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Thromb Haemost 2021; 121(08): 1031-1042
DOI: 10.1055/a-1529-2257
Coagulation and Fibrinolysis

Extracorporeal Membrane Oxygenation Induces Early Alterations in Coagulation and Fibrinolysis Profiles in COVID-19 Patients with Acute Respiratory Distress Syndrome

Guillaume Hékimian
1   Medical Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
2   Sorbonne Université, INSERM UMRS_1166, Institute of Cardiometabolism And Nutrition, Paris, France
,
Paul Masi
1   Medical Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
,
Manon Lejeune
2   Sorbonne Université, INSERM UMRS_1166, Institute of Cardiometabolism And Nutrition, Paris, France
3   Department of Hematology, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
,
Guillaume Lebreton
2   Sorbonne Université, INSERM UMRS_1166, Institute of Cardiometabolism And Nutrition, Paris, France
4   Department of Cardiothoracic Surgery, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
,
Juliette Chommeloux
1   Medical Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
,
Cyrielle Desnos
1   Medical Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
,
Marc Pineton De Chambrun
1   Medical Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
,
Isabelle Martin-Toutain
3   Department of Hematology, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
,
Ania Nieszkowska
1   Medical Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
,
Nicolas Bréchot
1   Medical Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
,
Matthieu Schmidt
1   Medical Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
2   Sorbonne Université, INSERM UMRS_1166, Institute of Cardiometabolism And Nutrition, Paris, France
,
Pascal Leprince
2   Sorbonne Université, INSERM UMRS_1166, Institute of Cardiometabolism And Nutrition, Paris, France
4   Department of Cardiothoracic Surgery, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
,
Charles-Edouard Luyt
1   Medical Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
2   Sorbonne Université, INSERM UMRS_1166, Institute of Cardiometabolism And Nutrition, Paris, France
,
Alain Combes
1   Medical Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
2   Sorbonne Université, INSERM UMRS_1166, Institute of Cardiometabolism And Nutrition, Paris, France
,
Corinne Frere 
2   Sorbonne Université, INSERM UMRS_1166, Institute of Cardiometabolism And Nutrition, Paris, France
3   Department of Hematology, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France
› Author Affiliations Funding This work was sponsored by Assistance Publique-Hôpitaux de Paris. QPlus® cartridges were provided by Stago BioCare free of charge.
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Abstract

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in coronavirus-19 (COVID-19) patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7, and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35–56) years, with a median body mass index of 30 (27–35) kg/m2, and a Sepsis-related Organ Failure Assessment score of 12 (8–16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1 + 2, thrombin–antithrombin, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation, and fibrinolysis shutdown occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1 + 2, p < 0.01) and fibrin formation markers (fibrin monomers, p < 0.001) significantly increased, further resulting in significant decreases in platelet count (p < 0.0001) and fibrinogen level (p < 0.001). PAI-1 levels significantly decreased from baseline to day 7 (p < 0.0001) in all ARDS patients. These changes were more marked in COVID-19 patients, resulting in 14 nonfatal and 3 fatal bleeding. Additional studies are warranted to determine whether monitoring of thrombin generation and fibrinolysis markers might help to early predict bleeding complications in COVID-19 patients supported by ECMO.

Keywords

extracorporeal membrane oxygenation - COVID-19 - coagulation - fibrinolysis - bleeding

Supplementary Material



Publication History

Received: 13 April 2021

Accepted: 14 June 2021

Accepted Manuscript online:
15 June 2021

Article published online:
11 July 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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