Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, whereas bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: This was an international prospective observational study in 41 centers, from December 2018 to February 2021. Anticoagulation was recorded daily in terms of type, dosage, and monitoring strategy. Bleeding events were reported according to site, severity, and impact on mortality. Measurements and Main Results: The study cohort included 652 patients, and 8,471 days on ECMO were analyzed. Unfractionated heparin was the initial anticoagulant in 77% of patients, and the most frequently used anticoagulant during the ECMO course (6,221 d; 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (interquartile range, 39 to 61 s) but dropped by 5.3 seconds after the first bleeding event (95% confidence interval, -7.4 to -3.2; P < 0.01). Bleeding occurred on 1,202 days (16.5%). Overall, 342 patients (52.5%) experienced at least one bleeding event (one episode every 215 h on ECMO), of which 10 (1.6%) were fatal. In a multiple penalized Cox proportional hazard model, higher aPTT was a potentially modifiable risk factor for the first episode of bleeding (for 20-s increase; hazard ratio, 1.07). Conclusions: Anticoagulation during VV ECMO was a dynamic process, with frequent stopping in cases of bleeding and restart according to the clinical picture. Future studies might explore lower aPTT targets to reduce the risk of bleeding.

1st Medical Faculty General University Hospital Prague Czech Republic

Alma Mater Studiorum University of Bologna Bologna Italy

Cardiothoracic Surgery Department Maastricht University Medical Center and

Cardiovascular Research Institute Maastricht Maastricht University Maastricht the Netherlands

Centre Hospitalier Regional Universitaire Lille Hôpital Roger Salengro Lille France

Centro de Investigacion en Red de Enfermedades Respiratorias Instituto de Salud Carlos 3 Barcelona Spain

Critical Care Department Alvaro Cunqueiro University Hospital Vigo Spain

Critical Care Department Hospital Universitari Vall d'Hebron Barcelona Spain

Department of Allergy Pulmonary and Critical Care Medicine Vanderbilt University Medical Center Nashville Tennessee

Department of Anesthesia and Intensive Care and

Department of Anesthesia Critical Care and Emergency Città della Salute e della Scienza Hospital University of Turin Turin Italy

Department of Anesthesia Intensive Care and Emergency Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy

Department of Critical Care Medicine University of Pittsburgh Pittsburgh Pennsylvania

Department of Medicine 1 Intensive Care Unit 13i2 Center of Excellence in Medical Intensive Care Medical University of Vienna Vienna Austria

Department of Medicine and Center for Acute Respiratory Failure Irving Medical Center Columbia University New York New York

Department of Medicine School of Medicine Johns Hopkins University Baltimore Maryland

Department of Pathophysiology and Transplantation University of Milan Milan Italy

Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden

Department of Surgical Sciences and

Dipartimento di Scienze Biotecnologiche di Base Cliniche Intensivologiche e Perioperatorie Università Cattolica del Sacro Cuore Rome Italy

Dipartimento di Scienze dell'Emergenza Anestesiologiche e della Rianimazione Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy

ECMO Center Ljubljana Slovenia

ECMO Centre Karolinska Karolinska University Hospital Stockholm Sweden

Fondazione IRCCS San Gerardo dei Tintori Università degli Studi di Milano Bicocca Monza Italy

Hamad Medical Corporation Doha Qatar

Kuwait Extracorporeal Life Support Program Jaber Al Ahmad Alsabah Hospital Kuwait City Kuwait

Meijer Heart Center Butterworth Hospital Spectrum Health Grand Rapids Michigan

Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea

Service de Médecine Intensive Réanimation Institut de Cardiologie Assistance Publique Hôpitaux de Paris Hôpital Pitié Salpêtrière Paris France

Shock Organ Dysfunction and Resuscitation Vall d'Hebron Institut de Recerca Barcelona Spain

Sorbonne University Institute of Cardiometabolism and Nutrition Paris France

St Vincent's Hospital Sydney University of New South Wales Sydney New South Wales Australia

Statistics and Data Management Services Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione Palermo Italy

The University of Oklahoma Health Sciences Center University of Oklahoma Oklahoma City Oklahoma

University of Maryland St Joseph Medical Center Towson Maryland

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