ArticlePloS one2015
Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00011648 (Determining the Prevalence and Prognosis of Secondary Pulmonary Hypertension in Adult Patients With Sickle Cell Anemia), which is not on this map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Determining the Prevalence and Prognosis of Secondary Pulmonary Hypertension in Adult Patients With Sickle Cell Anemia
Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
- Trial
- Adding hydroxyurea to chronic transfusion therapy for sickle cell anemia reduces transfusion burden.Transfusion · 2025Trial
- A multilevel mHealth intervention boosts adherence to hydroxyurea in individuals with sickle cell disease.Blood advances · 2023Trial
- "Maximum tolerated dose" vs "fixed low-dose" hydroxyurea for treatment of adults with sickle cell anemia.American journal of hematology · 2019Trial
- Population Pharmacokinetic and Exposure-Response Analyses of Prasugrel in Pediatric Patients with Sickle Cell Anemia.Clinical pharmacokinetics · 2018Trial
- Excellent clinical and patient-reported outcomes following matched sibling donor BMT for sickle cell disease.Bone marrow transplantation · 2026Article
- Management of Kidney Disease with Sickle Cell Disease.Journal of the American Society of Nephrology : JASN · 2025Review
- Buprenorphine Is Associated With Lower Home Opioid Use and Acute Care Utilization in Sickle Cell Disease.Pain management nursing : official journal of the American Society of Pain Management Nurses · 2025Article
- Nonmyeloablative Pentostatin-Cyclophosphamide Preconditioning Improves Rates of Engraftment in Adults Undergoing Haploidentical HCT for Sickle Cell Disease.medRxiv : the preprint server for health sciences · 2025Article
- Pulmonary Hypertension Among Individuals Living With Hemoglobinopathies: A Systematic Review.Cureus · 2025Review
- Lipid Levels Increase to the Normal Range After Nonmyeloablative Hematopoietic Cell Transplantation for Sickle Cell Disease.Transplantation and cellular therapy · 2025Article
- Empirically derived profiles of neurocognitive functioning in youth and young adults with sickle cell disease.Journal of pediatric psychology · 2024Article
- End Organ Affection in Sickle Cell Disease.Cells · 2024Review
- Intensive hydroxyurea dosing in very young children with sickle cell anemia.Blood advances · 2023Article
- Creating an automated contemporaneous cohort in sickle cell anemia to predict survival after disease-modifying therapy.Blood advances · 2023Article
- Defining global strategies to improve outcomes in sickle cell disease: a Lancet Haematology Commission.The Lancet. Haematology · 2023Review
- Editing the core region in HPFH deletions alters fetal and adult globin expression for treatment of β-hemoglobinopathies.Molecular therapy. Nucleic acids · 2023Article
- Fetal hemoglobin modulates neurocognitive performance in sickle cell anemiaCurrent research in translational medicine · 2022Article
- Single Nucleotide Polymorphisms inDiagnostics (Basel, Switzerland) · 2022Review
- Long-Term Health Effects of Curative Therapies on Heart, Lungs, and Kidneys for Individuals with Sickle Cell Disease Compared to Those with Hematologic Malignancies.Journal of clinical medicine · 2022Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundAdults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea.
objectivesWe retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010.
methodsAn electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648.
resultsThree hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003-1.006, p<0.0.0001), kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00-1.27, p = 0.043), and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23-4.02, p = 0.0082). Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34-0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15-35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17-0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels.
conclusionsOur data suggest that adults should be treated with the maximum tolerated hydroxyurea dose, ideally before organ damage occurs. Prospective studies are indicated to validate these findings.
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Registered trials
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