Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients

Julie Goswami; Taleen A MacArthur; Meera Sridharan; Julie Tange; Andrew J Kirmse; Kaitlin A Lundell; Dong Chen; Matthew T Auton; Tony Y Chon; Ryan T Hurt; Bradley R Salonen; Ravindra Ganesh; Young M Erben; Christopher P Marquez; Jing-Fei Dong; Rosemary A Kozar; Stephanie F Heller; Erica A Loomis; Andrea L Johnstone; Kent R Bailey; Grant M Spears; Myung S Park

doi:10.1016/j.tru.2021.100090

Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients

Thromb Update. 2021 Dec:5:100090. doi: 10.1016/j.tru.2021.100090. Epub 2021 Nov 19.

Authors

Julie Goswami¹, Taleen A MacArthur¹, Meera Sridharan², Julie Tange², Andrew J Kirmse¹, Kaitlin A Lundell¹, Dong Chen³, Matthew T Auton⁴, Tony Y Chon⁵, Ryan T Hurt⁵, Bradley R Salonen⁵, Ravindra Ganesh⁵, Young M Erben⁶, Christopher P Marquez⁷, Jing-Fei Dong⁸, Rosemary A Kozar⁹, Stephanie F Heller¹, Erica A Loomis¹, Andrea L Johnstone¹⁰, Kent R Bailey¹¹, Grant M Spears¹¹, Myung S Park^{1

2}

Affiliations

¹ Trauma, Critical Care, and General Surgery, Department of Surgery, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA.
² Department of Hematology, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA.
³ Division of Hematopathology, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA.
⁴ Division of Biochemistry and Molecular Biology, Department of Hematology, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA.
⁵ Department of General Internal Medicine, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA.
⁶ Department of Vascular and Endovascular Surgery, Mayo Clinic, 4500 San Pablo Road S., Jacksonville, FL, 32224, USA.
⁷ Department of Laboratory Medicine and Pathology, Mayo Clinic, 4500 San Pablo Road S., Jacksonville, FL, 32224, USA.
⁸ Division of Hematology, University of Washington School of Medicine, Bloodworks Research Institute, 1551 Eastlake Avenue E, Seattle, WA, 98102, USA.
⁹ Shock Trauma Center, University of Maryland School of Medicine, 22 S Greene St, Baltimore, MD, 21201, USA.
¹⁰ EpiCypher Inc., Durham, NC, 27709, USA.
¹¹ Clinical Statistics and Biostatistics, Department of Health Sciences Research, Mayo Clinic, 200 1st St. SW, Rochester, MN, 55905, USA.

Abstract

Background: COVID-19-associated coagulopathy is incompletely understood.

Objectives: To characterize thrombin generation, Von Willebrand Factor (VWF), neutrophil extracellular traps (NETs), and their role in COVID-19 risk stratification in the emergency department (ED).

Patients/methods: Plasma samples from 67 ED COVID-19 patients were compared to 38 healthy volunteers (HVs). Thrombin generation (calibrated automated thrombogram, CAT) was expressed as lag time (LT, min), peak height (PH, min), and time to peak (ttPeak, min). Citrullinated nucleosomes and histones were quantified with ELISA, VWF antigen and activity (IU/dL) through latex immunoassay, Factor VIII (IU/dL) through one-stage optical clot detection, and VWF multimers with Western blot densitometry. Wilcoxon testing and multivariable logistic regression were performed. Results presented as median [Q1, Q3]; p < 0.05 significant.

Results: COVID-19 patients had longer LT (4.00 [3.26, 4.67]; 2.95 [2.67, 3.10], p < 0.001) and ttPeak (7.33 [6.33, 8.04]; 6.45 [6.00, 7.50], p = 0.004), greater VWF antigen (212 [158, 275]; 110 [91, 128], p < 0.001) and Factor VIII levels (148 [106, 190]; 106 [86, 129], p < 0.001), with decreased high molecular weight multimers (Normalized multimer ratio 0.807 [0.759, 0.869]; 0.891 [0.858, 0.966], p < 0.001), than HVs. COVID-19 patients requiring admission from the ED had longer LT and ttPeak with greater VWF antigen and Factor VIII levels than those not admitted. Two and three variable models of CAT parameters and VWF correlated with COVID-19 and admission status (C-statistics 0.677 to 0.922).

Conclusions: Thrombin generation kinetics and VWF levels, independent of NETs, may have a role in predicting admission need for COVID-19 patients.

Keywords: COVID-19; Extracellular traps; Thrombin; Von Willebrand factor.