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Meta-Analysis
. 2022 Oct:218:83-98.
doi: 10.1016/j.thromres.2022.08.017. Epub 2022 Aug 18.

Prognostic value of von Willebrand factor and ADAMTS13 in patients with COVID-19: A systematic review and meta-analysis

Xin Xu  1 , Yao Feng  2 , Yitong Jia  3 , Xiao Zhang  2 , Long Li  2 , Xuesong Bai  2 , Liqun Jiao  4
Affiliations
Meta-Analysis

Prognostic value of von Willebrand factor and ADAMTS13 in patients with COVID-19: A systematic review and meta-analysis

Xin Xu et al. Thromb Res. 2022 Oct.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: ADAMTS13; COVID-19; SARS-CoV-2; von Willebrand factor.

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Conflict of interest statement

Declaration of competing interest The authors declare no competing interest in this work.

Figures

Fig. 1
Fig. 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.
Fig. 2
Fig. 2
Forest plot of the association between VWF:Ag and composite clinical outcomes.
Fig. 3
Fig. 3
Forest plot of the association between VWF:Rco and composite clinical outcomes.
Fig. 4
Fig. 4
Forest plot of the association between ADAMTS13:Ac and composite clinical outcomes.
Fig. 5
Fig. 5
Forest plot of the association between VWF:Ag/ADAMTS13:Ac ratio and composite clinical outcomes.
Fig. 6
Fig. 6
Forest plot of the association between FVIII and composite clinical outcomes.
See this image and copyright information in PMC

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