The Impact of Hydroxyurea Use on Cognitive Functioning of Children with Sickle Cell Disease in Ghana

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-22
Author(s):  
Olubusola Oluwole ◽  
Amma owusu-Ansah ◽  
Seyed Mehdi Nouraie ◽  
Enrico M Novelli
Keyword(s):  
Working Memory ◽  
Cognitive Functioning ◽  
Sickle Cell ◽  
Organ Damage ◽  
Sub Saharan Africa ◽  
Psychomotor Function ◽  
Cell Disease ◽  
Sub Saharan ◽  
One Year ◽  
The Impact

Introduction: Sickle cell disease (SCD) is a genetic blood disorder characterized by a mutated hemoglobin that polymerizes when deoxygenated leading to sickle-shaped red blood cells. Tissue hypoxia and organ damage are downstream effects of red blood cell sickling. A manifestation of end organ damage that is of increasing concern, given its devastating functional effects, is cognitive impairment. Sub-Saharan Africa accounts for the highest annual SCD burden in the world, yet little is known about cognitive impairment in children from Africa with SCD. This knowledge gap inhibits the development of targeted interventions to prevent or mitigate cognitive deficits in children with SCD. In particular, it is unknown if hydroxyurea, the oldest FDA-approved drug for SCD, preserves cognitive functioning. The primary objective of this study was to assess the potential cognitive benefits of hydroxyurea administered over at least one year in children with SCD from Ghana. Methods: We conducted a cross-sectional study funded by an ASH Minority Resident Hematology Award at both the general pediatric sickle cell clinic and the hydroxyurea clinic at Korle Bu Teaching Hospital in Ghana. Children with a diagnosis of SCD (HbSS, HbSC and HbS/β-thalassemia) between the ages of 5 and 13 were approached and enrolled in two arms of the study - non-hydroxyurea and hydroxyurea groups - under an IRB-approved protocol. Children without any exposure to hydroxyurea were included in the non-hydroxyurea group while children who had been taking hydroxyurea for at least one year were included in the hydroxyurea group. Children's demographic data were obtained via an ad-hoc questionnaire. Anthropomorphic and laboratory data were obtained from the patients' charts. Cognitive function was assessed using Cogstate, a computer-based neurocognitive testing tool. A brief battery of tests was administered consisting of Detection, Identification, One Back and Groton Maze Learning tests, which assess psychomotor function, attention, working memory and executive functioning, respectively. We used multiple linear regression analysis and inverse proportional to weight propensity score analysis to test the association between hydroxyurea treatment and cognitive test scores. Results: We enrolled 58 children with SCD in the study, including 28 in the non-hydroxyurea group (mean age 9.2 ± 2.40, 54% girls), and 30 in the hydroxyurea group (mean age 9.2 ± 2.17, 57% girls). Children taking hydroxyurea had higher hemoglobin (9.34 vs 8.32 g/dL, P=0.02) and mean corpuscular volume values (94 ± 9.2 vs 77 ± 9.1 fL, P=<0.01) when compared to the non-hydroxyurea group. Children in the hydroxyurea group performed significantly better in the area of working memory (adjusted difference 0.19, p=0.02, Table 1), while there was no significant difference in the other domains. Other confounders including age, nutritional status, gender and subject education level did not impact the findings.Within the hydroxyurea group, increased transcranial doppler velocity in the left internal carotid and left anterior cerebral arteries (a stroke risk factor) was associated with worse psychomotor function (correlation coefficient 0.41, p=0.047). Conclusion:To our knowledge, this is the first study conducted in Africa to explore the impact of hydroxyurea on cognitive functioning. While causality cannot be inferred in this observational study, our results support the findings of a study conducted in the United States showing that children withSCD on hydroxyurea had improved cognitive functioning as compared to those not on the drug (Puffer et al.Child Neuropsychology. 2007). It is possible that hydroxyurea may result in improved cerebral oxygenation, potentially by ameliorating anemia. In a prior study we found that higher cognitive functioning in children with SCD is associated with higher maternal education (Oluwole et al.Pediatr Blood Cancer. 2016), however, the difference in working memory remained significant after adjusting for this variable. Future longitudinal and interventional studies are needed to further assess the potential benefits of hydroxyurea on cognitive functioning, particularly in sub-Saharan Africa, where other interventions aimed at reducing neurological complications of SCD, such as blood transfusions, remain limited. Disclosures No relevant conflicts of interest to declare.

