Impact of bleeding and thrombosis on outcome of 945 COVID-19 VV-ECMO cases from a German registry

Johannes Herrmann^1*Janno Schade¹Patrick Meybohm¹Noah Paschke¹Martha Huebsch¹Quirin Notz¹Julie Groene¹Daniel Roeder¹Peter Kranke¹Michaela Merten²Micha Landoll²Peter Spieth³Stefan Kluge⁴Dominik Jarczak⁴Kevin Roedl⁴Michael Sonntagbauer⁴Christian Putensen⁵Jens-Christian Schewe⁵Stefan Ehrentraut⁵Stefan Kreyer⁵Andreas Wehrfritz⁶Ixchel Castellanos⁶Karl Bihlmaier⁶Karsten Schmidt⁷Thorsten Brenner⁷Frank Herbstreit⁷Florian Espeter⁷Jan Wiefhoff⁷Richard Ellerkmann⁸Daniel Oswald⁹Bjoern Ellger⁹Gösta Lotz¹⁰Florian J. Raimann¹⁰Tobias Wengenmayer¹¹Dawid L. Staudacher¹¹Viviane Zotzmann¹¹Onnen Moerer¹²Christian Kühn¹³Matthias Kochanek¹⁴Ralf Muellenbach¹⁵Patricia Glaser¹⁶Falk Fichtner¹⁷Marc Bodenstein¹⁸Michael Findeisen¹⁹Vanessa Rembold¹⁹Markus Heim²⁰Gerhard Schneider²⁰Tobias Lahmer²⁰Jan-Sören Padberg²¹Carsten Hullermann²¹Philipp M Lepper²²Andre P Becker²²Guy Danziger²²Carlos Metz²²Peter Rosenberger²³Valbona Mirakaj²³Alice-Marie Bernard²³Stephan Braune²⁴Rebecca Roth²⁵Anna Grau²⁵Peter Heuschmann²⁵Christian Karagiannidis²Christopher Lotz¹

• ¹University Hospital Würzburg, Würzburg, Germany
• ²Krankenhaus Koln-Merheim, Cologne, Germany
• ³Technische Universitat Dresden, Dresden, Germany
• ⁴Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany
• ⁵Universitatsklinikum Bonn, Bonn, Germany
• ⁶Universitatsklinikum Erlangen, Erlangen, Germany
• ⁷Universitat Duisburg-Essen, Duisburg, Germany
• ⁸Universitat Witten/Herdecke, Witten, Germany
• ⁹Klinikum Westfalen GmbH, Dortmund, Germany
• ¹⁰Universitatsklinikum Frankfurt, Frankfurt, Germany
• ¹¹Universitatsklinikum Freiburg, Freiburg, Germany
• ¹²Universitatsmedizin Gottingen, Göttingen, Germany
• ¹³Medizinische Hochschule Hannover, Hanover, Germany
• ¹⁴Universitatsklinikum Koln, Cologne, Germany
• ¹⁵Klinikum Kassel GmbH, Kassel, Germany
• ¹⁶Asklepios Kliniken Langen Seligenstadt GmbH Asklepios Klinik Langen, Langen, Germany
• ¹⁷Universitatsklinikum Leipzig, Leipzig, Germany
• ¹⁸Universitatsmedizin der Johannes Gutenberg-Universitat Mainz, Mainz, Germany
• ¹⁹Munchen Klinik Harlaching, Munich, Germany
• ²⁰Klinikum rechts der Isar der Technischen Universitat Munchen, Munich, Germany
• ²¹Universitatsklinikum Munster, Münster, Germany
• ²²Universitatsklinikum des Saarlandes, Homburg, Germany
• ²³Universitatsklinikum Tubingen, Tübingen, Germany
• ²⁴St Franziskus-Hospital Munster GmbH, Münster, Germany
• ²⁵Julius-Maximilians-Universitat Wurzburg, Würzburg, Germany

Bleeding and thromboembolic events (BTE) increase the mortality of COVID-19 acute respiratory distress syndrome (ARDS) treated with extracorporeal membrane oxygenation (ECMO). The current analysis aimed to assess frequency and determinants of BTE according to their location and severity in a retrospective analysis of the German ECMO COVID-19 registry. Logistic regression was applied to identify factors influencing ICU survival as well as variables associated with risks of BTE. In total, 708 of 945 patients (75%) suffered from BTE. Overall, 1348 events were registered, including 406 (30%) major bleeding and 258 (19%) major thromboembolic events. Most common major bleeding locations were intracranial (n=133, 10%) and pulmonary bleeding (n=116, 9%). In-ICU survival was 35%, 46% without BTE and 22% with major bleeding (p<0.05). In summary, major bleeding was a core outcome-determinant of COVID-19 ECMO mortality with intracranial major bleeding as the most devastating complication (OR: 5.3; CI: 2.9-9.9; p<0.001). Neither major thromboembolism nor minor BTE impacted ICU-mortality. Potentially modifiable factors associated with major bleeding included prolonged duration of ECMO >14 days (OR: 2.9; CI 1.8-4.7; p<0.001) and platelet counts <100.000/µL ≥72h (OR: 2.0; CI 1.1-3.6; p=0.018). Hence, prevention, early recognition and treatment of major bleedings are key to increase the survival of COVID-19 ECMO. In this regard, our data indicate that the implementation of early weaning strategies to minimize duration of ECMO therapy and prevention of prolonged thrombocytopenia with platelet counts <100.000/µl ≥72h could decrease the risk of devastating bleeds and could ameliorate survival.