Heparin Anticoagulation Protocols in Venoarterial ECMO Patients","volume":"33","author":"Mazzeffi","year":"2019","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13613-016-0196-7","article-title":"Predictive Factors of Bleeding Events in Adults Undergoing Extracorporeal Membrane Oxygenation","volume":"6","author":"Aubron","year":"2016","journal-title":"Ann. Intensive Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"222ra17","DOI":"10.1126\/scitranslmed.3006804","article-title":"A Factor XIIa Inhibitory Antibody Provides Thromboprotection in Extracorporeal Circulation without Increasing Bleeding Risk","volume":"6","author":"Larsson","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_6","first-page":"1","article-title":"Flow-Induced Platelet Activation in Components of the Extracorporeal Membrane Oxygenation","volume":"8","author":"Fuchs","year":"2018","journal-title":"Circuit. Sci. Rep."},{"key":"ref_7","unstructured":"(2021, February 20). ELSO Guidelines General All ECLS Version1.4 Pdf. Available online: https:\/\/www.elso.org\/Resources\/Guidelines.aspx."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1055\/s-0037-1606179","article-title":"Bleeding and Thrombotic Complications in the Use of Extracorporeal Membrane Oxygenation","volume":"44","author":"Thomas","year":"2018","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_9","unstructured":"Lequier, L., Annich, G., and Al-Ibrahim, O. (2021, February 20). ELSO Anticoagulation Guideline. 2014. Extracorpor. Life Support Organ. ELSO 2016, 1\u201317. Available online: https:\/\/www.elso.org\/Resources\/Guidelines.aspx."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1093\/ejcts\/ezaa283","article-title":"2020 EACTS\/ELSO\/STS\/AATS Expert Consensus on Post-Cardiotomy Extracorporeal Life Support in Adult Patients","volume":"59","author":"Lorusso","year":"2021","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e175","DOI":"10.1097\/PCC.0000000000000101","article-title":"Unfractionated Heparin Activity Measured by Anti-Factor Xa Levels Is Associated with the Need for Extracorporeal Membrane Oxygenation Circuit\/Membrane Oxygenator Change: A Retrospective Pediatric Study","volume":"15","author":"Irby","year":"2014","journal-title":"Pediatr. Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1177\/0885066618776937","article-title":"Anticoagulation Monitoring under ECMO Support: A Comparative Study between the Activated Coagulation Time and the Anti-Xa Activity Assay","volume":"35","author":"Delmas","year":"2020","journal-title":"J. Intensive Care Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1002\/j.1875-9114.2011.01049.x","article-title":"Antifactor Xa Levels versus Activated Partial Thromboplastin Time for Monitoring Unfractionated Heparin","volume":"32","author":"Vandiver","year":"2012","journal-title":"Pharmacotherapy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.5858\/arpa.2013-0572-OA","article-title":"The Influence of Free Hemoglobin and Bilirubin on Heparin Monitoring by Activated Partial Thromboplastin Time and Anti-Xa Assay","volume":"138","author":"Kostousov","year":"2014","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1097\/ALN.0000000000003044","article-title":"Anticoagulation Management and Antithrombin Supplementation Practice during Veno-Venous Extracorporeal Membrane Oxygenation: A Worldwide Survey","volume":"132","author":"Protti","year":"2020","journal-title":"Anesthesiology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1055\/s-0038-1656312","article-title":"Diurnal Rhythm in Anticoagulant Effect of Heparin during a Low Dose Constant Rate Infusion. A Study in Healthy Volunteers","volume":"68","author":"Krulder","year":"1992","journal-title":"Thromb. Haemost."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"541","DOI":"10.2307\/2530374","article-title":"The Analysis of Failure Times in the Presence of Competing Risks","volume":"34","author":"Prentice","year":"1978","journal-title":"Biometrics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e24S","DOI":"10.1378\/chest.11-2291","article-title":"Parenteral Anticoagulants","volume":"141","author":"Garcia","year":"2012","journal-title":"Chest"},{"key":"ref_19","unstructured":"Marlar, R.A. (2008). Clinical and Laboratory Standards Institute One-Stage Prothrombin Time (PT) Test and Activated Partial Thromboplastin Time (APTT) Test: Approved Guideline, Clinical and Laboratory Standards Institute."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Therneau, T.M., and Grambsch, P.M. (2000). Multiple Events per Subject. Modeling Survival Data: Extending the Cox Model, Springer. Statistics for Biology and Health.","DOI":"10.1007\/978-1-4757-3294-8"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1076029619876030","DOI":"10.1177\/1076029619876030","article-title":"Evaluation of Antifactor-Xa Heparin Assay and Activated Partial Thromboplastin Time Values in Patients on Therapeutic Continuous Infusion Unfractionated Heparin Therapy","volume":"25","author":"McLaughlin","year":"2019","journal-title":"Clin. Appl. Thromb."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.jchf.2014.11.009","article-title":"Anti-Factor Xa and Activated Partial Thromboplastin Time Measurements for Heparin Monitoring in Mechanical Circulatory Support","volume":"3","author":"Adatya","year":"2015","journal-title":"JACC Heart Fail."