Prognostic value of thrombin generation parameters in hospitalized COVID-19 patients

Abstract SARS-CoV-2 infection increases the risk of thrombosis by different mechanisms not fully characterized. Although still debated, an increase in D-dimer has been proposed as a first-line hemostasis test associated with thromboembolic risk and unfavorable prognosis. We aim to systematically and...

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Autores principales: María Eugenia de la Morena-Barrio, Carlos Bravo-Pérez, Antonia Miñano, Belén de la Morena-Barrio, María Piedad Fernandez-Perez, Enrique Bernal, José Miguel Gómez-Verdu, María Teresa Herranz, Vicente Vicente, Javier Corral, María Luisa Lozano
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:1da8638328ab40a2b372e68d84f6ad372021-12-02T14:37:46ZPrognostic value of thrombin generation parameters in hospitalized COVID-19 patients10.1038/s41598-021-85906-y2045-2322https://doaj.org/article/1da8638328ab40a2b372e68d84f6ad372021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85906-yhttps://doaj.org/toc/2045-2322Abstract SARS-CoV-2 infection increases the risk of thrombosis by different mechanisms not fully characterized. Although still debated, an increase in D-dimer has been proposed as a first-line hemostasis test associated with thromboembolic risk and unfavorable prognosis. We aim to systematically and comprehensively evaluate the association between thrombin generation parameters and the inflammatory and hypercoagulable state, as well as their prognostic value in COVID-19 patients. A total of 127 hospitalized patients with confirmed COVID-19, 24 hospitalized patients with SARS-CoV-2-negative pneumonia and 12 healthy subjects were included. Clinical characteristics, thrombin generation triggered by tissue factor with and without soluble thrombomodulin, and also by silica, as well as other biochemical parameters were assessed. Despite the frequent use of heparin, COVID-19 patients had similar thrombin generation to healthy controls. In COVID-19 patients, the thrombin generation lag-time positively correlated with markers of cell lysis (LDH), inflammation (CRP, IL-6) and coagulation (D-dimer), while the endogenous thrombin potential (ETP) inversely correlated with D-dimer and LDH, and positively correlated with fibrinogen levels. Patients with more prolonged lag-time and decreased ETP had higher peak ISTH-DIC scores, and had more severe disease (vascular events and death). The ROC curve and Kaplan Meier estimate indicated that the D-dimer/ETP ratio was associated with in-hospital mortality (HR 2.5; p = 0.006), and with the occurrence of major adverse events (composite end-point of vascular events and death) (HR 2.38; p = 0.004). The thrombin generation ETP and lag-time variables correlate with thromboinflammatory markers, and the D-dimer/ETP ratio can predict major adverse events in COVID-19.María Eugenia de la Morena-BarrioCarlos Bravo-PérezAntonia MiñanoBelén de la Morena-BarrioMaría Piedad Fernandez-PerezEnrique BernalJosé Miguel Gómez-VerduMaría Teresa HerranzVicente VicenteJavier CorralMaría Luisa LozanoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
María Eugenia de la Morena-Barrio
Carlos Bravo-Pérez
Antonia Miñano
Belén de la Morena-Barrio
María Piedad Fernandez-Perez
Enrique Bernal
José Miguel Gómez-Verdu
María Teresa Herranz
Vicente Vicente
Javier Corral
María Luisa Lozano
Prognostic value of thrombin generation parameters in hospitalized COVID-19 patients
description Abstract SARS-CoV-2 infection increases the risk of thrombosis by different mechanisms not fully characterized. Although still debated, an increase in D-dimer has been proposed as a first-line hemostasis test associated with thromboembolic risk and unfavorable prognosis. We aim to systematically and comprehensively evaluate the association between thrombin generation parameters and the inflammatory and hypercoagulable state, as well as their prognostic value in COVID-19 patients. A total of 127 hospitalized patients with confirmed COVID-19, 24 hospitalized patients with SARS-CoV-2-negative pneumonia and 12 healthy subjects were included. Clinical characteristics, thrombin generation triggered by tissue factor with and without soluble thrombomodulin, and also by silica, as well as other biochemical parameters were assessed. Despite the frequent use of heparin, COVID-19 patients had similar thrombin generation to healthy controls. In COVID-19 patients, the thrombin generation lag-time positively correlated with markers of cell lysis (LDH), inflammation (CRP, IL-6) and coagulation (D-dimer), while the endogenous thrombin potential (ETP) inversely correlated with D-dimer and LDH, and positively correlated with fibrinogen levels. Patients with more prolonged lag-time and decreased ETP had higher peak ISTH-DIC scores, and had more severe disease (vascular events and death). The ROC curve and Kaplan Meier estimate indicated that the D-dimer/ETP ratio was associated with in-hospital mortality (HR 2.5; p = 0.006), and with the occurrence of major adverse events (composite end-point of vascular events and death) (HR 2.38; p = 0.004). The thrombin generation ETP and lag-time variables correlate with thromboinflammatory markers, and the D-dimer/ETP ratio can predict major adverse events in COVID-19.
format article
author María Eugenia de la Morena-Barrio
Carlos Bravo-Pérez
Antonia Miñano
Belén de la Morena-Barrio
María Piedad Fernandez-Perez
Enrique Bernal
José Miguel Gómez-Verdu
María Teresa Herranz
Vicente Vicente
Javier Corral
María Luisa Lozano
author_facet María Eugenia de la Morena-Barrio
Carlos Bravo-Pérez
Antonia Miñano
Belén de la Morena-Barrio
María Piedad Fernandez-Perez
Enrique Bernal
José Miguel Gómez-Verdu
María Teresa Herranz
Vicente Vicente
Javier Corral
María Luisa Lozano
author_sort María Eugenia de la Morena-Barrio
title Prognostic value of thrombin generation parameters in hospitalized COVID-19 patients
title_short Prognostic value of thrombin generation parameters in hospitalized COVID-19 patients
title_full Prognostic value of thrombin generation parameters in hospitalized COVID-19 patients
title_fullStr Prognostic value of thrombin generation parameters in hospitalized COVID-19 patients
title_full_unstemmed Prognostic value of thrombin generation parameters in hospitalized COVID-19 patients
title_sort prognostic value of thrombin generation parameters in hospitalized covid-19 patients
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/1da8638328ab40a2b372e68d84f6ad37
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