scholarly journals Nutritional Perspectives On Sickle Cell Disease In Africa: A Systematic Review

2020 ◽  
Author(s):  
Eunice Berko Nartey ◽  
Jonathan Spector ◽  
Seth Adu-Afarwuah ◽  
Catherine L. Jones ◽  
Alan A. Jackson ◽  
...  
Keyword(s):  
Systematic Review ◽  
Sickle Cell Disease ◽  
Nutritional Status ◽  
Health Outcomes ◽  
Sickle Cell ◽  
Small Sample ◽  
Sub Saharan Africa ◽  
Cell Disease ◽  
Sub Saharan ◽  
The Impact

Abstract Background Sickle Cell Disease (SCD) is an inherited blood disorder and mostly affects individuals living in sub-Saharan Africa. Whilst there is an established link between its pathophysiology and nutritional status, research in this area in Africa is limited and evidence-based nutritional guidelines lacking. This systematic review aimed to evaluate studies in sub-Saharan Africa focused on nutritional aspects of SCD, codify results, and highlight gaps in knowledge that could inform priority-setting for future research. Methods The study was conducted using the Preferred Reporting items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We sought to include all studies involving original research of nutritional status of individuals (children and adults) with SCD in Africa. ‘Nutritional status’ was defined as topics related to dietary intake, measurements of growth or anthropometry, and nutritional-related biomarkers. Studies of anemia alone in non-SCD individuals were excluded as well as studies that assessed individuals with sickle cell trait (i.e., carriers). The databases used were Ovid Embase, Medline, Biosis and Web of Science. Studies conducted between 1995 and 2018 were included in the analyses. Results The search returned 366 articles from which 66 studies were included in the final analyses. Most investigations (70%) were conducted in Nigeria. Studies were categorized into one of three main categories: descriptive studies of anthropometric characteristics (47% of studies), descriptive studies of macro- or micronutrient levels (36% of studies), and interventional studies (14% of studies). There were fairly uniform findings that demonstrate that the growth of SCD patients in sub-Saharan Africa was impaired, especially in childhood and adolescence. Studies assessing macro- and micro-nutrients generally had small sample sizes and were exploratory in nature. Only two randomized, placebo-controlled trials were identified, which measured the impact of fatty acid supplementation and lime juice on health outcomes. Conclusions The findings of this review are consistent with data from other regional settings that describe a significant risk of malnutrition in individuals with SCD. There appears to be a substantial unmet need for clinical research to better understand the potential utility of nutritional-related interventions for patients with SCD in sub-Saharan Africa, to promote optimal growth and improve health outcomes.

Living with sickle cell disease: voices from sub-Saharan Africa

2021 ◽  
Author(s):  
Arafa Said Salim ◽  
Emmy Mwita ◽  
Joseph Sarfo Antwi ◽  
Olamide Agunkejoye ◽  
Paul Mdliva
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sub Saharan Africa ◽  
Cell Disease ◽  
Sub Saharan

Abstract 65: Anemia-related Heart Failure in Sub-saharan African Sickle Cell Disease Patients

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Adebayo C Atanda ◽  
Yahya Aliyu ◽  
Oluwafunmilayo Atanda ◽  
Aliyu Babadoko ◽  
Aisha Suleiman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Hemoglobin Level ◽  
Sub Saharan Africa ◽  
Cell Disease ◽  
Jet Velocity ◽  
Sub Saharan

