Effects of hydroxyurea on fertility in male and female sickle cell disease patients. A systemic review and meta-analysis

Sewaralthahab, Sarah; Alsubki, Lujain A.; Alhrabi, Maram S.; Alsultan, Abdulrahman

doi:10.1371/journal.pone.0304241

Cited by 2 publications

References 64 publications

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CureSCi Metadata Catalog—finding and harmonizing studies for secondary analysis of hydroxyurea use for sickle cell disease

Wu,

Stratford,

Kesler

et al. 2024

Preprint

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Objectives: Sickle cell disease (SCD) is a rare group of inherited red blood cell disorders that affect hemoglobin, resulting in serious multi-system complications. The limited number of patients available to participate in research studies can inhibit investigating sophisticated relationships. Secondary analysis is a research method that involves using existing data to answer new research questions. Data harmonization enables secondary analysis by combining data across studies, especially helpful for rare disease research where individual studies may be small. The National Heart, Lung, and Blood Institute Cure Sickle Cell Initiative (CureSCi) Metadata Catalog is a web-based tool to identify SCD study datasets for conducting data harmonization and secondary analysis. We present a proof-of-concept secondary analysis to explore factors associated with discontinuation of hydroxyurea, a safe and effective first line SCD therapy, to illustrate the utility of the CureSCi Metadata Catalog to expedite and enable more robust SCD research. Methods: We performed secondary analysis of SCD studies using a multi-step workflow: develop research questions, identify study datasets, identify variables of interest, harmonize variables, and establish an analysis method. A harmonized dataset consisting of eight predictor variables across five studies was created. Secondary analysis involved a generalized linear model was employed to identify factors that significantly impact hydroxyurea discontinuation. Results: The CureSCi Metadata Catalog provided a platform to efficiently find relevant studies and design a harmonization strategy to prepare data for secondary analysis. Multivariate analysis of the harmonized identified that patients who are older, are female, had a history of blood transfusion therapy, had episodes of acute chest syndrome, and had the SC sickle cell genotype are more likely to stop hydroxyurea treatment. Conclusion: This secondary analysis provides a template for how the CureSCi Metadata Catalog expedites dataset discovery of sickle cell studies for identifying relationships between variables or validating existing findings.

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CureSCi Metadata Catalog—finding and harmonizing studies for secondary analysis of hydroxyurea use for sickle cell disease

Wu,

Stratford,

Kesler

et al. 2024

Preprint

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The Current Role of Hydroxyurea in the Treatment of Sickle Cell Anemia

López Rubio,

Argüello Marina

2024

JCM

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Despite advancements in treatment of sickle cell disease (SCD), hydroxyurea, a ribonucleotide reductase inhibitor, remains the cornerstone of therapy. While its primary effect is the elevation of fetal hemoglobin (HbF), hydroxyurea’s mechanisms of action are multifaceted. Hydroxyurea (HU) reduces leukocyte and platelet counts, decreases the expression of endothelial adhesion molecules CD36 and CD49d, and increases nitric oxide and cyclic nucleotide levels, which may facilitate vascular dilation and further HbF induction. Numerous studies have demonstrated that hydroxyurea therapy reduces the frequency of painful episodes, acute chest syndrome, and the need for erythrocyte transfusions and hospitalizations. Long-term use of hydroxyurea leads to reduced morbidity and mortality. Hydroxyurea should be initiated in children from 9 months of age, including asymptomatic individuals, and is recommended for adults experiencing pain crises that significantly interfere with daily activities or quality of life, as well as those with severe or recurrent vaso-occlusive crises, ACS, or severe symptomatic anemia. Hydroxyurea is not recommended during pregnancy or lactation due to potential teratogenic effects and transfer into breast milk. However, its use may be considered in high-risk patients, particularly during the second and third trimesters. Concerns about secondary tumor development have not been substantiated in long-term follow-up studies. Alternative therapies, including L-glutamine, crizanlizumab, and voxelotor, are not presently approved or available for clinical use in Europe.

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Effects of hydroxyurea on fertility in male and female sickle cell disease patients. A systemic review and meta-analysis

Cited by 2 publications

References 64 publications

CureSCi Metadata Catalog—finding and harmonizing studies for secondary analysis of hydroxyurea use for sickle cell disease

CureSCi Metadata Catalog—finding and harmonizing studies for secondary analysis of hydroxyurea use for sickle cell disease

The Current Role of Hydroxyurea in the Treatment of Sickle Cell Anemia

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