Sickle cell disease

Kato, Gregory J.; Piel, Frédéric B.; Reid, Clarice D.; Gaston, Marilyn H.; Ohene‐Frempong, Kwaku; Krishnamurti, Lakshmanan; Smith, Wally R.; Panepinto, Julie A.; Weatherall, D. J.; Costa, Fernando Ferreira; Vichinsky, Elliott

doi:10.1038/nrdp.2018.10

Cited by 815 publications

(812 citation statements)

References 275 publications

(202 reference statements)

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“…Approximately 2000 babies are born with sickle cell disease (SCD) in the United States annually. Children with severe forms of SCD, including hemoglobin SS (HgbSS) and hemoglobin S beta 0 thalassemia (HgbSbeta 0 ), are at risk for severe anemia, vaso‐occlusive pain crisis, acute chest syndrome, splenic sequestration, central nervous system ischemia, and shortened life expectancy . High fetal hemoglobin (HgbF) is protective against sickle cell pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

Prospective longitudinal follow‐up of children with sickle cell disease treated with hydroxyurea since infancy

Thomas

Dulman

Lewis

et al. 2019

Pediatric Blood & Cancer

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Background Hydroxyurea (HU) increases fetal hemoglobin (HgbF) and ameliorates sickle cell disease (SCD) symptoms. Studies have demonstrated the safety and efficacy of HU in infants and children. Initiation of HU in infancy for children with SCD needs to be implemented in community practice. Procedure Starting in 2011, the Pediatric Sickle Cell Program of Northern Virginia initiated HU in infants with SCD. A prospective longitudinal database tracked the clinical course and outcomes. Results Twenty‐four children with HgbSS who started HU by age 1 were continuously followed for a total of 95 person‐years. Age at the time of analysis ranged from 2 to 7 years. Average hemoglobin at 6‐month intervals ranged from 9.5 + 1.9 to 10.7 + 0.8 g/dL, and average HgbF ranged from 27.8 + 5.0% to 34.1 + 6.6%. Twenty‐seven hospitalizations occurred (0.28/person‐year), all before age 3, including 19 (70%) for fever or infection, five (19%) for splenic sequestration, and one (4%) for pain in an infant prior to starting HU. The treat‐and‐release emergency department visits totaled 68 (0.72/person‐year), including 62 visits (91%) for fever, infection, or viral illness, and two visits (3%) for pain/dactylitis in infants before HU initiation. Splenic sequestration accounted for all five transfusions. No pain episodes requiring medical attention were documented after HU initiation. No complicated acute chest syndrome, no abnormal or conditional transcranial Doppler ultrasound, and no overt strokes occurred. Conclusion Implementation of HU in infancy for patients with SCD in community practice is feasible and is highly effective in preventing disease complications.

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Section: Introductionmentioning

confidence: 99%

Prospective longitudinal follow‐up of children with sickle cell disease treated with hydroxyurea since infancy

Thomas

Dulman

Lewis

et al. 2019

Pediatric Blood & Cancer

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“…Sickle cell disease (SCD) is recognized as an inherited hemoglobinopathy characterized by adhesion of blood cells, chronic hemolysis, and vascular occlusions. 1 SCD has diverse clinical complications. Among these, stroke is one of the most common and devastating complications.…”

Section: Introductionmentioning

confidence: 99%

Gene coexpression networks analysis of sickle stroke risk

Liu

Wang

et al. 2019

J of Cellular Biochemistry

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Stroke is one of the most destructive complications of sickle cell disease (SCD), and SCD is also the most common cause of childhood stroke. Sickle cell stroke is complex and has a genetic endothelial basis. Here, we further investigated this genetic basis using weighted gene coexpression network analysis. This systems biology approach revealed the correlation between coexpressed gene modules and sickle stroke risk. The pink module was significantly correlated with stroke risk and genes in this module were mainly related to GO:0044877 (protein‐containing complex binding). In addition hub genes were identified through protein‐protein interaction enrichment analysis, including CXCR7, VCAM1, CD44, BMP2, SMAD3, BCL2L1, ITPR2, ITPR3, etc. These hub genes were significantly enriched for three Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including “gastric acid secretion,” “pathways in cancer,” and “TGF‐ β signaling pathway.” Altogether, our results based on this innovative method provided some novel understanding of the pathology of sickle cell stroke. Hub genes identified in this study could be potential targets for screening and prevention of stroke risk in SCD children.

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“…Patients with SCD show a heterogeneous clinical presentation, ranging from mild clinical symptoms to death due to disease complications (Ballas et al , ). SCD complications are caused mainly by vaso‐occlusion and haemolysis (Yawn et al , ; Piel et al , ; Kato et al , ). Repeated vaso‐occlusive episodes in the spleen lead to loss of spleen function and atrophy in most SCD patients (Brousse et al , ).…”

mentioning

confidence: 99%

A Toll‐like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease

Tozatto-Maio

Girot

et al. 2019

Br J Haematol

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Summary Despite adequate immunization and penicillin prophylaxis, bacterial infections remain a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). Besides hyposplenism, inflammatory and genetic factors might modulate their susceptibility to bacterial infections. We performed a candidate gene association of single nucleotide polymorphisms (SNPs) located in Toll‐like receptor (TLR) genes, encoding prominent molecules for innate immune responses, with the occurrence of bacterial infections in patients with SCD. A cohort followed in centres in Brazil, France and Senegal (n = 430) was divided in two groups: patients who presented at least one episode of bacterial infection (n = 235) and patients who never had bacterial infections (n = 195). There were no differences in gender or age distribution among the groups. The frequency of the TLR2 rs4696480 TA genotype was significantly lower in the infected group (50% vs. 67%, odds ratio [OR] = 0·50, 95% confidence interval [CI] 0·34–0·75, P < 0·001), and the TT genotype was significantly higher in the infected group (15% vs. 5%, OR = 3·18, 95% CI 1·53–6·61, P < 0·001). Previous reports demonstrated higher secretion of inflammatory factors in cells from AA individuals, lower occurrence and severity of immune diseases in T carriers. The rs4696480 TA genotype might stand between deleterious effects of over inflammatory response (AA genotype) and inefficient responses (TT genotype) to infectious agents in SCD settings.

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Sickle cell disease

Cited by 815 publications

References 275 publications

Prospective longitudinal follow‐up of children with sickle cell disease treated with hydroxyurea since infancy

Prospective longitudinal follow‐up of children with sickle cell disease treated with hydroxyurea since infancy

Gene coexpression networks analysis of sickle stroke risk

A Toll‐like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease

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