Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia.

Platt, Orah S.; Orkin, Stuart H.; Dover, George J.; Beardsley, G. Peter; Miller, Barbara A.; Nathan, David G.

doi:10.1172/jci111464

Cited by 467 publications

(294 citation statements)

References 27 publications

(9 reference statements)

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“…Setting the stage for therapies targeting fetal hemoglobin, early studies noted that patients with SCA and higher fetal hemoglobin levels had fewer adverse clinical events such as pain episodes, stroke, and ACS [45,46]. The first significant clinical application of hydroxyurea was reported in 1984, when Platt et al demonstrated that hydroxyurea therapy increased fetal hemoglobin levels without significant marrow toxicity [47]. A second study of 10 adults with SCD demonstrated a 2-to 10-fold increase in fetal hemoglobin over 3 months of treatment with hydroxyurea [48].…”

Section: Hydroxyurea Therapymentioning

confidence: 99%

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

2015

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Over the past 40 years, public health measures such as universal newborn screening, penicillin prophylaxis, vaccinations, and hydroxyurea therapy have led to an impressive decline in sickle cell disease (SCD)-related childhood mortality and SCD-related morbidity in high-income countries. We remain cautiously optimistic that the next 40 years will be focused on meeting current challenges in SCD by addressing chronic complications of SCD to reduce mortality and improve quality of life in a growing population of adults with SCD in high-income countries, while simultaneously decreasing the disparity of medical care between high and low-income countries.

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Section: Hydroxyurea Therapymentioning

confidence: 99%

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

2015

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“…1 As many of the complications of sickle cell anemia (homozygosity for HBB, glu6val), like osteonecrosis, acute chest syndrome and painful episode, are associated with the level of HbF, and, HbF is inversely associated with mortality, investigators have assiduously sought pharmacological means of increasing HbF production. [2][3][4][5][6] Hydroxyurea (HU), a ribonucleotide reductase inhibitor, is one drug that increases HbF concentration in patients with sickle cell anemia [7][8][9][10] and it is the sole FDA-approved agent for treating sickle cell anemia. Most, but not all patients respond to HU treatment with an increase in HbF, but as with the baseline HbF concentration, which varies widely among patients, the magnitude of the HbF response to HU is also variable.…”

Section: Introductionmentioning

confidence: 99%

Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea

et al. 2007

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The increase in fetal hemoglobin (HbF) in response to hydroxyurea (HU) varies among patients with sickle cell anemia. Twenty-nine candidate genes within loci previously reported to be linked to HbF level (6q22.3-q23.2, 8q11-q12 and Xp22.2-p22.3), involved in metabolism of HU and related to erythroid progenitor proliferation were studied in 137 sickle cell anemia patients treated with HU. Three-hundred and twenty tagging single nucleotide polymorphisms (SNPs) for genotyping were selected based on HapMap data. Multiple linear regression and the nonlinear regression Random Forest method were used to investigate the association between SNPs and the change in HbF level after 2 years of treatment with HU. Both methods revealed that SNPs in genes within the 6q22.3-23.2 and 8q11-q12 linkage peaks, and also the ARG2, FLT1, HAO2 and NOS1 genes were associated with the HbF response to HU. Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU.

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“…David and his colleagues were also the first to show that hydroxyurea can stimulate fetal hemoglobin synthesis in sickle cell anemia (29,30). Large trials conducted by others, particularly George Dover and Samuel Charache (31), have since demonstrated that the treatment is clinically beneficial in at least half of the cases.…”

Section: Figurementioning

confidence: 99%

“…This article is adapted from a presentation at the ASCI/AAP Joint Meeting, April [28][29][30]2006, in Chicago, Illinois, USA.…”

Section: Acceptance Of the 2006 Kober Medalmentioning

confidence: 99%

Introduction of David G. Nathan, MD

Benz¹

2007

J. Clin. Invest.

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Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia.

Cited by 467 publications

References 27 publications

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea

Introduction of David G. Nathan, MD

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