Anticoagulation and Bleeding during Veno-Venous Extracorporeal Membrane Oxygenation: Insights from the PROTECMO Study
Gennaro Martucci, Marco Giani, Matthieu Schmidt, Kenichi A. Tanaka, Ali Tabatabai, Fabio Tuzzolino, Cara Agerstrand, Jordi Riera, Raj Ramanan, Giacomo Grasselli, Ali Ait Hssain, Whitney D. Gannon, S. Buabbas, Vojka Gorjup, Brian Trethowan, Monica Rizzo, Vito Fanelli, Kyeongman Jeon, Gennaro De Pascale, Alain Combes, Marco Ranieri, Thibault Duburcq, Giuseppe Foti, Juan Ignacio Chico‐Carballas, Martin Balík, Lars Mikael Broman, Peter Schellongowski, Hergen Buscher, Roberto Lorusso, Daniel Brodie, Antonio Arcadipane
Abstract
Abstract 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.