Association of alpha‐thalassemia and Glucose‐6‐Phosphate Dehydrogenase deficiency with transcranial Doppler ultrasonography in Nigerian children with sickle cell anemia

Ojewunmi, Oyesola; Adeyemo, Titilope A.; Oyetunji, Ajoke Idayat; Benn, Yewande; Ekpo, Mfoniso Godwin; Iwalokun, Bamidele

doi:10.1002/jcla.23802

Cited by 7 publications

(7 citation statements)

References 37 publications

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“…Coexistent genetic factors in the study population, sample size, whether TAMMV or PSV was measured, and geographical spread of the participants might contribute to variation in the proportion of children with SCD who have conditional blood velocity in the cerebral arteries. A single-institution study in Nigeria showed that the coexistence of alpha thalassaemia trait protects against a rise in cerebral artery blood velocity, whereas no significant association with glucose-6-phosphate dehydrogenase was observed 23. That the parameter used could affect the proportion with conditional velocity is suggested by the similarity in the percentage in the TAMMV cohort in this study (10%) and that of 9.9% from another multicentre survey of children with SCD in Brazil during which TAMMV was measured 30…”

Section: Discussionmentioning

confidence: 99%

“…In Nigeria, the country that has the largest population of people with SCD (3 million) and the highest SCD birth rate of 150 000 per year,15–18 previous studies of the percentage who have conditional blood velocity in the cerebral arteries have been in single healthcare institutions and yielded variable results 19–24. The objective of this study is to obtain multicentre data to represent the general situation in the country and so facilitate the development of policy on the care of children with SCD who have conditional blood velocity in the cerebral arteries.…”

Section: Introductionmentioning

confidence: 99%

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Cerebral artery conditional blood velocity in sickle cell disease: a multicentre study and evidence for active treatment

et al. 2023

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ObjectiveTo obtain multicentre data on the prevalence of normal, high or conditional (intermediate) blood velocity in the cerebral arteries among children with sickle cell disease (SCD) in Nigeria.DesignA prospective observational study in five tertiary healthcare institutions. By transcranial Doppler (TCD) ultrasonography, cerebral artery peak systolic blood velocity (PSV) was determined in 193 children with SCD and time averaged mean of the maximum blood velocity (TAMMV) in a different cohort of 115 children. This design was to make the findings relevant to hospitals with TCD equipment that measure either PSV or TAMMV.SettingNigeria.Participants308 children (126 girls, 182 boys; age 2–16 years).Main outcome measuresPercentage of children with SCD who have normal, high or intermediate (often termed conditional) PSV or TAMMV.ResultsIn the cohort of 193 children, PSV was normal in 150 (77.7%), high in 7 (3.6%) and conditional in 36 (18.7%). In the cohort of 115 children, TAMMV was normal in 96 (84%), high in 7 (6%) and conditional in 12 (10%). There were no significant differences in gender or age distribution between the PSV and TAMMV cohorts. Altogether, cerebral artery blood velocity was normal in 246/308 children (80%), high in 14 (4.5%) and conditional in 48 (15.5%).ConclusionSince conditional blood velocity in cerebral arteries can progress to high values and predispose to stroke, the proportion of children with SCD who are affected (15.5%) raises the question of whether regular monitoring and proactive intervention ought to be the standard of care.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cerebral artery conditional blood velocity in sickle cell disease: a multicentre study and evidence for active treatment

et al. 2023

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“…Owing to the lack of facilities/resources, we did not assay the activity of vWF nor determine the presence of some genetic influencers of SCD, such as HbF and Alpha Thalassemia, which could impact several parameters in patients with SCA including the TCD velocity. 40,41 Despite these limitations, this study was able to establish, for the first time in our locality, that children with SCA had higher levels of FVIII and vWF. Furthermore, our study established that there exists a relationship between abnormal TCD velocity, platelet count, and left middle cerebral artery.…”

Section: Discussionmentioning

confidence: 77%

Relationships Between Transcranial Doppler Velocity, Von Willebrand Factor, Factor VIII, and Hematological Parameters in Children with Sickle Cell Anemia: A Comparative Cross-Sectional Study

Enifeni¹,

Ogbenna

Daramola³

et al. 2022

Clin Med�Insights�Blood�Disord

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Background and Objectives Sickle cell anemia (SCA) is associated with recurrent acute inflammatory processes. These inflammatory processes could lead to elevation of Factor VIII and Von Willebrand Factor levels, thereby increasing the risk of stroke in SCA children. This study aims to determine vWF/FVIII levels in children with SCA and their association with abnormal transcranial Doppler (TCD). Subjects and Methods This study enrolled 75 children, including 24 SCA cases with normal TCD, 27 SCA cases with abnormal TCD, and 24 Hb AA controls, all aged between 2 and 16 years. Transcranial Doppler (TCD) ultrasound was performed to measure the cerebral blood velocity. Venous blood drawn from each participant was used to determine the levels of von Willebrand Factor Antigen (vWF: Ag) and Factor VIII (FVIII) and the complete blood count (CBC). Relationships among the measured parameters were determined using SPSS version 25. Statistical significance was set at P < .05. Results FVIII and vWF levels were significantly higher among children with SCA compared to the Hb AA controls ( P < .001). Although SCA patients with abnormal TCD tended to have higher levels of FVIII and vWF, this result did not attain statistical significance ( P > .05). There was a moderate negative correlation between the left middle cerebral artery and FVIII, (r = −0.332; P = .017). Children with SCA showing an abnormal TCD velocity had significantly higher platelet count compared to those with normal TCD ( P = .018). Conclusion Children with SCA have elevated levels of FVIII and vWF, and an abnormal TCD velocity is associated with elevated platelet count.

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“…A total of 571 publications passed this screening (eFigure 1 in Supplement 1 , eTable 1 in Supplement 2 ). 8 , 11 , 12 , 13 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ...…”

Section: Methodsunclassified

Genetic Variation and Sickle Cell Disease Severity

Kirkham,

Estepp,

Weiss

et al. 2023

JAMA Netw Open

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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.

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Association of alpha‐thalassemia and Glucose‐6‐Phosphate Dehydrogenase deficiency with transcranial Doppler ultrasonography in Nigerian children with sickle cell anemia

Cited by 7 publications

References 37 publications

Cerebral artery conditional blood velocity in sickle cell disease: a multicentre study and evidence for active treatment

Cerebral artery conditional blood velocity in sickle cell disease: a multicentre study and evidence for active treatment

Relationships Between Transcranial Doppler Velocity, Von Willebrand Factor, Factor VIII, and Hematological Parameters in Children with Sickle Cell Anemia: A Comparative Cross-Sectional Study

Genetic Variation and Sickle Cell Disease Severity

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