Fraser Douglas D, Patterson Eric K, Slessarev Marat, Gill Sean E, Martin Claudio, Daley Mark, Miller Michael R, Patel Maitray A, Dos Santos Claudia C, Bosma Karen J, O'Gorman David B, Cepinskas Gediminas
Lawson Health Research Institute, London, ON, Canada.
Pediatrics, Western University, London, ON, Canada.
Crit Care Explor. 2020 Aug 24;2(9):e0194. doi: 10.1097/CCE.0000000000000194. eCollection 2020 Sep.
Coronavirus disease 2019 is caused by the novel severe acute respiratory syndrome coronavirus 2 virus. Patients admitted to the ICU suffer from microvascular thrombosis, which may contribute to mortality. Our aim was to profile plasma thrombotic factors and endothelial injury markers in critically ill coronavirus disease 2019 ICU patients to help understand their thrombotic mechanisms.
Daily blood coagulation and thrombotic factor profiling with immunoassays and in vitro experiments on human pulmonary microvascular endothelial cells.
Tertiary care ICU and academic laboratory.
All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had daily blood samples collected until testing was confirmed coronavirus disease 2019 negative on either ICU day 3 or ICU day 7 if the patient was coronavirus disease 2019 positive.
None.
Age- and sex-matched healthy control subjects and ICU patients that were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well balanced with the exception that coronavirus disease 2019 positive patients were more likely than coronavirus disease 2019 negative patients to suffer bilateral pneumonia. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Compared with healthy control subjects, coronavirus disease 2019 positive patients had higher plasma von Willebrand factor ( < 0.001) and glycocalyx-degradation products (chondroitin sulfate and syndecan-1; < 0.01). When compared with coronavirus disease 2019 negative patients, coronavirus disease 2019 positive patients had persistently higher soluble P-selectin, hyaluronic acid, and syndecan-1 ( < 0.05), particularly on ICU day 3 and thereafter. Thrombosis profiling on ICU days 1-3 predicted coronavirus disease 2019 status with 85% accuracy and patient mortality with 86% accuracy. Surface hyaluronic acid removal from human pulmonary microvascular endothelial cells with hyaluronidase treatment resulted in depressed nitric oxide, an instigating mechanism for platelet adhesion to the microvascular endothelium.
Thrombosis profiling identified endothelial activation and glycocalyx degradation in coronavirus disease 2019 positive patients. Our data suggest that medications to protect and/or restore the endothelial glycocalyx, as well as platelet inhibitors, should be considered for further study.
2019冠状病毒病由新型严重急性呼吸综合征冠状病毒2引起。入住重症监护病房（ICU）的患者会出现微血管血栓形成，这可能导致死亡。我们的目的是分析2019冠状病毒病ICU重症患者的血浆血栓形成因子和内皮损伤标志物，以帮助了解其血栓形成机制。
采用免疫测定法每日进行血液凝血和血栓形成因子分析，并对人肺微血管内皮细胞进行体外实验。
三级医疗ICU和学术实验室。
所有入住ICU怀疑感染严重急性呼吸综合征冠状病毒2的患者，采用标准化医院筛查方法，每日采集血样，直至在ICU第3天或第7天检测确认2019冠状病毒病呈阴性（如果患者2019冠状病毒病呈阳性）。
无。
纳入年龄和性别匹配的健康对照受试者以及2019冠状病毒病阳性或阴性的ICU患者。各队列情况良好平衡，唯一例外是2019冠状病毒病阳性患者比2019冠状病毒病阴性患者更易患双侧肺炎。2019冠状病毒病阳性ICU患者的死亡率为40%。与健康对照受试者相比，2019冠状病毒病阳性患者的血浆血管性血友病因子（<0.001）和糖萼降解产物（硫酸软骨素和多配体蛋白聚糖-1；<0.01）更高。与2019冠状病毒病阴性患者相比，2019冠状病毒病阳性患者的可溶性P选择素、透明质酸和多配体蛋白聚糖-1持续更高（<0.05），尤其是在ICU第3天及之后。在ICU第1至3天进行的血栓形成分析预测2019冠状病毒病状态的准确率为85%，预测患者死亡率的准确率为86%。用透明质酸酶处理去除人肺微血管内皮细胞表面的透明质酸会导致一氧化氮减少，这是血小板黏附于微血管内皮的一种激发机制。
血栓形成分析确定了2019冠状病毒病阳性患者的内皮激活和糖萼降解。我们的数据表明，应考虑进一步研究保护和/或恢复内皮糖萼的药物以及血小板抑制剂。
