Cargando…

COVID-19 patient plasma demonstrates resistance to tPA-induced fibrinolysis as measured by thromboelastography

Patients critically ill with COVID-19 are at risk for thrombotic events despite prophylactic anticoagulation. Impaired fibrinolysis has been proposed as an underlying mechanism. Our objective was to determine if fibrinolysis stimulated by tissue plasminogen activator (tPA) differed between COVID pat...

Descripción completa

Detalles Bibliográficos
Autores principales: Maier, Cheryl L., Sarker, Tania, Szlam, Fania, Sniecinski, Roman M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026096/
https://www.ncbi.nlm.nih.gov/pubmed/33829396
http://dx.doi.org/10.1007/s11239-021-02438-y
_version_ 1783675612338061312
author Maier, Cheryl L.
Sarker, Tania
Szlam, Fania
Sniecinski, Roman M.
author_facet Maier, Cheryl L.
Sarker, Tania
Szlam, Fania
Sniecinski, Roman M.
author_sort Maier, Cheryl L.
collection PubMed
description Patients critically ill with COVID-19 are at risk for thrombotic events despite prophylactic anticoagulation. Impaired fibrinolysis has been proposed as an underlying mechanism. Our objective was to determine if fibrinolysis stimulated by tissue plasminogen activator (tPA) differed between COVID patients and controls. Plasma from 14 COVID patients on prophylactic heparin therapy was obtained and compared with heparinized plasma from 14 different healthy donors to act as controls. Kaolin activated thromboelastography with heparinase was utilized to obtain baseline measurements and then repeated with the addition of 4 nM tPA. Baseline fibrinogen levels were higher in COVID plasma as measured by maximum clot amplitude (43.6 ± 6.9 mm vs. 23.2 ± 5.5 mm, p < 0.0001) and Clauss assay (595 ± 135 mg/dL vs. 278 ± 44 mg/dL, p < 0.0001). With the addition of tPA, fibrinolysis at 30 min after MA (LY30%) was lower (37.9 ± 16.5% vs. 58.9 ± 18.3%, p = 0.0035) and time to 50% lysis was longer (48.8 ± 16.3 vs. 30.5 ± 15.4 min, p = 0.0053) in the COVID-19 samples. Clotting times and rate of fibrin polymerization (‘R’ or ‘α’ parameters) were largely the same in both groups. Clot from COVID patients contains a higher fibrin content compared to standard controls and shows resistance to fibrinolysis induced by tPA. These findings suggest the clinical efficacy of thrombolytics may be reduced in COVID-19 patients.
format Online
Article
Text
id pubmed-8026096
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Springer US
record_format MEDLINE/PubMed
spelling pubmed-80260962021-04-08 COVID-19 patient plasma demonstrates resistance to tPA-induced fibrinolysis as measured by thromboelastography Maier, Cheryl L. Sarker, Tania Szlam, Fania Sniecinski, Roman M. J Thromb Thrombolysis Article Patients critically ill with COVID-19 are at risk for thrombotic events despite prophylactic anticoagulation. Impaired fibrinolysis has been proposed as an underlying mechanism. Our objective was to determine if fibrinolysis stimulated by tissue plasminogen activator (tPA) differed between COVID patients and controls. Plasma from 14 COVID patients on prophylactic heparin therapy was obtained and compared with heparinized plasma from 14 different healthy donors to act as controls. Kaolin activated thromboelastography with heparinase was utilized to obtain baseline measurements and then repeated with the addition of 4 nM tPA. Baseline fibrinogen levels were higher in COVID plasma as measured by maximum clot amplitude (43.6 ± 6.9 mm vs. 23.2 ± 5.5 mm, p < 0.0001) and Clauss assay (595 ± 135 mg/dL vs. 278 ± 44 mg/dL, p < 0.0001). With the addition of tPA, fibrinolysis at 30 min after MA (LY30%) was lower (37.9 ± 16.5% vs. 58.9 ± 18.3%, p = 0.0035) and time to 50% lysis was longer (48.8 ± 16.3 vs. 30.5 ± 15.4 min, p = 0.0053) in the COVID-19 samples. Clotting times and rate of fibrin polymerization (‘R’ or ‘α’ parameters) were largely the same in both groups. Clot from COVID patients contains a higher fibrin content compared to standard controls and shows resistance to fibrinolysis induced by tPA. These findings suggest the clinical efficacy of thrombolytics may be reduced in COVID-19 patients. Springer US 2021-04-07 2021 /pmc/articles/PMC8026096/ /pubmed/33829396 http://dx.doi.org/10.1007/s11239-021-02438-y Text en © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Maier, Cheryl L.
Sarker, Tania
Szlam, Fania
Sniecinski, Roman M.
COVID-19 patient plasma demonstrates resistance to tPA-induced fibrinolysis as measured by thromboelastography
title COVID-19 patient plasma demonstrates resistance to tPA-induced fibrinolysis as measured by thromboelastography
title_full COVID-19 patient plasma demonstrates resistance to tPA-induced fibrinolysis as measured by thromboelastography
title_fullStr COVID-19 patient plasma demonstrates resistance to tPA-induced fibrinolysis as measured by thromboelastography
title_full_unstemmed COVID-19 patient plasma demonstrates resistance to tPA-induced fibrinolysis as measured by thromboelastography
title_short COVID-19 patient plasma demonstrates resistance to tPA-induced fibrinolysis as measured by thromboelastography
title_sort covid-19 patient plasma demonstrates resistance to tpa-induced fibrinolysis as measured by thromboelastography
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026096/
https://www.ncbi.nlm.nih.gov/pubmed/33829396
http://dx.doi.org/10.1007/s11239-021-02438-y
work_keys_str_mv AT maiercheryll covid19patientplasmademonstratesresistancetotpainducedfibrinolysisasmeasuredbythromboelastography
AT sarkertania covid19patientplasmademonstratesresistancetotpainducedfibrinolysisasmeasuredbythromboelastography
AT szlamfania covid19patientplasmademonstratesresistancetotpainducedfibrinolysisasmeasuredbythromboelastography
AT sniecinskiromanm covid19patientplasmademonstratesresistancetotpainducedfibrinolysisasmeasuredbythromboelastography