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Role of hydroxycarbamide in prevention of complications in patients with sickle cell disease

Authors Wiles N, Howard J

Published 21 September 2009 Volume 2009:5 Pages 745—755

DOI https://doi.org/10.2147/TCRM.S4769

Review by Single-blind

Peer reviewer comments 2

NM Wiles, J Howard

Department of Haematology, St Thomas’ Hospital, Westminster, Bridge Road, London, SE1 7EH, UK

Abstract: Sickle cell disease (SCD) is a genetically inherited condition caused by a point mutation in the beta globin gene. This results in the production of the abnormal hemoglobin, sickle hemoglobin (HbS). Hydroxycarbamide, is an antimetabolite/cytotoxic which works by inhibiting ribonucleotide reductase, blocking the synthesis of DNA and arresting cells in the S phase. In sickle cell anemia, it promotes fetal hemoglobin (HbF) synthesis, improves red cell hydration, decreases neutrophil and platelet count, modifies red cell endothelial cell interactions and acts as a nitric oxide donor. Trials have shown the clinical benefit of hydroxycarbamide in a subpopulation of adult patients with SCD, with a 44% reduction in the median annual rate of painful crises, a decrease in the incidence of acute chest syndrome and an estimated 40% reduction in overall mortality over a 9-year observational period. Its use in pediatrics has also been well established; trials have shown it is well tolerated and does not impair growth or development. In addition it decreases the number and duration of hospital attendences. A number of emerging uses of hydroxycarbamide currently are being investigated, such as stroke prevention.

Keywords: sickle cell anemia, hydroxycarbamide, hydroxyurea, maximum tolerated dose, vaso-occlusive crisis

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