Leg Ulcers in Sickle Cell Disease: a protocol for systematic review and meta-analysis

Abstract Background: Sickle cell disease affects about 112 per 100,000 live births globally. Leg ulcer is a major and clinically challenging complication of sickle cell disease. It affects about 1.0 -75 % of SCDs with exact prevalence unknown. This study aims to determine pooled prevalence of leg ulcer in sickle cell disease as well as evaluate moderating effects of single nucleotide polymorphisms, patient’s age and sex, geographical locations, treatment modalities and expression of plasma cytokines. Methods: A search strategy is developed using MeSH, text words and entry terms. Nine databases will be searched: PuMed, African Journal Online, Embase, Google Scholar, Scopus, Cochrane Library, CINAHL, Web of Science and ResearchGate. Only observational studies, retrievable in the English language will be included. The primary outcome is the proportion of leg ulcers in sickle cell disease. The effect size is prevalence. Identified studies will be screened and selected based on inclusion criteria using EndNote version 9. Quality scores and risk of bias for individual studies will be reported. Studies will be assessed for methodological, clinical, and statistical heterogeneity. Funnel Plots will be used to assess publication bias. Extracted data items will be arranged in Microsoft Excel before exporting them to CMA software for quantitative analysis. The random model computation for pooled effect size will be used. Results including pooled prevalence, standard error, 95 % CI and subgroup analysis will be presented in forest plots. Discussion: Ethical approval will not be required since this study is based on published data. This protocol will enable reproducible and accurate estimation of pooled prevalence of leg ulcers and effects of moderators in sickle cell disease. The data from such review will stimulate further research into leg ulcers in SCD. The final report of this study will be published in a peer-reviewed journal and the findings will be made available to various health experts that manage SCD patients especially haematologists. Trial Registration Number : This protocol is registered in PROSPERO; with registration number CRD42020213310.