Reduced anticoagulation strategy is associated with a lower incidence of intracerebral hemorrhage in COVID-19 patients on extracorporeal membrane oxygenation

Daniel A Hofmaenner; David Furfaro; Lennart C Wild; Pedro David Wendel-Garcia; Elias Baedorf Kassis; Ameeka Pannu; Tobias Welte; Rolf Erlebach; Klaus Stahl; Edward Wilson Grandin; Christian Putensen; Reto A Schuepbach; Shahzad Shaefi; Sascha David; Benjamin Seeliger; Christian Bode; BonHanZA study group

doi:10.1186/s40635-023-00525-3

Reduced anticoagulation strategy is associated with a lower incidence of intracerebral hemorrhage in COVID-19 patients on extracorporeal membrane oxygenation

Intensive Care Med Exp. 2023 Jun 12;11(1):38. doi: 10.1186/s40635-023-00525-3.

Authors

Daniel A Hofmaenner^#¹, David Furfaro^#², Lennart C Wild^#³, Pedro David Wendel-Garcia¹, Elias Baedorf Kassis², Ameeka Pannu⁴, Tobias Welte⁵, Rolf Erlebach¹, Klaus Stahl⁶, Edward Wilson Grandin⁷, Christian Putensen³, Reto A Schuepbach¹, Shahzad Shaefi⁴, Sascha David⁸, Benjamin Seeliger^#⁵, Christian Bode^#³; BonHanZA study group

Affiliations

¹ Institute of Intensive Care Medicine, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
² Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
³ Department of Anesthesia and Intensive Care Medicine, University Hospital Bonn, Bonn, Germany.
⁴ Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁵ Department of Respiratory Medicine, Hannover Medical School and Member of the German Centre for Lung Research, Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.
⁶ Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
⁷ Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.
⁸ Institute of Intensive Care Medicine, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland. sascha.david@usz.ch.

^# Contributed equally.

Abstract

Background: Optimal anticoagulation strategies for COVID-19 patients with the acute respiratory distress syndrome (ARDS) on venovenous extracorporeal membrane oxygenation (VV ECMO) remain uncertain. A higher incidence of intracerebral hemorrhage (ICH) during VV ECMO support compared to non-COVID-19 viral ARDS patients has been reported, with increased bleeding rates in COVID-19 attributed to both intensified anticoagulation and a disease-specific endotheliopathy. We hypothesized that lower intensity of anticoagulation during VV ECMO would be associated with a lower risk of ICH. In a retrospective, multicenter study from three academic tertiary intensive care units, we included patients with confirmed COVID-19 ARDS requiring VV ECMO support from March 2020 to January 2022. Patients were grouped by anticoagulation exposure into higher intensity, targeting anti-factor Xa activity (anti-Xa) of 0.3-0.4 U/mL, versus lower intensity, targeting anti-Xa 0.15-0.3 U/mL, cohorts. Mean daily doses of unfractionated heparin (UFH) per kg bodyweight and effectively measured daily anti-factor Xa activities were compared between the groups over the first 7 days on ECMO support. The primary outcome was the rate of ICH during VV ECMO support.

Results: 141 critically ill COVID-19 patients were included in the study. Patients with lower anticoagulation targets had consistently lower anti-Xa activity values over the first 7 ECMO days (p < 0.001). ICH incidence was lower in patients in the lower anti-Xa group: 4 (8%) vs 32 (34%) events. Accounting for death as a competing event, the adjusted subhazard ratio for the occurrence of ICH was 0.295 (97.5% CI 0.1-0.9, p = 0.044) for the lower anti-Xa compared to the higher anti-Xa group. 90-day ICU survival was higher in patients in the lower anti-Xa group, and ICH was the strongest risk factor associated with mortality (odds ratio [OR] 6.8 [CI 2.1-22.1], p = 0.001).

Conclusions: For COVID-19 patients on VV ECMO support anticoagulated with heparin, a lower anticoagulation target was associated with a significant reduction in ICH incidence and increased survival.

Keywords: Acute respiratory distress syndrome; Anticoagulants; Bleeding; COVID-19; Endothelium; Extracorporeal membrane oxygenation; Hemorrhage; Vascular.