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

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...

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Autores principales: Hofmaenner, Daniel A., Furfaro, David, Wild, Lennart C., Wendel-Garcia, Pedro David, Baedorf Kassis, Elias, Pannu, Ameeka, Welte, Tobias, Erlebach, Rolf, Stahl, Klaus, Grandin, Edward Wilson, Putensen, Christian, Schuepbach, Reto A., Shaefi, Shahzad, David, Sascha, Seeliger, Benjamin, Bode, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10257972/
https://www.ncbi.nlm.nih.gov/pubmed/37302996
http://dx.doi.org/10.1186/s40635-023-00525-3
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author Hofmaenner, Daniel A.
Furfaro, David
Wild, Lennart C.
Wendel-Garcia, Pedro David
Baedorf Kassis, Elias
Pannu, Ameeka
Welte, Tobias
Erlebach, Rolf
Stahl, Klaus
Grandin, Edward Wilson
Putensen, Christian
Schuepbach, Reto A.
Shaefi, Shahzad
David, Sascha
Seeliger, Benjamin
Bode, Christian
author_facet Hofmaenner, Daniel A.
Furfaro, David
Wild, Lennart C.
Wendel-Garcia, Pedro David
Baedorf Kassis, Elias
Pannu, Ameeka
Welte, Tobias
Erlebach, Rolf
Stahl, Klaus
Grandin, Edward Wilson
Putensen, Christian
Schuepbach, Reto A.
Shaefi, Shahzad
David, Sascha
Seeliger, Benjamin
Bode, Christian
author_sort Hofmaenner, Daniel A.
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40635-023-00525-3.
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spelling pubmed-102579722023-06-12 Reduced anticoagulation strategy is associated with a lower incidence of intracerebral hemorrhage in COVID-19 patients on extracorporeal membrane oxygenation Hofmaenner, Daniel A. Furfaro, David Wild, Lennart C. Wendel-Garcia, Pedro David Baedorf Kassis, Elias Pannu, Ameeka Welte, Tobias Erlebach, Rolf Stahl, Klaus Grandin, Edward Wilson Putensen, Christian Schuepbach, Reto A. Shaefi, Shahzad David, Sascha Seeliger, Benjamin Bode, Christian Intensive Care Med Exp Research Articles 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40635-023-00525-3. Springer International Publishing 2023-06-12 /pmc/articles/PMC10257972/ /pubmed/37302996 http://dx.doi.org/10.1186/s40635-023-00525-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Hofmaenner, Daniel A.
Furfaro, David
Wild, Lennart C.
Wendel-Garcia, Pedro David
Baedorf Kassis, Elias
Pannu, Ameeka
Welte, Tobias
Erlebach, Rolf
Stahl, Klaus
Grandin, Edward Wilson
Putensen, Christian
Schuepbach, Reto A.
Shaefi, Shahzad
David, Sascha
Seeliger, Benjamin
Bode, Christian
Reduced anticoagulation strategy is associated with a lower incidence of intracerebral hemorrhage in COVID-19 patients on extracorporeal membrane oxygenation
title Reduced anticoagulation strategy is associated with a lower incidence of intracerebral hemorrhage in COVID-19 patients on extracorporeal membrane oxygenation
title_full Reduced anticoagulation strategy is associated with a lower incidence of intracerebral hemorrhage in COVID-19 patients on extracorporeal membrane oxygenation
title_fullStr Reduced anticoagulation strategy is associated with a lower incidence of intracerebral hemorrhage in COVID-19 patients on extracorporeal membrane oxygenation
title_full_unstemmed Reduced anticoagulation strategy is associated with a lower incidence of intracerebral hemorrhage in COVID-19 patients on extracorporeal membrane oxygenation
title_short Reduced anticoagulation strategy is associated with a lower incidence of intracerebral hemorrhage in COVID-19 patients on extracorporeal membrane oxygenation
title_sort reduced anticoagulation strategy is associated with a lower incidence of intracerebral hemorrhage in covid-19 patients on extracorporeal membrane oxygenation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10257972/
https://www.ncbi.nlm.nih.gov/pubmed/37302996
http://dx.doi.org/10.1186/s40635-023-00525-3
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