Coagulation biomarkers and coronavirus disease 2019 phenotyping: a prospective cohort study

Emily Corneo; Rafael Garbelotto; Gabriele Prestes; Carolina Saibro Girardi; Lucas Santos; Jose Claudio Fonseca Moreira; Daniel Pens Gelain; Glauco A Westphal; Emil Kupek; Roger Walz; Cristiane Ritter; Felipe Dal-Pizzol

doi:10.1186/s12959-023-00524-0

Coagulation biomarkers and coronavirus disease 2019 phenotyping: a prospective cohort study

Thromb J. 2023 Jul 28;21(1):80. doi: 10.1186/s12959-023-00524-0.

Authors

Affiliations

¹ Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Santa Catarina, Av. Universitária, Criciúma, 1105, Brazil.
² Intensive Care Unit, Hospital São José, Criciúma, SC, Brazil.
³ Departamento de Bioquímica, Centro de Estudos Em Estresse Oxidativo, Instituto de Ciências Básicas da Saúde, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil.
⁴ Centro Hospitalar Unimed, Joinville, SC, Brazil.
⁵ Public Health Department, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
⁶ Center for Applied Neuroscience (CeNAp), Department of Clinical Medicine, University Hospital - Federal University of Santa Catarina, Florianópolis, SC, Brazil.
⁷ Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Santa Catarina, Av. Universitária, Criciúma, 1105, Brazil. piz@unesc.net.
⁸ Intensive Care Unit, Hospital São José, Criciúma, SC, Brazil. piz@unesc.net.
⁹ Clinical Research Center, Hospital São José, Criciúma, SC, Brazil. piz@unesc.net.

Abstract

Background: Because severe acute respiratory syndrome coronarivus 2 (SARS-CoV-2) leads to severe conditions and thrombus formation, evaluation of the coagulation markers is important in determining the prognosis and phenotyping of patients with COVID-19.

Methods: In a prospective study that included 213 COVID-19 patients admitted to the intensive care unit (ICU) the levels of antithrombin, C-reactive protein (CRP); factors XI, XII, XIII; prothrombin and D-dimer were measured. Spearman's correlation coefficient was used to assess the pairwise correlations between the biomarkers. Hierarchical and non-hierarchical cluster analysis was performed using the levels of biomarkers to identify patients´ phenotypes. Multivariate binary regression was used to determine the association of the patient´s outcome with clinical variables and biomarker levels.

Results: The levels of factors XI and XIII were significantly higher in patients with less severe COVID-19, while factor XIII and antithrombin levels were significantly associated with mortality. These coagulation biomarkers were associated with the in-hospital survival of COVID-19 patients over and above the core clinical factors on admission. Hierarchical cluster analysis showed a cluster between factor XIII and antithrombin, and this hierarchical cluster was extended to CRP in the next step. Furthermore, a non-hierarchical K-means cluster analysis was performed, and two phenotypes were identified based on the CRP and antithrombin levels independently of clinical variables and were associated with mortality.

Conclusion: Coagulation biomarkers were associated with in-hospital survival of COVID-19 patients. Lower levels of factors XI, XII and XIII and prothrombin were associated with disease severity, while higher levels of both CRP and antithrombin clustered with worse prognosis. These results suggest the role of coagulation abnormalities in the development of COVID-19 and open the perspective of identifying subgroups of patients who would benefit more from interventions focused on regulating coagulation.

Keywords: COVID-19; Cluster phenotyping; Coagulation; Coagulation factors; Prognostication.