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 , Myung S. Park
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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.</p></div><div><h3>Results</h3><p>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).</p></div><div><h3>Conclusions</h3><p>Thrombin generation kinetics and VWF levels, independent of NETs, may have a role in predicting admission need for COVID-19 patients.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666572721000596/pdfft?md5=8fc84fabfceef10e1dc30defc7dd93c3&pid=1-s2.0-S2666572721000596-main.pdf","citationCount":"2","resultStr":"{\"title\":\"Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients\",\"authors\":\"Julie Goswami , Taleen A. MacArthur , Meera Sridharan , Julie Tange , Andrew J. Kirmse , Kaitlin A. 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引用次数: 2
摘要
与covid -19相关的凝血功能障碍尚不完全清楚。目的探讨急诊科(ED)凝血酶生成、血管性血友病因子(VWF)、中性粒细胞胞外陷阱(NETs)及其在COVID-19危险分层中的作用。患者/方法将67例ED COVID-19患者的血浆样本与38名健康志愿者(HVs)进行比较。凝血酶生成(校准的自动血栓图,CAT)表示为滞后时间(LT, min),峰高(PH, min)和峰时间(ttPeak, min)。用ELISA法定量瓜氨酸核小体和组蛋白,用乳胶免疫法定量VWF抗原和活性(IU/dL),用一期光学凝块法定量因子VIII (IU/dL),用Western blot密度法定量VWF多聚体。采用Wilcoxon检验和多变量logistic回归。结果以中位数[Q1, Q3]表示;p & lt;0.05意义重大。结果scovid -19患者LT延长(4.00 [3.26,4.67];[2.67, 3.10], p <0.001)和ttPeak (7.33 [6.33, 8.04];6.45 [6.00, 7.50], p = 0.004), VWF抗原升高(212 [158,275];[91,128], p <0.001)和因子VIII水平(148 [106,190];[86,129], p <0.001),高分子量多聚体减少(归一化多聚体比值0.807 [0.759,0.869];0.891 [0.858, 0.966], p <0.001),高于HVs。需要从急诊科入院的COVID-19患者比未入院的患者LT和ttPeak更长,VWF抗原和因子VIII水平更高。CAT参数和VWF的二变量和三变量模型与COVID-19和住院状态相关(c统计量为0.677 ~ 0.922)。结论凝血酶生成动力学和VWF水平可能在预测COVID-19患者入院需求方面具有独立于NETs的作用。
Biomarkers of thromboinflammation correlate to COVID-19 infection and admission status in emergency department patients
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.