Association between Oxidative Stress, Genetic Factors, and Clinical Severity in Children with Sickle Cell Anemia

Renoux, Céline; Joly, Philippe; Faes, Camille; Mury, Pauline; Eglenen, Buse; Turkay, Mine; Yavas, Gokce; Yalçın, Özlem; Bertrand, Yves; Garnier, Nathalie; Cuzzubbo, Daniela; Gauthier, Alexandra; Romana, Marc; Möckesch, Berenike; Cannas, Giovanna; Antoine‐Jonville, Sophie; Pialoux, Vincent; Connes, Philippe

doi:10.1016/j.jpeds.2017.12.021

Cited by 24 publications

(19 citation statements)

References 55 publications

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“…This result needs confirmation for HbF since alpha‐globin has not been implied so far in the silencing process of the gamma‐globin genes. As for VOC rate, our findings are in accordance with the already described negative impact of alpha‐thalassemia –3.7 kb deletion on VOC occurrence . The most plausible pathophysiological explanation would be that alpha‐thalassemia –3.7 kb deletion would cause a reduction of the intracellular concentration of HbS, thus leading to a lower hemolytic rate, a higher hematocrit and more frequent VOC .…”

Section: Discussionsupporting

confidence: 91%

“…Co‐inheritance of one or two alpha‐thalassemia deletions protects from cerebral vasculopathy, cholelithiasis, leg ulcers, acute chest syndrome, and chronic kidney disease . These protective effects seem to be partly related to the effects of alpha‐thalassemia deletions on oxidative stress, red blood cell fragility, deformability, and hemolysis . In contrast, alpha‐thalassemia deletion would increase the risks for osteonecrosis and frequent vaso‐occlusive crises (VOC) because the lower hemolytic rate leads to a rise in blood viscosity .…”

Section: Introductionmentioning

confidence: 99%

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Combined and differential effects of alpha‐thalassemia and HbF‐quantitative trait loci in Senegalese hydroxyurea‐free children with sickle cell anemia

Tall

Martin

Ndour

et al. 2019

Pediatric Blood & Cancer

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Background:Our objective was to investigate the combined and differential effects of alphathalassemia -3.7 kb deletion and HbF-promoting quantitative trait loci (HbF-QTL) in Senegalese hydroxyurea (HU)-free children and young adults with sickle cell anemia (SCA).Procedure: Steady-state biological parameters and vaso-occlusive crises (VOC) requiring emergency admission were recorded over a 2-year period in 301 children with SCA. The age of the first hospitalized VOC was also recorded. These data were correlated with the alpha-globin and HbF-QTL genotypes. For the latter, three different genetic loci were studied (XmnI, rs7482144;BCL11A, rs1427407; and the HBS1L-MYB region, rs28384513) and a composite score was calculated, ranging from zero (none of these three polymorphisms) to six (all three polymorphisms at the homozygous state).Results: : A positive clinical impact of the HbF-QTL score on VOC rate, HbF, leucocytes, and Creactive protein levels was observed only for patients without alpha-thalassemia deletion. Conversely, combination of homozygous -3.7 kb deletion with three to six HbF-QTL was associated with a higher VOC rate. The age of the first hospitalized VOC was delayed for patients with one or two alpha-thalassemia deletions and at least two HbF-QTL.Conclusion: Alpha-thalassemia -3.7 kb deletion and HbF-QTL are modulating factors of SCA clinical severity that interact with each other. They should be studied and interpreted together and not separately, at least in HU-free children.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Combined and differential effects of alpha‐thalassemia and HbF‐quantitative trait loci in Senegalese hydroxyurea‐free children with sickle cell anemia

Tall

Martin

Ndour

et al. 2019

Pediatric Blood & Cancer

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“…NO can either be oxidized to nitrite and nitrate or reacts with hemoglobin or superoxide to form peroxynitrite, which would limit NO availability (see [61]). SCA patients show higher levels of reactive oxygen and nitrogen species compared to healthy controls [62]. Data of the present study showed reduced nitrotyrosine levels within the RBCs after training suggesting an increase in NO availability because of a reduction of nitrosative stress parameters.…”