},{"key":"ref_23","first-page":"253","article-title":"Activated Partial Thromboplastin Time Monitoring of Unfractionated Heparin Therapy: Issues and Recommendations","volume":"43","author":"Marlar","year":"2017","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_24","first-page":"37","article-title":"Platelet-Derived Microparticles Generated by Neonatal Extracorporeal Membrane Oxygenation Systems","volume":"61","author":"Meyer","year":"2015","journal-title":"ASAIO J. Am. Soc. Artif. Intern. Organs 1992"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1053\/j.jvca.2018.11.031","article-title":"Von Willebrand Factor-GP1b\u03b1 Interactions in Venoarterial Extracorporeal Membrane Oxygenation Patients","volume":"33","author":"Mazzeffi","year":"2019","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_26","first-page":"1076029620982374","article-title":"Device-Induced Hemostatic Disorders in Mechanically Assisted Circulation","volume":"27","author":"Wang","year":"2021","journal-title":"Clin. Appl. Thromb. Off. J. Int. Acad. Clin. Appl. Thromb."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.bbrc.2004.05.166","article-title":"Pathologic High Shear Stress Induces Apoptosis Events in Human Platelets","volume":"320","author":"Leytin","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9204","DOI":"10.1074\/jbc.M116.766196","article-title":"Evidence for Shear-Mediated Ca2+ Entry through Mechanosensitive Cation Channels in Human Platelets and a Megakaryocytic Cell Line","volume":"292","author":"Ilkan","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1111\/j.1538-7836.2009.03653.x","article-title":"The Glycoprotein Ibalpha-von Willebrand Factor Interaction Induces Platelet Apoptosis","volume":"8","author":"Li","year":"2010","journal-title":"J. Thromb. Haemost. JTH"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"114","DOI":"10.3389\/fcvm.2019.00114","article-title":"Platelet Function During Extracorporeal Membrane Oxygenation in Adult Patients","volume":"6","author":"Balle","year":"2019","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.athoracsur.2015.07.046","article-title":"Bleeding, Transfusion, and Mortality on Extracorporeal Life Support: ECLS Working Group on Thrombosis and Hemostasis","volume":"101","author":"Mazzeffi","year":"2016","journal-title":"Ann. Thorac. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s13054-021-03554-0","article-title":"Anti-Xa Activity and Hemorrhagic Events under Extracorporeal Membrane Oxygenation (ECMO): A Multicenter Cohort Study","volume":"25","author":"Descamps","year":"2021","journal-title":"Crit. Care Lond. Engl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1213\/ANE.0000000000000554","article-title":"Extracorporeal Membrane Oxygenation Induces Short-Term Loss of High-Molecular-Weight von Willebrand Factor Multimers","volume":"120","author":"Tauber","year":"2015","journal-title":"Anesth. Analg."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Frimat, M., Boudhabhay, I., and Roumenina, L.T. (2019). Hemolysis Derived Products Toxicity and Endothelium: Model of the Second Hit. Toxins, 11.","DOI":"10.3390\/toxins11110660"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1182\/blood-2002-05-1550","article-title":"Aspects of Hydrodynamic Shear Regulating Shear-Induced Platelet Activation and Self-Association of von Willebrand Factor in Suspension","volume":"101","author":"Shankaran","year":"2003","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1097\/01.mbc.0000164424.90545.6e","article-title":"Effects of Pre-Analytical Variables on the Anti-Activated Factor X Chromogenic Assay When Monitoring Unfractionated Heparin and Low Molecular Weight Heparin Anticoagulation. Blood Coagul","volume":"16","author":"McGlasson","year":"2005","journal-title":"Fibrinolysis"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1055\/s-0038-1677018","article-title":"How to Optimize Activated Partial Thromboplastin Time (APTT) Testing: Solutions to Establishing and Verifying Normal Reference Intervals and Assessing APTT Reagents for Sensitivity to Heparin, Lupus Anticoagulant, and Clotting Factors","volume":"45","author":"Favaloro","year":"2019","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1538-7836.2008.03224.x","article-title":"Interlaboratory Agreement in the Monitoring of Unfractionated Heparin Using the Anti-Factor Xa-Correlated Activated Partial Thromboplastin Time","volume":"7","author":"Cuker","year":"2009","journal-title":"J. Thromb. Haemost."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1056\/NEJMoa1800385","article-title":"Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome","volume":"378","author":"Combes","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1080\/09537104.2018.1492109","article-title":"Platelet Aggregation Measured by Single-Platelet Counting and Using PFA-100 Devices","volume":"29","author":"Dovlatova","year":"2018","journal-title":"Platelets"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13613-017-0352-8","article-title":"Thromboelastography-Based Anticoagulation Management during Extracorporeal Membrane Oxygenation: A Safety and Feasibility Pilot Study","volume":"8","author":"Panigada","year":"2018","journal-title":"Ann. Intensive Care"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1213\/ANE.0000000000004275","article-title":"Coagulation Factor Levels and Underlying Thrombin Generation Patterns in Adult Extracorporeal Membrane Oxygenation Patients","volume":"129","author":"Mazzeffi","year":"2019","journal-title":"Anesth. Analg."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/10\/2158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:02:26Z","timestamp":1760162546000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/10\/2158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,17]]},"references-count":42,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["jcm10102158"],"URL":"https:\/\/doi.org\/10.3390\/jcm10102158","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,17]]}}}