TY - JOUR
T1 - Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients
AU - Goswami, Julie
AU - MacArthur, Taleen A.
AU - Sridharan, Meera
AU - Tange, Julie
AU - Kirmse, Andrew J.
AU - Lundell, Kaitlin A.
AU - Chen, Dong
AU - Auton, Matthew T.
AU - Chon, Tony Y
AU - Hurt, Ryan T.
AU - Salonen, Bradley R.
AU - Ganesh, Ravindra
AU - Erben, Young M.
AU - Marquez, Christopher P.
AU - Dong, Jing Fei
AU - Kozar, Rosemary A.
AU - Heller, Stephanie F.
AU - Loomis, Erica A.
AU - Johnstone, Andrea L.
AU - Bailey, Kent R.
AU - Spears, Grant M.
AU - Park, Myung (Michelle) S
N1 - Funding Information:
This project was supported by T32 AG049672 from the National Institute of Aging (NIA) and Robert and Arlene Kogod Center for Aging, Mayo Clinic (JG), R38HL150086 Stimulating Access to Research in Residency (TAM) from the National Heart, Lung, and Blood Institute (NHLBI) , HL146508 from the NHLBI (MA), UM1 HL120877-06 (MSP) by the Trans-Agency Consortium for Trauma-Induced Coagulopathy (TACTIC), EpiCypher (ALJ) is supported by the NIH under award numbers R43AI134162 from the National Institute of Allergy and Infectious Diseases (NIAID) , R43GM131560 from the National Institute of General Medical Sciences (NIGMS) , and R44AI134162 ( NIAID ). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2021 The Authors
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - COVID-19
KW - Extracellular traps
KW - Thrombin
KW - Von Willebrand factor
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U2 - 10.1016/j.tru.2021.100090
DO - 10.1016/j.tru.2021.100090
M3 - Article
AN - SCOPUS:85126093164
VL - 5
JO - Thrombosis Update
JF - Thrombosis Update
SN - 2666-5727
M1 - 100090
ER -