Assessing endothelial activation and risk of bleeding in patients receiving VV-ECMO supportive therapy for COVID-19 using non-standard laboratory assays

ABSTRACT

Background: Critically ill patients infected with the SARS-CoV- 2 virus are known to have a coagulopathy with a risk of thrombosis due to endothelial activation and systemic inflammation. Veno-venous extracorporeal membrane oxygenation (VV ECMO) is recommended by the World Health Organisation (WHO) as a supportive therapy for patients with severe COVID-19 infection when conventional ICU methods have proven ineffective. VV ECMO comes with haematological complications, including loss of high molecular weight von Willebrand factor multimers, consumption of clotting factors and premature activation of platelets. Laboratory methods to characterise haemostasis in these patients are required and may be clinically useful in predicting clinical outcome. Aim(s) Can non-standard methods provide clinically meaningful results in COVID-19 positive patients supported by VV ECMO? Methods: Tissue plasminogen activator and von Willebrand factor were quantified via Abcam SimpleStep ELISA in VV ECMO supported Covid-19 patients and normal controls. Fibrinogen antigen concentration was quantified via Liaphen Fibrinogen Antigen assay in VV ECMO supported Covid-19 patients and normal controls. VW Select ristocetin cofactor assay was used to assess von Willebrand Factor activity in VV ECMO supported COVID-19 patients. Result(s) Tissue plasminogen activator and von Willebrand factor concentrations are significantly increased in COVID-19 patients supported by VV ECMO compared to healthy controls, which reflects endothelial damage displayed in critically unwell COVID patients. Fibrinogen levels were not significantly different between the two patient groups. The VW Select ristocetin cofactor assay detected patients with low vWF activity that would have otherwise been overlooked by standard methods. Conclusion(s) Non-conventional laboratory methods can be used to represent the extent of endothelial damage and risk of bleeding in patients who are COVID-19 positive and anticoagulated on VV ECMO support. The assays help to characterise pathology of COVID-19 used in conjunction with standard tests by providing clinically relevant results. (Figure Presented).