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

• Type of Material: Article
• Authors: Cheryl Maier, Emory University; Tania Sarker, Emory University; Roman Sniecinski, Emory University; Fania Szlam, Emory University
• Language: English
• Date: 2021-04-07
• Publisher: Springer
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.
• Final Published Version (URL): http://dx.doi.org/10.1007/s11239-021-02438-y
• Title of Journal or Parent Work: Journal of Thrombosis and Thrombolysis
• Volume: 52
• Issue: 3
• Start Page: 766
• End Page: 771
• Grant/Funding Information: Research reported in this publication was supported in part by COVID Catalyst-I-3 Funds from the Woodruff Health Sciences Center and Emory School of Medicine and made possible through a grant from the O. Wayne Rollins Foundation, and through the Georgia CTSA NIH award (Grant No. UL1-TR002378).; CLM is also supported by NIH/NHLBI K99 HL150626-01.
• Keywords: Tissue plasminogen activator; Science & Technology; Cardiac & Cardiovascular Systems; Cardiovascular System & Cardiology; COVID-19; Peripheral Vascular Disease; Thromboelastography; Hematology; Fibrinolysis; Pulmonary embolism; Life Sciences & Biomedicine; Injury; Severe acute respiratory syndrome coronavirus 2
• Research Categories: Health Sciences, Pathology; Health Sciences, Medicine and Surgery; Health Sciences, Public Health

Abstract

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.