Comparisons of oxygen gradient ektacytometry parameters between sickle cell patients with or without α‐thalassaemia

Boisson, Camille; Renoux, Céline; Nader, Élie; Gauthier, Alexandra; Poutrel, Solène; Rab, Minke A.E.; Fort, Romain; Bertrand, Yves; Stauffer, Émeric; Cannas, Giovanna; Kébaïli, Kamila; Virot, E.; Hot, A.; Sheehan, Vivien A.; Beers, Eduard J. van; Wijk, Richard van; Joly, Philippe; Connes, Philippe

doi:10.1111/bjh.17777

Cited by 3 publications

(3 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Individuals with co‐inherited hetero‐ or homozygous α‐thalassaemia typically present with fewer organ or life‐threatening complications compared to individuals with no α‐thalassaemia deletions, although the incidence of acute pain is unchanged or possibly increased. A recent study by Boisson et al 21 . examined the impact of α‐thalassaemia genotype on Oxygenscan parameters in adults and children with HbSS.…”

Section: Discussionmentioning

confidence: 99%

“…19,20 Individuals with co-inherited hetero-or homozygous a-thalassaemia typically present with fewer organ or life-threatening complications compared to individuals with no a-thalassaemia deletions, although the incidence of acute pain is unchanged or possibly increased. A recent study by Boisson et al 21 examined the impact of athalassaemia genotype on Oxygenscan parameters in adults and children with HbSS. When comparing results from 12 individuals with homozygous a-thalassaemia to those from 97 individuals with heterozygous a-thalassaemia or no athalassaemia deletions, they found a significant difference in EI min and POS.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study by Boisson et al . 21 examined the impact of α-thalassaemia genotype on Oxygenscan parameters in adults and children with HbSS. When comparing results from 12 individuals with homozygous α-thalassaemia to those from 97 individuals with heterozygous α-thalassaemia or no α-thalassaemia deletions, they found a significant difference in EI min and POS.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Oxygen gradient ektacytometry does not predict pain in children with sickle cell anaemia

et al. 2021

View full text Add to dashboard Cite

The loss of red blood cell (RBC) deformability in sickle cell anaemia (SCA) is considered the primary factor responsible for episodes of acute pain and downstream progressive organ dysfunction. Oxygen gradient ektacytometry (Oxygenscan) is a recently commercialised functional assay that aims to describe the deformability of RBCs in SCA at differing oxygen tensions. So far, the Oxygenscan has been evaluated only by a small number of research groups and the validity and clinical value of Oxygenscan-derived biomarkers have not yet been fully established. In this study we examined RBC deformability measured with the Oxygenscan in 91 children with SCA at King's College Hospital in London. We found a significant correlation between Oxygenscan-derived biomarkers and well-recognised modifiers of disease severity in SCA: haemoglobin F and co-inherited a-thalassaemia. We failed, however, to find any independent predictive value of the Oxygenscan in the clinical outcome measure of pain, as well as other important parameters such as hydroxycarbamide treatment. Although the Oxygenscan remains an intriguing tool for basic research, our results question whether it provides any additional information in predicting the clinical course in children with SCA, beyond measuring known markers of disease severity.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Oxygen gradient ektacytometry does not predict pain in children with sickle cell anaemia

