PB1373 - Time-dependent associations between COVID-19 disease severity, coagulation proteins, venous thromboembolism and all-cause mortality

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

MS

Mark J.R. Smeets

PhD Candidate
Department of Clinical Epidemiology, Leiden University Medical Center, The Netherlands
The Hague, Zuid-Holland, Netherlands

Co-Author(s)

RT

Roula Tsonaka

Assistant Professor
Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands
Cd

Cindy M.M. de Jong

PhD Candidate
Department of Internal Medicine, section Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
LB

Louise L.I. Burggraaf - van Delft

PhD Candidate
Department of Clinical Epidemiology, Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
AR

Anna H.E. Roukens

Infectious Diseases consultant, PhD
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
MA

M. Sesmu Arbous

Intensive Care consultant, PhD
Department of Intensive Care, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands
AR

Araci M.R. Rondon

Postdoctoral researcher
Einthoven Laboratory for Vascular and Regenerative Medicine, section Thrombosis and Hemostasis, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Leiden, Zuid-Holland, Netherlands
Henri Versteeg, PhD

Professor
Leiden University Medical Center
Leiden, Zuid-Holland, Netherlands
Suzanne C. Cannegieter

MD, PhD, prof
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Leiden, Zuid-Holland, Netherlands
Jeroen Eikenboom

MD, PhD, prof
Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands

Background: COVID-19 is a risk factor for VTE and mortality. Yet, due to their complexity, mechanistic relations between COVID-19 severity, alterations in coagulation protein levels, and the incidence of mortality and venous thromboembolism (VTE) are still unclear.

Aims: To obtain enhanced pathophysiological insights for VTE and mortality in patients admitted for COVID-19 by utilizing time-dependent analyses in an extensive longitudinal dataset.

Methods: For this cohort study, patients admitted with COVID-19 to the Leiden University Medical Center (LUMC) from April 2020 to March 2021 were included. Von Willebrand Factor (VWF), Factor VIII (FVIII), Tissue Factor (TF), Prothrombin Fragment 1+2 (Prothrombin F1+2), Thrombin-antithrombin complexes (TAT), and D-dimer were measured at multiple timepoints. Time-dependent disease severity was assessed using the severity of coronavirus disease assessment (SCODA) score. We longitudinally modelled progression of coagulation proteins over time – stratified by time-dependent disease severity – in linear mixed models, estimated VTE and mortality incidences using a multi-state approach (accounting for competing risks), and estimated adjusted hazard ratios for the time-dependent severity score and coagulation proteins with joint-models.

Written informed consent was obtained from all participants or close relatives and the LUMC Medical Ethics committee approved the study.

Results: Among 188 patients (75% male), levels of coagulation proteins varied over disease progression but were generally higher in more severe cases (figure). At 60 days post-COVID-19 onset, incidences of VTE, mortality, and mortality following VTE were 30% (95% Confidence Interval [CI] 24–37%), 14% (9–21%) and 14% (10–22%), respectively. Time-dependent disease severity, VWF, FVIII, and TF were positively associated with VTE/mortality, while the opposite was the case for TAT (table).

Conclusion(s): In these novel, time-dependent analyses, COVID-19 severity and coagulation protein levels were clearly associated with each other, as well as with the risk of VTE/mortality. These results deepen our pathophysiological understanding of VTE and mortality in COVID-19 patients.