内皮病和凝血病似乎是2019年冠状病毒病患者危重疾病和死亡的主要原因(COVID-19)。粘附配体vonWillebrand因子(VWF)已参与响应内皮损伤的免疫血栓形成。这里,我们回顾了目前的文献,并对VWF及其裂解蛋白酶ADAMTS13(一种具有血小板反应蛋白1型基序的整合素和金属蛋白酶,成员13)与COVID-19的预后。
我们搜索了MEDLINE,科克伦图书馆,WebofScience,和EMBASE数据库从开始到2022年3月4日,用于分析VWF相关变量与COVID-19患者复合临床结局之间的关系。分析的VWF相关变量包括VWF抗原(VWF:Ag),VWF维生素C辅因子(VWF:Rco),ADAMTS13活性(ADAMTS13:Ac),VWF:Ag与ADAMTS13:Ac的比率,和凝血因子VIII(FVIII)。不利结果定义为死亡率,重症监护病房(ICU)入院,和严重的疾病过程。我们使用随机或固定效应模型来创建风险的汇总估计。根据纽卡斯尔-渥太华量表的原则评估偏倚风险。
共纳入40项研究的3764名患者。估计的汇总平均值表明VWF:Ag的血浆水平升高,VWF:Rco,和VWF:Ag/ADAMTS13:Ac比,与预后良好的COVID-19患者相比,预后不良的COVID-19患者的血浆ADAMTS13:Ac水平降低(非幸存者与幸存者的复合结局或亚组分析,ICU与非ICU,以及严重与非严重)。此外,结果不利的COVID-19患者的FVIII更高。亚组分析表明,入住ICU的患者FVIII较高,而非幸存者和幸存者之间没有显着差异。
VWF-ADAMTS13轴的失衡(VWF的大量定量和定性增加,ADAMTS13相对缺乏)与COVID-19患者的不良预后相关。
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.