Introduction: Anemia has been implicated in heart failure. Existing literatures, involving predominantly African-Americans, suggests that Sickle Cell Disease (SCD) maybe linked to various cardiovascular complications including pulmonary hypertension and left venticular dysfunction. Peculiarly, our study involves exclusively Sub-Saharan population. Method: We conducted a cross sectional observational study of 208 hydroxyurea-naive consecutive SCD patients aged 10-52 years at steady state and 94 healthy non-matched controls who were studied in an out patient clinic in Sub-Saharan Africa. SCD patients were required to have electrophoretic or liquid chromatography documentation of major sickling phenotypes. Control group was required to have non-sickling phenotypes. Cardiac measurements were performed with TransThoracic Echo according to American Society of Echocardiography guidelines. Hemoglobin level was also obtained. Results: Hemoglobin level in SCD group (8.5+/- 1.5) was significant (P<0.001) compared to control (13.8+/- 1.7). Although SCD group had significantly higher values of left ventricular (LV) size, there was no qualitative evidence of LV dysfunction. SCD group had higher values of Ejection Fraction but not statistically significant. There was no evidence of LV wall stiffening to impair proper filling in SCD group, with the ratio of early to late ventricular filling velocities, E/A ratio elevated (1.7+/-0.4 compared to 1.6+/- 0.4; P=0.010). Right ventricular systolic pressure was determined using the formula of 4x Tricuspid Reugurgitant jet (TRV) square as an indirect measurement of Pulmonary arterial systolic pressure. SCD patients had significantly higher mean±SD values for tricuspid regurgitant jet velocity than did the controls (2.1±0.6 vs. 1.8±0.5; p= 0.001). Within the SCD group, there was no clear pattern of worsening diastolic function with increased TRV. Furthermore, E/A had a significant positive relationship with jet velocity in bivariate analysis (R=0.20; P=0.013). Conclusions: We were unable to demonstrate existence of anemia-associated left ventricular dysfunction in Sub-Saharan African with SCD. Further studies is required to highlight the reason behind this finding.

scholarly journals Sickle Cell Disease Model Mice Lacking 2,3-Dpg Show Reduced RBC Sickling and Improvements in Markers of Hemolytic Anemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Kelly M. Knee ◽  
Amey Barakat ◽  
Lindsay Tomlinson ◽  
Lila Ramaiah ◽  
Zane Wenzel ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Organ Damage ◽  
Complete Elimination ◽  
Cell Disease ◽  
The Impact ◽  
2,3 Dpg

Sickle cell disease (SCD) is a severe genetic disorder caused by a mutation in hemoglobin (b6Glu-Val), which allows the mutant hemoglobin to assemble into long polymers when deoxygenated. Over time, these polymers build up and deform red blood cells, leading to hemolytic anemia, vaso-occlusion, and end organ damage. A number of recent therapies for SCD have focused on modulating the mutant hemoglobin directly, however, reduction or elimination of 2,3-DPG to reduce Hb S polymerization and RBC sickling has recently been proposed as a therapeutic strategy for SCD. Current clinical studies focus on activation of pyruvate kinase to reduce 2,3-DPG, however, direct targeting of the enzyme which produces 2,3-DPG; Bisphosphoglycerate Mutase (BPGM) may also be possible. In this study we evaluate the impact of elimination of 2,3-DPG on SCD pathology by complete knockout of BPGM in Townes model mice. Animals with complete knockout of BPGM (BPGM -/-) have no detectable 2,3-DPG, while animals that are heterozygous for BPGM (BPGM -/+) have 2,3-DPG levels comparable to Townes mice. Western Blot analysis confirms that BPGM -/- animals completely lack BPGM, while BPGM -/+ animals have BPGM levels that are nearly equivalent to Townes mice. As expected from the lack of 2,3-DPG, BPGM -/- animals have increased oxygen affinity, observed as a 39% decrease in p50 relative to Townes mice. Complete elimination of 2,3-DPG has significant effects on markers of hemolytic anemia in BPGM -/- mice. Mice lacking 2,3-DPG have a 60% increase in hemoglobin (3.7 g/dL), a 53% increase in red blood cell count, and a 29% increase in hematocrit relative to Townes mice. The BPGM -/- mice also have a 57% decrease in reticulocytes, and a 61% decrease in spleen weight relative to Townes animals, consistent with decreased extramedullary hematopoiesis. Consistent with the reduction in hemolysis, BPGM -/- animals had a 59% reduction in red blood cell sickling under robust hypoxic conditions. BPGM -/+ animals had hemoglobin, RBC, and hematocrit levels that were similar to Townes animals, and a similar degree of RBC sickling to Townes mice. Liver phenotype was similar across all variants, with areas of random necrosis observed in BPGM -/-, BPGM -/+ and Townes mice. Higher percentages of microcytic and/or hyperchromic RBCs were observed in BPGM -/- animals relative to BPGM -/+ or Townes animals. These results suggest that modulation of 2,3-DPG has a positive effect on RBC sickling and hemolytic anemia, which may have therapeutic benefits for SCD patients. However, the lack of improvement in organ damage suggests that modulation of 2,3-DPG alone may not be sufficient for complete elimination of SCD phenotypes, and further investigation of this therapeutic avenue may be necessary. Disclosures No relevant conflicts of interest to declare.

