Thrombin generation, viscoelastic coagulation profiles, and disease severity in critically Ill COVID-19 patients: a prospective observational study

Abstract

COVID-19-associated coagulopathy is characterized by complex alterations in haemostasis. While thrombin generation assays (TGA) provide a global assessment of coagulation potential, data on thrombin generation in critically ill COVID-19 patients, particularly those requiring extracorporeal membrane oxygenation (ECMO), remain limited. To describe thrombin generation, viscoelastic coagulation profiles, and contact pathway-related markers in critically ill COVID-19 patients and to explore their association with disease severity during the first week of intensive care treatment. In this prospective single-center observational study, 48 critically ill patients with COVID-19-associated acute respiratory distress syndrome were included. TGA parameters, rotational thromboelastometry (ROTEM), and contact pathway-related markers were assessed on days 1, 3, and 7 after ICU admission. Associations with disease severity were explored using the Sequential Organ Failure Assessment (SOFA) score. Analyses were exploratory and primarily descriptive. Endogenous thrombin potential (ETP) was inversely correlated with SOFA score on day 1 (r = − 0.43), day 3 (r = − 0.49), and day 7 (r = − 0.31). Peak thrombin showed similar inverse correlations on days 1 and 3. No significant differences in thrombin generation parameters were observed according to SIC status or SAC categories 24 h after ICU admission. ROTEM analyses demonstrated increased clot firmness together with elevated lysis indices and mildly prolonged EXTEM clotting times. Contact pathway-related markers, including factor XI, factor XII, and plasma kallikrein, were inversely associated with disease severity, while factor Xa activity decreased during the observation period. In this cohort of critically ill COVID-19 patients, thrombin generation parameters were inversely associated with disease severity, whereas no association was observed with SIC or SAC-defined coagulopathy. Viscoelastic testing demonstrated increased clot firmness and elevated lysis indices, while contact pathway-related markers decreased with increasing disease severity. These findings provide a descriptive characterization of coagulation abnormalities in critically ill COVID-19 patients and should be interpreted in the context of frequent ECMO support and systemic anticoagulation.