Hypercoagulopathy, acquired coagulation disorders and anticoagulation before, during and after extracorporeal membrane oxygenation in COVID-19: a case series

Abstract

Background: Thromboembolism and bleeding contribute to Coronavirus disease 2019 (COVID-19)’s morbidity and mortality and are also frequent complications of venovenous extracorporeal membrane oxygenation (vvECMO). As the interaction of the underlying pathologies caused by vvECMO in COVID-19 is barely understood, we designed this study to better differentiate coagulation disorders in COVID-19 patients before, during and after vvECMO-support. Methods: Observational case series, six consecutive patients with Coronavirus acute respiratory distress syndrome supported with vvECMO treated in the anaesthesiologic ICU in a third level University ECMO-centre. We measured routine coagulation parameters and assessed coagulation factors. We also conducted advanced von Willebrand factor (VWF) multimer analysis, platelet aggregometry and immunological screening. Results: We identified various phases of coagulation disorders: Initially, intensely activated coagulation with highly increased VWF and factor VIII activity in acute COVID-19, then severe acquired von Willebrand syndrome and platelet dysfunction during vvECMO leading to spontaneous bleeding and finally, hypercoagulopathy after vvECMO explantation. Five of six patients developed immunological abnormalities enhancing coagulation. Conclusions: Coronavirus-induced coagulopathy and bleeding disorders during vvECMO cannot be discriminated via ‘routine’ coagulation tests. Precise and specific analyses followed by the appropriate treatment of coagulation disorders may help us develop tailored therapeutic concepts to better manage the phases described above.

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

“…The most common comorbidities were obesity (50%) and hypertension (20%). The median SAPS-II and SOFA scores were 54 (43-68) and 12 (8)(9)(10)(11)(12)(13)(14)(15)(16), respectively. The SOFA score tended to be higher in the COVID-19 group (12 [8.5-15.8] vs. 9.5 [7.0-17.2] in the non-COVID-19 group).…”

“…29 However, the rate of severe bleeding, including intracranial hemorrhage, and fatal bleeding on ECMO was particularly high in these studies. The hemostatic changes induced by ECMO support in COVID-19 patients have been yet poorly documented [15][16][17][18][19]30,31 and the optimal anticoagulation scheme remains unknown. The present study aimed to fill this knowledge gap by comprehensively describing the kinetics of coagulation and fibrinolysis markers during vv-ECMO support and their potential contribution to outcomes.…”

“…From October 22, 2019 (8)(9)(10)(11)(12)(13)(14)(15)(16), respectively. The SOFA score tended to be higher in the COVID-19 group [12 (8.5-15.8) versus 9.5 (7.0-17.2) in the non-COVID-19 group).…”

“…Positive end-expiratory pressure, cm of water Plateau pressure, cm of water Compliance, ml/cm of water 12 [10][11][12][13][14][15] 30 [28][29][30][31][32][33][34] 20.3 [15.3-30.3] 12 [7][8][9][10][11][12] 29 [19][20][21][22][23][24][25][26][27][28][29][30] 22.5 [21.2-32.9] 14 [10][11][12][13][14][15] 30 [28][29][30][31][32][33][34]…”

“…12,13 Some authors suggested that these bleeding events might result from worsening COVID-19-associated coagulopathy during ECMO support, further leading to disseminated intravascular coagulation, enhanced fibrinolysis or acquired von Willebrand syndrome, or from heparin overdose. 14 However, data on the kinetics of coagulation and fibrinolysis markers over the course of vv-ECMO in COVID-19 patients which might support this hypothesis are scarce [15][16][17][18][19] and direct comparisons with non-COVID-19 patients are lacking.…”