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

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.