Section: Discussionsupporting

confidence: 53%

Impact of A Six Week Training Program on Ventilatory Efficiency, Red Blood Cell Rheological Parameters and Red Blood Cell Nitric Oxide Signaling in Young Sickle Cell Anemia Patients: A Pilot Study

Grau

Nader

Jerke

et al. 2019

JCM

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Patients with sickle cell anemia (SCA) show impaired ventilatory efficiency, altered blood rheology, high levels of oxidative/nitrosative stress and enhanced hemolysis with large amounts of circulating free hemoglobin, which reduces nitric oxide (NO) bioavailability. The aim of the study was to investigate whether physical exercise could improve these physiological and biological markers described to contribute to SCA pathophysiology. Twelve SCA patients participated in a controlled six weeks training program with moderate volume (two sessions per week with 15–30 min duration per session) and intensity (70% of the first ventilatory threshold). Parameters were compared before (T0) and after (T1) training. Daily activities were examined by a questionnaire at T0 and one year after the end of T1. Results revealed improved ventilatory efficiency, reduced nitrosative stress, reduced plasma free hemoglobin concentration, increased plasma nitrite levels and altered rheology at T1 while no effect was observed for exercise performance parameters or hematological profile. Red blood cell (RBC) NO parameters indicate increased NO bioavailability which did not affect RBC deformability. Participants increased their daily life activity level. The data from this pilot study concludes that even low intensity activities are feasible and could be beneficial for the health of SCA patients.

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“…Renoux et al demostraron mediante un estudio realizado durante dos años en el Institute of Pediatric Hematology and Oncology de Lyon, Francia, que los niveles oxidativos están más elevados en pacientes con ACF a comparación de los pacientes que no la padecen, sin embargo, la tasa de eventos vaso oclusivos en los pacientes con esta condición no estaba relacionada con este fenómeno [23]. Finalmente, la deficiencia crónica de óxido nítrico (a raíz de los eventos vaso oclusivos y la respuesta compensatoria del organismo frente a los mismos), puede conllevar a la activación plaquetaria, aumento de la resistencia vascular periférica, disfunción endotelial, contribuyendo a los fenómenos inflamatorios y de remodelación a nivel arterial y venoso que conllevan, como es de esperarse, al desarrollo de vasculopatía [24].…”

Section: Fisiopatologíaunclassified

Anemia de Células Falciformes: Correlación Clínico-Patológica

Saavedra¹

2019

archmed

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La anemia de células falciformes es la alteración hematológica heredada más común a nivel mundial. Esta dada por la presencia de hemoglobinas anormales (HbS y sus diferentes genotipos) a raíz de una mutación en las cadenas de globina. La tríada clínica consiste en eventos vaso-oclusivos, anemia hemolítica crónica y asplenia funcional. Hoy en día se ha documentado toda clase de complicaciones asociadas a la enfermedad, entre las cuales se encuentran: accidentes cerebrovasculares, infarto agudo de miocardio, hipertensión pulmonar, tromboembolismos venosos, infecciones, necrosis de la papila renal, enfermedad renal crónica, ulceraciones en miembros inferiores, enfermedades del aparato hepatobiliar y necrosis ósea avascular. Es de vital importancia la realización de un correcto enfoque clínico y terapéutico de los pacientes con anemia de células falciformes de modo que sea posible la prevención y tratamiento oportuno de las complicaciones asociadas a esta condición.

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Association between Oxidative Stress, Genetic Factors, and Clinical Severity in Children with Sickle Cell Anemia

Cited by 24 publications

References 55 publications

Combined and differential effects of alpha‐thalassemia and HbF‐quantitative trait loci in Senegalese hydroxyurea‐free children with sickle cell anemia

Combined and differential effects of alpha‐thalassemia and HbF‐quantitative trait loci in Senegalese hydroxyurea‐free children with sickle cell anemia

Impact of A Six Week Training Program on Ventilatory Efficiency, Red Blood Cell Rheological Parameters and Red Blood Cell Nitric Oxide Signaling in Young Sickle Cell Anemia Patients: A Pilot Study

Anemia de Células Falciformes: Correlación Clínico-Patológica

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