ArticleHaematologica2013
The relationship between the severity of hemolysis, clinical manifestations and risk of death in 415 patients with sickle cell anemia in the US and Europe.
Article in Haematologica, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 125 papers, 6 of them syntheses that pooled it.
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.
Treatment of Pulmonary Hypertension and Sickle Cell Disease With Sildenafil Therapy
Comparative Effectiveness of a Decision Aid for Therapeutic Options in Sickle Cell Disease
Sickle Cell Disease (SCD) Biochip': Towards a Simple and Reliable Way to Monitor Sickle Cell Disease
Heart, Arteries and Sikle Cell Disease, a Multicentric Cohort of Cardiovascular Complications in Subsaharan Africa
A Substudy of the CADRE Study: Determination of Clinical Markers in Patients With Extreme Sickle Cell Disease Phenotype
Who cites it
125 citing papers in PubMed, 6 syntheses or guidelines pooled it, 217 citations in OpenAlex.
- AI-assisted decision support for sickle cell disease severity stratification using routine blood tests: a systematic review and meta-analysis.BMC medical informatics and decision making · 2026Pooled it
- Pooled it
- Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- Pooled it
- Risk factors for mortality in adult patients with sickle cell disease: a meta-analysis of studies in North America and Europe.Haematologica · 2017Pooled it
- Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel.Haematologica · 2014Guideline
- Riociguat in patients with sickle cell disease and hypertension or proteinuria (STERIO-SCD): a randomised, double-blind, placebo controlled, phase 1-2 trial.The Lancet. Haematology · 2024Trial
- Exercise-induced changes of vital signs in adults with sickle cell disease.American journal of hematology · 2021Trial
- Trial
- The CYB5R3American journal of hematology · 2020Trial
- B-type natriuretic peptide and plasma hemoglobin levels following transfusion of shorter-storage versus longer-storage red blood cells: Results from the TOTAL randomized trial.American heart journal · 2017Trial
- Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom.PloS one · 2014Trial
- Trial
- Elevated pulse pressure is associated with hemolysis, proteinuria and chronic kidney disease in sickle cell disease.PloS one · 2014Trial
- Genetic determinants of haemolysis in sickle cell anaemia.British journal of haematology · 2013Trial
- Haemolytic injury and cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Biomarkers for the diagnosis and phenotyping of acute chest syndrome in patients with sickle cell disease.Expert review of respiratory medicine · 2026Review
- BCL11A and HBS1L-MYB polymorphisms, in association with hydroxyurea and sex, modulate fetal hemoglobin levels in individuals with sickle cell anemia in the western region of Bahia, Brazil.Molecular biology reports · 2026Article
- Left ventricular strain and chamber dimensions in pediatric sickle cell disease: age-related reduction in myocardial deformation independent of hemolysis and hydroxyurea therapy.Haematologica · 2026Article
- Sex determines cardiac and renal Vulnerability to chronic hemoglobin toxicity.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 10 institutions in 2 countries.
Funding
Abstract
The intensity of hemolytic anemia has been proposed as an independent risk factor for the development of certain clinical complications of sickle cell disease, such as pulmonary hypertension, hypoxemia and cutaneous leg ulceration. A composite variable derived from several individual markers of hemolysis could facilitate studies of the underlying mechanisms of hemolysis. In this study, we assessed the association of hemolysis with outcomes in sickle cell anemia. A hemolytic component was calculated by principal component analysis from reticulocyte count, serum lactate dehydrogenase, aspartate aminotransferase and total bilirubin concentrations in 415 hemoglobin SS patients. Association of this component with direct markers of hemolysis and clinical outcomes was assessed. As primary validation, both plasma red blood cell microparticles and cell-free hemoglobin concentration were higher in the highest hemolytic component quartile compared to the lowest quartile (P≤0.0001 for both analyses). The hemolytic component was lower with hydroxyurea therapy, higher hemoglobin F, and alpha-thalassemia (P≤0.0005); it was higher with higher systemic pulse pressure, lower oxygen saturation, and greater values for tricuspid regurgitation velocity, left ventricular diastolic dimension and left ventricular mass (all P<0.0001). Two-year follow-up analysis showed that a high hemolytic component was associated with an increased risk of death (hazard ratio, HR 3.44; 95% confidence interval, CI: 1.2-9.5; P=0.02). The hemolytic component reflects direct markers of intravascular hemolysis in patients with sickle cell disease and allows for adjusted analysis of associations between hemolytic severity and clinical outcomes. These results confirm associations between hemolytic rate and pulse pressure, oxygen saturation, increases in Doppler-estimated pulmonary systolic pressures and mortality (Clinicaltrials.gov identifier: NCT00492531).
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Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.