Abstract Number: PB0605
Meeting: ISTH 2022 Congress
Background: COVID-19 disease arises from infection with severe acute respiratory cornonavirus-2 (SARS-CoV-2). Severe disease is associated with a coagulopathy characterised by elevated D-dimer levels, fibrin deposition in the lung, and a thrombotic incidence of approximately 30%, indicating catastrophic derailment of the haemostatic system.
Aims: To investigate whether SARS-CoV-2-induced coagulopathy arises due to an imbalance in the fibrinolysis.
Methods: Citrated plasma was collected from 139 patients presenting with symptomatic COVID-19, 24 patients with non-COVID-19 respiratory infection and 30 healthy controls in a dual-centre study. Fibrinolytic biomarkers were evaluated including plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), plasminogen, vitronectin and thrombin activatable fibrinolysis inhibitor (TAFI). Furthermore, diagnostic biomarkers including, fibrinogen, C-reactive protein (CRP), D-dimer and inflammatory cytokines were quantified. Clot lysis was evaluated using turbidity assays, plasma clot structure visualised by confocal microscopy and plasmin generation quantified by chromogenic substrate.
Results: PAI-1 antigen, activity, and the cofactor for this serpin, vitronectin, were significantly elevated in patients with COVID-19 compared to healthy controls and non-COVID-19 respiratory infection. Patients with COVID-19 exhibit attenuated plasmin generation compared to healthy volunteers despite significant elevation in tPA. PAI-1 correlated with inflammatory cytokines (IL-1β, IL-8 and TNF-α). In line with this acute phase proteins, fibrinogen and CRP were high in patients with COVID-19 but only CRP was increased compared to non-COVID-19 respiratory infections. Levels of PAI-1 and vitronectin were associated with escalating oxygen support and a corresponding decrease in plasminogen. Importantly, patients with COVID-19 disease exhibit resistance to fibrinolytic degradation by Actilyse®, however, this could be overcome by the PAI-1 resistant form of tPA, Metalyse®.
Conclusion(s): We reveal that COVID-19 disease promotes a hypofibrinolytic state due to elevated PAI-1 and its stabilizing cofactor vitronectin. PAI-1 correlates with inflammatory cytokines and disease severity thereby highlighting its potential prognostic power in the development of severe COVID-19 disease.
To cite this abstract in AMA style:Simpson M, Whyte C, Morrow G, Wallace C, Mentzer A, Knight J, Shapiro S, Curry N, Bagot C, Watson H, Cooper J, Mutch N. COVID-19 disease is associated with a hypofibrinolytic state driven by elevated plasminogen activator inhibitor-1 and its cofactor vitronectin [abstract]. https://abstracts.isth.org/abstract/covid-19-disease-is-associated-with-a-hypofibrinolytic-state-driven-by-elevated-plasminogen-activator-inhibitor-1-and-its-cofactor-vitronectin/. Accessed September 29, 2023.
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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/covid-19-disease-is-associated-with-a-hypofibrinolytic-state-driven-by-elevated-plasminogen-activator-inhibitor-1-and-its-cofactor-vitronectin/