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To evaluate the contributions of VWF to the clinical manifestation and severity of SCD A systematic review of peer-reviewed articles published in English. The review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. The data sources for the review included MEDLINE, PubMed, CINAHL, and Academic Search Complete. Articles that applied a quantitative approach to the investigation of the relationship of vWF with clinical manifestations and severity indices were included. The risk of bias assessment was carried out with a mixed-method appraisal tool. We computed I  2  to estimate the degree of heterogeneity. There was a significantly higher level of VWF in SCD than in the control (d = 2.7, Z = 4.865, P &lt; 0.001, I  2  = 96.41%). Significant positive correlations were obtained for the relationship of VWF with vasoocclusive crisis (r= 0.277, Z= 5.077, P &lt; 0.001, 1  2  =15.62), rate of hemolysis (r=0.441; Z= 4.440, I  2  = &lt;1%), extracellular haemoglobin (r=-0.397, Z=-4.155, I  2  =&lt;1%) and CRP (r = 0.331, Z = 4.566, P &lt; 0.001, I  2  &lt; 1%). The VWF is important in determining the clinical severity of sickle cell disease, which constitutes a putative therapeutic target. More work is required to understand the causal direction underlying the association between VWF levels and the clinical severity of sickle cell disease and the potential role that VWF plays in the clinical manifestations of sickle cell disease. The protocol was registered with PROSPERO (CRD42021262625).

Contributions of von Willebrand factor to clinical severity of sickle cell disease: a systematic review and metanalysis