Anticoagulation and Bleeding during Veno-Venous Extracorporeal Membrane Oxygenation: Insights from the PROTECMO Study

Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, while bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: 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 8471 days on ECMO were analyzed. Unfractionated heparin (UFH) was the initial anticoagulant in 77% of patients, and the most used anticoagulant during the ECMO course (6221 days, 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (39-61), but dropped by 5.3 seconds after the first bleeding event (95% CI -7.4 to -3.2, p< 0.01). Bleeding occurred on 1202 days (16.5 %). Overall, 342 patients (52.5 %) experienced at least one bleeding event (one episode every 215 hours 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 seconds 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.