Hydroxyurea use in sickle cell disease
- Griffin P Rodgers, MD
Griffin P Rodgers, MD
- Chief, Molecular and Clinical Hematology Branch
- National Institutes of Health
- Alex George, MD, PhD
Alex George, MD, PhD
- Assistant Professor of Pediatrics
- Baylor College of Medicine
- Section Editors
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Blood Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
- Donald H Mahoney, Jr, MD
Donald H Mahoney, Jr, MD
- Section Editor — Pediatric Hematology
- Professor of Pediatrics
- Baylor College of Medicine
The major causes of morbidity and mortality in sickle cell disease (SCD) are the acute and long-term consequences of vaso-occlusion and hemolysis, many of which cannot be reversed (eg, tissue infarction, vasculopathy). The approaches that are available for reducing these pathophysiologic processes are regular red blood cell (RBC) transfusions, hydroxyurea therapy, and hematopoietic cell transplantation (HCT).
This topic review discusses hydroxyurea therapy in SCD, including the mechanism of action, administration, dosing, and adverse effects. Separate topic reviews present overviews of SCD clinical manifestations and management, and the use of regular RBC transfusions and HCT in SCD:
●Clinical manifestations overview – (See "Overview of the clinical manifestations of sickle cell disease".)
●Management overview – (See "Overview of the management and prognosis of sickle cell disease".)
●Routine care for children – (See "Routine comprehensive care for children with sickle cell disease".)
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- MECHANISM OF ACTION
- Inhibition of ribonucleotide reductase
- Increased HbF production
- Other mechanisms
- Predictors of response
- INDICATIONS AND EVIDENCE FOR EFFICACY
- Indications and appropriate age to start therapy
- Evidence for efficacy
- - Improved survival
- - Reduced complications
- - Other benefits
- BASELINE TESTING
- ADMINISTRATION AND DOSING
- Initial dosing
- - Infants and young children
- - Older children, adolescents, and adults
- - Dosing in renal impairment
- Monitoring and dose titration
- Eliminating barriers to appropriate therapy
- Can therapy be discontinued?
- ADVERSE EFFECTS
- Falsely elevated serum creatinine and other laboratory tests
- Other toxicities
- Long-term effects
- SPECIAL SCENARIOS
- Lack of hematologic response
- Severe myelosuppression
- Transition from chronic transfusions to hydroxyurea
- Pregnancy and breastfeeding
- Resource-poor settings
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS