Extracorporeal membrane oxygenation induces early alterations in coagulation and fibrinolysis profiles in COVID-19patients with acute respiratory distress syndrome

Background : Extracorporeal membrane oxygenation (ECMO) support induces complex hemostatic changes that have been yet poorly described, particularly in COVID-19 patients. Aims : To comprehensively analyze changes in coagulation and fibrinolysis profiles occurring during ECMO support in COVID-19 and non-COVID-19 patients with severe acute respiratory distress syndrome (ARDS). Methods : All consecutive patients with ARDS undergoing ECMO were eligible to participate in this prospective monocentric study. Clinical characteristics were recorded on admission. Blood was sampled before and then 24 h, 7 and 14 days after ECMO implantation for longitudinal measurement of coagulation and fibrinolysis markers. Clinical outcomes were prospectively assessed until discharge from the ICU or death. Results : We included 20 COVID-19 and 10 non-COVID-19 participants. The median age was 47 (35-56) years, with a median body mass index of 30 (27-35) kg/m, 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 groups, indicating that endothelial activation, endogenous thrombin generation and fibrinolysis shut-down occur in all ARDS patients before ECMO implantation. From baseline to day 7, platelet count ( P < 0.0001) and fibrinogen level ( P < 0.001) significantly decreased, resulting from increases in thrombin generation (prothrombin F1+2, P < 0.01) and fibrin formation (fibrin monomers, 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 3 fatal bleeding. Conclusions : ECMO circuit triggers early coagulation activation, resulting in significant fibrinogen and platelets consumption, with subsequent hypofibrinogenemia and thrombocytopenia, which may have contributed to the high prevalence of bleeding complications observed in COVID-19 ARDS patients rescued by ECMO. Additional studies are warranted to determine whether individualized anticoagulation might help to reduce bleeding complications during ECMO support. For now, daily monitoring of platelet count and fibrinogen should be part of ECMO management.