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Effect of Hydroxyurea on the Frequency of Painful Crises in Sickle Cell Anemia
Open accessAbstract
BACKGROUND: In a previous open-label study of hydroxyurea therapy, the synthesis of fetal hemoglobin increased in most patients with sickle cell anemia, with only mild myelotoxicity. By inhibiting sickling, increased levels of fetal hemoglobin might decrease the frequency of painful crises. METHODS: In a double-blind, randomized clinical trial, we tested the efficacy of hydroxyurea in reducing the frequency of painful crises in adults with a history of three or more such crises per year. The trial was stopped after a mean follow-up of 21 months. RESULTS: Among 148 men and 151 women studied at 21 clinics, the 152 patients assigned to hydroxyurea treatment had lower annual rates of crises than the 147 patients given placebo (median, 2.5 vs. 4.5 crises per year, P < 0.001). The median times to the first crisis (3.0 vs. 1.5 months, P = 0.01) and the second crisis (8.8 vs. 4.6 months, P < 0.001) were longer with hydroxyurea treatment. Fewer patients assigned to hydroxyurea had chest syndrome (25 vs. 51, P < 0.001), and fewer underwent transfusions (48 vs. 73, P = 0.001). At the end of the study, the doses of hydroxyurea ranged from 0 to 35 mg per kilogram of body weight per day. Treatment with hydroxyurea did not cause any important adverse effects. CONCLUSIONS: Hydroxyurea therapy can ameliorate the clinical course of sickle cell anemia in some adults with three or more painful crises per year. Maximal tolerated doses of hydroxyurea may not be necessary to achieve a therapeutic effect. The beneficial effects of hydroxyurea do not become manifest for several months, and its use must be carefully monitored. The long-term safety of hydroxyurea in patients with sickle cell anemia is uncertain.
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“inhibition of HbS polymerization with hydroxyurea reduces the incidence of ACS (205).”
From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [205]
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In the citing paper
“By inducing increased levels of HbF through mechanisms that include suppressing erythropoiesis, hydroxyurea was first associated with reduction of morbidity and mortality in adults.81,82”
From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [81]
Experimental — accuracy not yet measuredIn the citing paper
“Administration of hydroxyurea has been shown to induce expression of HbF, which interferes with the polymerization of HbS (33).”
From Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia (2017) · cites this paper as [33]
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Rees, D. C., Williams, T. N., & Gladwin, M. T. (2010) · The Lancet · doi:10.1016/s0140-6736(10)61029-x · Cited by 2,504
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Metadata
- Authors
- Charache, S., Terrin, M. L., Moore, R. D., Dover, G. J., Barton, F. B., Eckert, S. V., McMahon, R. P., & Bonds, D. R.
- Affiliations
- Johns Hopkins University (US)
- Maryland Medical Research Institute (US)
- National Heart, Lung, and Blood Institute (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1995-05-18
- Volume
- 332
- Issue
- 20
- Pages
- 1317-1322
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2313541759
- Semantic Scholar
- 2c0939e2f6480b519903bb15870e5b894887e70d
- Cited by
- 2,340
- References
- 26
- Citations by year
- 2026: 67 · 2025: 97 · 2024: 77 · 2023: 88 · 2022: 95 · 2021: 92 · 2020: 80 · 2019: 78 · 2018: 85 · 2017: 104 · 2016: 114 · 2015: 101 · 2014: 82 · 2013: 79 · 2012: 73
- FWCI
- 34.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- National Institutes of Health (5u01hl045696-05)
- National Heart, Lung, and Blood Institute (UO1-HL 45696, UO1 HL 45692, U01HL045692)
- National Center for Research Resources (RR00046, M01RR000046)
- Topics
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Health Sciences › Medicine › Hematology › Hemophilia Treatment and Research
- Keywords
- hydroxyurea, sickle cell disease, vaso-occlusive crisis, fetal hemoglobin, blood transfusion, myelosuppression, treatment efficacy, adverse effects
- MeSH terms
- Adult, Anemia, Sickle Cell, Double-Blind Method, Female, Follow-Up Studies, Humans, Hydroxyurea, Male, Pain
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