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

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.