Glucose‐6‐Phosphate Dehydrogenase Deficiency in Brazilian Children With Sickle Cell Anemia is not Associated With Clinical Ischemic Stroke or High‐Risk Transcranial Doppler

Belisário, André Rolim; Sales, Rahyssa Rodrigues; Toledo, Nayara Evelin; Velloso-Rodrigues, Cibele; Silva, Célia Maria; Viana, Marcos Borato

doi:10.1002/pbc.25924

Cited by 18 publications

(17 citation statements)

References 22 publications

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“…The reason for the geographic variations across continents is unclear but may be related to genetic and environmental differences. For example, the presence of alpha‐thalassaemia trait has been associated with lower TCD velocities (Hsu et al , ; Bernaudin et al , ; Cox et al , ; Belisario et al , ), while the concomitant inheritance of glucose‐6‐phosphate dehydrogenase (G6PD) deficiency as well as beta gene haplotypes may have a variable impact on TCD velocities and stroke (Flanagan et al , ; Alsultan et al , ; Cox et al , ; Belisario et al , ). There are emerging data that variation in environmental factors, such as weather and seasonality, as well as prevalence of bacteraemia or nutritional deficiency, such as vitamin D, across regions may underlie the variability of clinical expression of SCA‐related complications (Jones et al , ; Atkinson et al , ; Smith et al , ; Mekontso Dessap et al , ; Tayo et al , ).…”

Section: Discussionmentioning

confidence: 99%

Transcranial Doppler velocity among Jamaican children with sickle cell anaemia: determining the significance of haematological values and nutrition

et al. 2018

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This study investigated the association of nutritional and haematological variables with maximum time-averaged mean velocity (TAMV) measured by transcranial Doppler (TCD) velocity and the agreement of classification between two protocols. TCD categories included: normal (<170 cm/s), conditional (170-199 cm/s) and abnormal (≥200 cm/s) based on TAMV in distal internal carotid artery (dICA), middle cerebral artery (MCA), internal carotid bifurcation, anterior and posterior cerebral arteries. Of 358 children with sickle cell anaemia (SCA) examined, the mean age (±standard deviation) was 7·4 ± 2·7 years; 13·1% and 6·7% had conditional and abnormal velocities, respectively. Children with abnormal TCD velocities had higher prevalence of prior stroke (P = 0·006). Increased TAMV was associated with younger age (P = 0·001), lower weight (P = 0·001), height (P = 0·007) and oxygen saturation (P = 0·005). There was no association of TAMV with height-age or body mass index (BMI) z-scores. Adjusting for gender, BMI z-score, age, previous stroke and oxygen saturation, mean corpuscular volume (P = 0·005) and reticulocyte count (P = 0·013) were positively associated with TAMV, while haemoglobin concentration (P = 0·009) was negatively associated. There was good agreement [99%; weighted Kappa 0·98 (95% confidence interval 0·89-1), P = 0·0001] in TCD classification using data from five vessels versus two vessels (dICA and MCA). Haematological variables, rather than nutritional status, may be useful markers that identify high-risk children with SCA.

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Section: Discussionmentioning

confidence: 99%

Transcranial Doppler velocity among Jamaican children with sickle cell anaemia: determining the significance of haematological values and nutrition

et al. 2018

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“…21,22 Its effects on cerebrovascular disease are less clear. Some studies indicate no association between G6PD deficiency and stroke or cerebral vasculopathy, 17,23,24 while others do show an increased frequency of magnetic resonance index (MRI)- or transcranial Doppler (TCD)-defined cerebral vasculopathy. 18,25,26 These conflicting data limit the prognostic utility of G6PD deficiency.…”

Section: Determinants Modifiers and Correlates Of Disease Severitymentioning

confidence: 99%

Minireview: Clinical severity in sickle cell disease: the challenges of definition and prognostication

Quinn

2016

Exp Biol Med (Maywood)

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Sickle cell disease (SCD) is a monogenic, yet highly phenotypically variable disease with multisystem pathology. This manuscript provides an overview of many of the known determinants, modifiers, and correlates of disease severity in SCD. Despite this wealth of data, modeling the variable and multisystem pathology of SCD continues to be difficult. The current status of prediction of specific adverse outcomes and global disease severity in SCD is also reviewed, highlighting recent successes and ongoing challenges.

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“…In our experience, the prevalence of stroke or high-risk TCD was not significantly different in the groups with and without G6PD deficiency in a retrospective cohort study. 120 This absence of association has been reported in other studies that used molecular analysis as the diagnostic method for G6PD deficiency. 78 , 121 However, Thangarajh et al, 122 showed that the presence of the 376G (rs1050829) or 202A (rs1050828) allele was a significant and independent risk factor for intracranial MRA-arteriopathy in males with SCA.…”

Section: Methodsmentioning

confidence: 61%

“…The 376G allele leads to a very mild reduction in G6PD activity, as demonstrated in one study. 120 Children with the 376G allele (isoform A in males or AA in females) showed 85.2% of the enzymatic activity of G6PD when compared to individuals with the wild 376A allele (isoform B in males or BB in females). On the other hand, studies that reported an association between G6PD deficiency and abnormal TCD or intracranial stenosis used the measurement of G6PD activity as the method to define G6PD deficiency.…”

Section: Methodsmentioning

confidence: 99%

Genetic, laboratory and clinical risk factors in the development of overt ischemic stroke in children with sickle cell disease

Belisário

Silva

Velloso-Rodrigues

et al. 2018

Hematology, Transfusion and Cell Therapy

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Cerebrovascular disease, particularly stroke, is one of the most severe clinical complications associated with sickle cell disease and is a significant cause of morbidity in both children and adults. Over the past two decades, considerable advances have been made in the understanding of its natural history and enabled early identification and treatment of children at the highest risk. Transcranial Doppler screening and regular blood transfusions have markedly reduced the risk of stroke in children. However, transcranial Doppler has a limited positive predictive value and the pathophysiology of cerebrovascular disease is not completely understood. In this review, we will focus on the current state of knowledge about risk factors associated with ischemic stroke in patients with sickle cell disease. A search of PubMed was performed to identify studies. Full texts of the included articles were reviewed and data were summarized in a table. The coinheritance of alpha-thalassemia plays a protective role against ischemic stroke. The influence of other genetic risk factors is controversial, still preliminary, and requires confirmatory studies. Recent advances have established the reticulocyte count as the most important laboratory risk factor. Clinical features associated with acute hypoxemia as well as silent infarcts seem to influence the development of strokes in children. However, transcranial Doppler remains the only available clinical prognostic tool to have been validated. If our understanding of the many risk factors associated with stroke advances further, it may be possible to develop useful tools to detect patients at the highest risk early, improving the selection of children requiring intensification therapy.

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Glucose‐6‐Phosphate Dehydrogenase Deficiency in Brazilian Children With Sickle Cell Anemia is not Associated With Clinical Ischemic Stroke or High‐Risk Transcranial Doppler

Abstract: Our study demonstrated that G6PD molecular deficiency was not associated either with clinical ischemic stroke or high-risk TCD. Similarly, we found no associations between G6PD enzyme activity and stroke or high-risk TCD. Small sample size precludes definitive conclusions.

Cited by 18 publications

References 22 publications

Transcranial Doppler velocity among Jamaican children with sickle cell anaemia: determining the significance of haematological values and nutrition

Transcranial Doppler velocity among Jamaican children with sickle cell anaemia: determining the significance of haematological values and nutrition

Minireview: Clinical severity in sickle cell disease: the challenges of definition and prognostication

Genetic, laboratory and clinical risk factors in the development of overt ischemic stroke in children with sickle cell disease

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