Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, China; China International Neuroscience Institute (China-INI), 45 Changchun Street, Beijing, China.
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, China; China International Neuroscience Institute (China-INI), 45 Changchun Street, Beijing, China.
Thromb Res. 2022 Oct;218:83-98. doi: 10.1016/j.thromres.2022.08.017. Epub 2022 Aug 18.
Endotheliopathy and coagulopathy appear to be the main causes for critical illness and death in patients with coronavirus disease 2019 (COVID-19). The adhesive ligand von Willebrand factor (VWF) has been involved in immunothrombosis responding to endothelial injury. Here, we reviewed the current literature and performed meta-analyses on the relationship between both VWF and its cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) with the prognosis of COVID-19.
We searched MEDLINE, Cochrane Library, Web of Science, and EMBASE databases from inception to 4 March 2022 for studies analyzing the relationship between VWF-related variables and composite clinical outcomes of patients with COVID-19. The VWF-related variables analyzed included VWF antigen (VWF:Ag), VWF ristocetin cofactor (VWF:Rco), ADAMTS13 activity (ADAMTS13:Ac), the ratio of VWF:Ag to ADAMTS13:Ac, and coagulation factor VIII (FVIII). The unfavorable outcomes were defined as mortality, intensive care unit (ICU) admission, and severe disease course. We used random or fixed effects models to create summary estimates of risk. Risk of bias was assessed based on the principle of the Newcastle-Ottawa Scale.
A total of 3764 patients from 40 studies were included. The estimated pooled means indicated increased plasma levels of VWF:Ag, VWF:Rco, and VWF:Ag/ADAMTS13:Ac ratio, and decreased plasma levels of ADAMTS13:Ac in COVID-19 patients with unfavorable outcomes when compared to those with favorable outcomes (composite outcomes or subgroup analyses of non-survivor versus survivor, ICU versus non-ICU, and severe versus non-severe). In addition, FVIII were higher in COVID-19 patients with unfavorable outcomes. Subgroup analyses indicated that FVIII was higher in patients admitting to ICU, while there was no significant difference between non-survivors and survivors.
The imbalance of the VWF-ADAMTS13 axis (massive quantitative and qualitative increases of VWF with relative deficiency of ADAMTS13) is associated with poor prognosis of patients with COVID-19.
内皮病和凝血病似乎是导致 2019 年冠状病毒病（COVID-19）患者发生重症和死亡的主要原因。黏附配体血管性血友病因子（VWF）参与了对内皮损伤的免疫血栓形成反应。在这里，我们综述了目前关于 VWF 及其裂解蛋白酶 ADAMTS13（一种带有血小板反应蛋白 1 型基序的解整合素和金属蛋白酶，成员 13）与 COVID-19 预后之间关系的文献，并进行了荟萃分析。
我们从建库到 2022 年 3 月 4 日，在 MEDLINE、Cochrane 图书馆、Web of Science 和 EMBASE 数据库中检索了分析 VWF 相关变量与 COVID-19 患者复合临床结局之间关系的研究。分析的 VWF 相关变量包括 VWF 抗原（VWF：Ag）、VWF 瑞斯托菌素辅因子（VWF：Rco）、ADAMTS13 活性（ADAMTS13：Ac）、VWF：Ag 与 ADAMTS13：Ac 的比值以及凝血因子 VIII（FVIII）。不良结局定义为死亡率、入住重症监护病房（ICU）和严重疾病过程。我们使用随机或固定效应模型创建风险的汇总估计值。基于纽卡斯尔-渥太华量表的原则评估偏倚风险。
共纳入了来自 40 项研究的 3764 名患者。与预后良好的患者相比，预后不良（复合结局或亚组分析，包括非幸存者与幸存者、入住 ICU 与非 ICU、以及重症与非重症）的 COVID-19 患者的血浆 VWF：Ag、VWF：Rco 和 VWF：Ag/ADAMTS13：Ac 比值升高，ADAMTS13：Ac 水平降低。此外，预后不良的 COVID-19 患者的 FVIII 水平升高。亚组分析表明，入住 ICU 的患者的 FVIII 水平较高，而在非幸存者与幸存者之间，没有显著差异。
VWF-ADAMTS13 轴的失衡（VWF 的大量定量和定性增加与 ADAMTS13 的相对缺乏有关）与 COVID-19 患者的不良预后相关。
