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

Abstract

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in 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 SOFA score of 12 (8-16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1+2, thrombin-antithrombin, D-Dimers and PAI-1 were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation and fibrinolysis shut-down 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 non-fatal 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.

Characteristics and prognosis of bloodstream infection in patients with COVID-19 admitted in the ICU: an ancillary study of the COVID-ICU study

“…The following outcomes were also recorded: occurrence of thrombosis [ 19 ], duration of MV, vital status at ICU and hospital discharge and 28, 60 and 90 days after ICU admission.…”

D-dimer levels in non-COVID-19 ARDS and COVID-19 ARDS patients: A systematic review with meta-analysis

“…Studies included in the present manuscript were conducted in 6 countries (USA, UK, Germany, France, Italy, China). Most studies (n = 12) were retrospective [ 12 – 17 , 20 – 24 , 26 ], and the only 3 prospective studies included historical cohorts of non-COVID-19 ARDS patients [ 18 , 19 , 25 ]. In total, data from 2,828 patients were included in our meta-analysis, with 1,404 (49.6%) having non-COVID-19 ARDS and 1,424 (50.4%) COVID-19 ARDS ( Fig 2 ).…”

“…The non-COVID-19 ARDS patients had statistically lower fibrinogen levels (mean 454 mg/dl vs. 653 mg/dl) [ 12 – 15 , 18 – 21 , 25 , 26 ] when compared to COVID-19 ARDS patients resulting in a MD of -173 mg/dl (95% CI: -232.48 to -113.63) p<0.001 (S3 Fig in S1 File ). In contrast, CRP levels [ 13 – 15 , 18 , 20 – 23 ] (MD -1.07 mg/dl [95% CI: -5.08 to 2.95, p = 0.60]) and PaO2/FiO2 ratio [ 12 , 13 , 17 – 25 ] (MD -2.75 mmHg [95% CI: -10.15 to 4.65, p = 0.47]) were similar between groups (S2 and S4 Figs in S1 File ).…”

Viscoelastic Testing in the Management of Adult Patients on Mechanical Circulatory Support Devices with Focus on Extracorporeal Membrane Oxygenation

“…The hypercoagulable state is associated with increased fibrinogen levels, increased factor VIII activity, increased circulating von Willebrand factor (VWF) levels, and reduced fibrinolytic responses. 14 15 One small study that compared 20 patients with COVID-19-related ARDS and 10 patients with non-COVID-19-related ARDS described the interaction of the altered coagulation status of COVID-19 patients with the coagulation-altering effects of V-V ECMO. Baseline levels of D-dimer, and plasminogen activator inhibitor-1 (PAI-1), were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that fibrinolysis shutdown occurs in all ARDS patients before ECMO implantation.…”

“…Exposure to ECMO resulted in greater increases in thrombin generation (prothrombin F1 þ 2 levels) and fibrin formation, and greater decreases in platelet counts and fibrinogen levels in COVID-19 patients. 15 Currently, ELSO's interim anticoagulation guidelines recommend targeting anticoagulation levels at the higher end of normal ECMO parameters for COVID-19 patients which may contribute to the greater disruptions in hemostasis. 16 Additional monitoring of the coagulation status for COVID-19 patients on ECMO may be required to optimize anticoagulation therapy for each patient.…”