Severity of Brazilian sickle cell disease patients: Severity scores and feasibility of the Bayesian network model use

Junior, Edis Belini; Silva, Danilo Grünig Humberto; Torres, Lidiane de Souza; Okumura, Jéssika Viviani; Lobo, Clarisse Lopes de Castro; Bonini-Domingos, Cláudia Regina

doi:10.1016/j.bcmd.2015.01.011

Cited by 20 publications

(12 citation statements)

References 51 publications

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“…As expected, in contrast to SCA patients who did not receive HU, those who received this treatment presented increased HbF levels and improvements in hemolytic, hepatic and inflammatory profiles (hemoglobin, hematocrit, MCV, MCH, reticulocytes, MCHC, RDW, AST, total bilirubin, LDH, WBC, neutrophils, eosinophils, lymphocytes, monocytes, platelets, and plateletcrit). These findings corroborate previous studies, which also demonstrated improvements in hemolytic, hepatic and inflammatory profiles in patients with SCA undergoing HU therapy (de Souza Santos and Maia, 2010;Voskaridou et al, 2010;de Souza Torres et al, 2012;Pallis et al, 2014;Belini Junior et al, 2015;Shome et al, 2016;Quarmyne et al, 2017;Colombatti et al, 2018). We further observed an increase in HDL-C concentration, demonstrating the effect of HU on lipid metabolism, which is consistent with our previous results (Yahouedehou et al, 2018b;Yahouedehou et al, 2019).…”

Section: Discussionsupporting

confidence: 93%

Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response

Yahouédéhou

Neres²,

Guarda

et al. 2020

Front. Pharmacol.

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Differences in hydroxyurea response in sickle cell anemia may arise due to a series of factors with genetic factors appearing to be predominant. This study aims to investigate the effects of single nucleotide polymorphisms in genes encoding drug-metabolizing enzymes and solute carriers on hydroxyurea response, in patients with sickle cell anemia. For that purpose, a total number of 90 patients with sickle cell anemia were recruited, 45 were undergoing hydroxyurea treatment, while 45 were not under the treatment. Association analyses were performed between CYP3A4 (rs2740574), CYP2D6 (rs3892097), CAT (rs7943316 and rs1001179), and SLC14A1 (rs2298720) variants and laboratory parameters. According to our findings, patients with hydroxyurea treatment demonstrated higher HbF levels and a significant improvement in hemolytic, hepatic, inflammatory, and lipid parameters in comparison to those without the treatment. We also found significant associations between the CYP2D6 (rs3892097), CAT (rs7943316 and rs1001179), and SLC14A1 (rs2298720) variants and an improvement of the therapeutic effects, specifically the hemolytic, hepatic, inflammatory, lipid, and renal parameters. In conclusion, our results highlight the importance of the investigated variants, and their strong association with hydroxyurea efficacy in patients with sickle cell anemia, which may be considered in the future as genetic markers.

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Section: Discussionsupporting

confidence: 93%

Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response

Yahouédéhou

Neres²,

Guarda

et al. 2020

Front. Pharmacol.

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“…The cytoreductive effect of HU, demonstrated by significant reductions in WBC, neutrophils, eosinophils and lymphocytes, is supported by other studies that also reported similar results [16,22,27,28]. In addition, we observed a significant decrease in levels of the anti-inflammatory protein AAT during HU therapy.…”

Section: Discussionsupporting

confidence: 91%

Hydroxyurea alters hematological, biochemical and inflammatory biomarkers in Brazilian children with SCA: Investigating associations with βS haplotype and α-thalassemia

et al. 2019

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This study investigated the effects of hydroxyurea (HU) on hematological, biochemical and inflammatory parameters in children with sickle cell anemia (SCA) in association with β S haplotype and α-thalassemia. We included 22 children with SCA who were followed for an average of 14.5 months. Laboratory parameters were assessed by electronic methods, and molecular analysis was investigated by PCR-RFLP and allele-specific PCR. Results showed significant increases in hemoglobin, HbF, hematocrit, MCV, MCH, glucose, HDL-C and albumin levels, as well as significant decreases in MCHC and AST levels, WBC, neutrophils, eosinophils, lymphocytes and reticulocytes, in children during HU therapy. HbF levels were positively correlated with hemoglobin, hematocrit, MCV and total protein, yet negatively correlated with MCHC, RDW, AAT and AST during HU therapy ( p <0.05). Children who carried the Central African Republic haplotype, in response to HU therapy, presented significant increases in hemoglobin, hematocrit, triglycerides and uric acid levels, as well as significant decreases in MCHC, AST and direct bilirubin levels, WBC, neutrophils, eosinophils, lymphocytes and reticulocytes. Those with the Benin haplotype presented increases in HbF and albumin levels, and a reduction in platelet counts ( p <0.05). Children with α-thalassemia presented decreased ALT during HU use, while those without this deletion presented increases in hemoglobin, hematocrit, MCV, MCH, HDL-C and albumin, as well as decreases in MCHC, neutrophils, lymphocytes, reticulocytes and AST ( p <0.05). Hence, regardless of its use in association with β S haplotypes or α-thalassemia, HU seems to be linked to alterations in hemolytic, inflammatory, hepatic, lipid and glycemic profiles.

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“…Using data from the Cooperative Study of Sickle Cell Disease (CSSCD), we generated a model of disease severity that integrated some biomarkers with complications of the disease to define an overall measure of disease severity that can predict death within five years 27 . This model, independently validated in part 28 , is useful to understand the relationships among clinical and laboratory measures of disease expression, although it is not designed to predict complications of the disease 29 . Recent work by Desai et al 30 discovered signatures based on a combination of blood mononuclear cell gene expression profiles and medical history of sickle cell disease patients to predict mortality.…”

Section: Introductionmentioning

confidence: 99%

Biomarker signatures of sickle cell disease severity

Ness

Nouraie

et al. 2018

Blood Cells, Molecules, and Diseases

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Identifying sickle cell disease patients at high risk of complications could lead to personalized treatment and better prognosis but despite many advances prediction of the clinical course of these patients remains elusive. We propose a system-type approach to discover profiles of multiple, common biomarkers that correlate with morbidity and mortality in sickle cell disease. We used cluster analysis to discover 17 signatures of 17 common circulating biomarkers in 2320 participants of the Cooperative Study of Sickle Cell Disease, and evaluated the association of these signatures with risk for stroke, pain, leg ulceration, acute chest syndrome, avascular necrosis, seizure, death, and trend of fetal hemoglobin and hemolysis using longitudinally collected data. The analysis shows that some of the signatures are associated with reduced risk for complications, while others are associated with increased risk for complications. We also show that these signatures repeat in two more contemporary studies of sickle cell disease and correlate with recently discovered biomarkers of pulmonary vascular disease. With replication and further study, these biomarker signatures could become an important and affordable precision medicine tool to aid treatment and management of the disease.

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Severity of Brazilian sickle cell disease patients: Severity scores and feasibility of the Bayesian network model use

Cited by 20 publications

References 51 publications

Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response

Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response

Hydroxyurea alters hematological, biochemical and inflammatory biomarkers in Brazilian children with SCA: Investigating associations with βS haplotype and α-thalassemia

Biomarker signatures of sickle cell disease severity

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