et al. 2021

View full text Add to dashboard Cite

show abstract

Genetic Variation and Sickle Cell Disease Severity

Kirkham,

Estepp,

Weiss

et al. 2023

JAMA Netw Open

View full text Add to dashboard Cite

ImportanceSickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD remain poorly understood.ObjectiveTo assess all reported genetic modifiers of SCD, evaluate the design of associated studies, and provide guidelines for future analyses according to modern genetic study recommendations.Data SourcesPubMed, Web of Science, and Scopus were searched through May 16, 2023, identifying 5290 publications.Study SelectionAt least 2 reviewers identified 571 original, peer-reviewed English-language publications reporting genetic modifiers of human SCD phenotypes, wherein the outcome was not treatment response, and the comparison was not between SCD subtypes or including healthy controls.Data Extraction and SynthesisData relevant to all genetic modifiers of SCD were extracted, evaluated, and presented following STREGA and PRISMA guidelines. Weighted z score meta-analyses and pathway analyses were conducted.Main Outcomes and MeasuresOutcomes were aggregated into 25 categories, grouped as acute complications, chronic conditions, hematologic parameters or biomarkers, and general or mixed measures of SCD severity.ResultsThe 571 included studies reported on 29 670 unique individuals (50% ≤ 18 years of age) from 43 countries. Of the 17 757 extracted results (4890 significant) in 1552 genes, 3675 results met the study criteria for meta-analysis: reported phenotype and genotype, association size and direction, variability measure, sample size, and statistical test. Only 173 results for 62 associations could be cross-study combined. The remaining associations could not be aggregated because they were only reported once or methods (eg, study design, reporting practice) and genotype or phenotype definitions were insufficiently harmonized. Gene variants regulating fetal hemoglobin and α-thalassemia (important markers for SCD severity) were frequently identified: 19 single-nucleotide variants in BCL11A, HBS1L-MYB, and HBG2 were significantly associated with fetal hemoglobin (absolute value of Z = 4.00 to 20.66; P = 8.63 × 10−95 to 6.19 × 10−5), and α-thalassemia deletions were significantly associated with increased hemoglobin level and reduced risk of albuminuria, abnormal transcranial Doppler velocity, and stroke (absolute value of Z = 3.43 to 5.16; P = 2.42 × 10−7 to 6.00 × 10−4). However, other associations remain unconfirmed. Pathway analyses of significant genes highlighted the importance of cellular adhesion, inflammation, oxidative and toxic stress, and blood vessel regulation in SCD (23 of the top 25 Gene Ontology pathways involve these processes) and suggested future research areas.Conclusions and RelevanceThe findings of this comprehensive systematic review and meta-analysis of all published genetic modifiers of SCD indicated that implementation of standardized phenotypes, statistical methods, and reporting practices should accelerate discovery and validation of genetic modifiers and development of clinically actionable genetic profiles.

show abstract

Blood rheology and vascular function in sickle cell trait and sickle cell disease: From pathophysiological mechanisms to clinical usefulness

Connes

2024

View full text Add to dashboard Cite

Sickle cell disease (SCD) is an autosomal recessive disorder. Although the molecular mechanisms at the origin of SCD have been well characterized, its clinical expression is highly variable. SCD is characterized by blood rheological abnormalities, increased inflammation and oxidative stress, and vascular dysfunction. Individuals with only one copy of the mutated β-globin gene have sickle cell trait (SCT) and are usually asymptomatic. The first part of this review focuses on the biological responses of SCT carriers during exercise and on the effects of combined SCT and diabetes on vascular function, several biomarkers and clinical complications. The second part of the review focuses on SCD and shows that the magnitude of red blood cell (RBC) rheological alterations is highly variable from one patient to another, and this variability reflects the clinical and hematological variability: patients with the less deformable RBCs have high hemolytic rate and severe anemia, and are prone to develop leg ulcers, priapism, cerebral vasculopathy, glomerulopathy or pulmonary hypertension. In contrast, SCD patients characterized by the presence of more deformable RBCs (but still rigid) are less anemic and may exhibit increased blood viscosity, which increases the risk for vaso-occlusive events. Several genetic and cellular factors may modulate RBC deformability in SCD: co-existence of α-thalassemia, fetal hemoglobin level, oxidative stress, the presence of residual mitochondria into mature RBCs, the activity of various non-selective cationic ion channels, etc. The last part of this review presents the effects of hydroxyurea and exercise training on RBC rheology and other biomarkers in SCD.

show abstract

Comparisons of oxygen gradient ektacytometry parameters between sickle cell patients with or without α‐thalassaemia

Cited by 3 publications

References 15 publications

Oxygen gradient ektacytometry does not predict pain in children with sickle cell anaemia

Oxygen gradient ektacytometry does not predict pain in children with sickle cell anaemia

Genetic Variation and Sickle Cell Disease Severity

Blood rheology and vascular function in sickle cell trait and sickle cell disease: From pathophysiological mechanisms to clinical usefulness

Contact Info

Product

Resources

About