The suboptimal fibrinolytic response in COVID-19 is dictated by high PAI-1.
J Thromb Haemost
; 20(10): 2394-2406, 2022 10.
Artigo
em Inglês
| MEDLINE | ID: covidwho-1916259
ABSTRACT
BACKGROUND:
Severe COVID-19 disease is associated with thrombotic complications and extensive fibrin deposition. This study investigates whether the hemostatic complications in COVID-19 disease arise due to dysregulation of the fibrinolytic system.METHODS:
This prospective study analyzed fibrinolytic profiles of 113 patients hospitalized with COVID-19 disease with 24 patients with non-COVID-19 respiratory infection and healthy controls. Antigens were quantified by Ella system or ELISA, clot lysis by turbidimetric assay, and plasminogen activator inhibitor-1 (PAI-1)/plasmin activity using chromogenic substrates. Clot structure was visualized by confocal microscopy.RESULTS:
PAI-1 and its cofactor, vitronectin, are significantly elevated in patients with COVID-19 disease compared with those with non-COVID-19 respiratory infection and healthy control groups. Thrombin activatable fibrinolysis inhibitor and tissue plasminogen activator were elevated in patients with COVID-19 disease relative to healthy controls. PAI-1 and tissue plasminogen activator (tPA) were associated with more severe COVID-19 disease severity. Clots formed from COVID-19 plasma demonstrate an altered fibrin network, with attenuated fiber length and increased branching. Functional studies reveal that plasmin generation and clot lysis were markedly attenuated in COVID-19 disease, while PAI-1 activity was elevated. Clot lysis time significantly correlated with PAI-1 levels. Stratification of COVID-19 samples according to PAI-1 levels reveals significantly faster lysis when using the PAI-1 resistant (tPA) variant, tenecteplase, over alteplase lysis.CONCLUSION:
This study shows that the suboptimal fibrinolytic response in COVID-19 disease is directly attributable to elevated levels of PAI-1, which attenuate plasmin generation. These data highlight the important prognostic potential of PAI-1 and the possibility of using pre-existing drugs, such as tenecteplase, to treat COVID-19 disease and potentially other respiratory diseases.Palavras-chave
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
MEDLINE
Assunto principal:
Trombose
/
Hemostáticos
/
Carboxipeptidase B2
/
Tratamento Farmacológico da COVID-19
Tipo de estudo:
Estudo de coorte
/
Estudo experimental
/
Estudo observacional
/
Estudo prognóstico
/
Ensaios controlados aleatorizados
Tópicos:
Variantes
Limite:
Humanos
Idioma:
Inglês
Revista:
J Thromb Haemost
Assunto da revista:
Hematologia
Ano de publicação:
2022
Tipo de documento:
Artigo
País de afiliação:
Jth.15806
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