scholarly journals Advancing Healthcare Outcomes for Sickle Cell Disease in Nigeria Using Mobile Health Tools

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2173-2173
Author(s):  
Arwa Fraiwan ◽  
Muhammad Noman Hasan ◽  
Ran An ◽  
Amy J. Rezac ◽  
Nicholas J. Kocmich ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Mobile Health ◽  
Sub Saharan Africa ◽  
Diagnosis And Treatment ◽  
Test Results ◽  
Cell Disease ◽  
The World ◽  
Equity Ownership ◽  
Sub Saharan

Nigeria leads the world in the number of cases of sickle cell disease (SCD). An estimated 150,000 babies are born annually in Nigeria with SCD, a heredity disorder, and 70-90% die before age 5. Only a small portion of affected infants and children in sub Saharan Africa (SSA) reach adolescence. Over 650 children die per day in sub-Saharan Africa from SCD. These dismal statistics are in sharp contrast to outcomes in high-income countries (HICs) where more than 90% of SCD patients reach adulthood. The World Health Organization (WHO) estimates that 70% of deaths could be prevented with a low cost diagnostic and treatment plan. Meaningful preventive care and treatment cannot be implemented without a structured plan for early diagnosis and patient tracking.Early diagnosis requires improved access to parents and guardians of children with SCD, and gaining this access remains a challenge in most of SSA. In 2015, Nigeria's Kano state government, with support from foreign partners, established a community-based program for newborn registration. This platform provides unique access to newborn babies in one of Nigeria's most populous cities, but still lacks a functioning patient testing, tracking, and monitoring system, which we plan to address in our ongoing study. This study will introduce mobile health in a low-income country with low literacy rate and hopefully accustom that segment of the population to more varied mobile health applications that will ultimately improve their health in the long run. Our current operational platform in Kano, Nigeria provides access to a large population with a high prevalence of SCD. We have previously completed pilot testing of 315 subjects for SCD using our microchip electrophoresis test. We are planning to test up to 4,500 additional subjects less than 5 years of age at Murtala Muhammed Specialist Hospital. The hospital staff includes 97 physicians and 415 nurses and outpatient clinics serve about 30,000 patients monthly. The maternity department has a 200-bed capacity and the antenatal clinic performs about 1,000 deliveries and serves an average of 3,000 mothers monthly. Enrollment is planned to start on September 15, 2019 and medical staff are currently being trained to run the tests. Our study is registered in the United States National Library of Medicine's ClinicalTrials.gov (Identifier: NCT03948516). Our technology is uniquely paired with an automatic reader and an Electronic Medical Record (EMR) and patient management solution to record POC test results, register new cases, and track patients for follow-up (Fig. 1). The reader enables automated interpretation of test results, local and remote test data storage, and includes geolocation (Global Positioning System) (Fig. 2). The system will generate reports for all cases of SCD, track hospital visits, appointments, lab tests, and will have mobile and dashboard applications for tracking patients and samples. The application will be installed on mobile devices provided to users. The proposed system will be compliant with the existing privacy standards to handle medical data (e.g., HIPAA in the US and GDPR in the EU). All communications between the parties will be secured via end-to-end encryption as a safeguard. We anticipate that our project will increase the rates of screening, diagnosis and timely treatment of SCD in Kano State of Nigeria. The project's broader impact will likely be the ability to track and monitor screening, disease detection, diagnosis and treatment, which can be scaled up to the whole nation of Nigeria, then to sub-Saharan Africa. The data obtained and analyzed will be the first of their kind and will be used to inform the design of programs to improve access to, and availability of, effective care for this underserved populations. The importance of increased access to diagnosis and treatment should not be underestimated - it is crucial for realizing effective management of people with SCD. The impact can be enhanced by complementing diagnosis and patient tracking with education for the families so they can provide or seek the necessary preventative treatment. Identification of the location of the patients in need would help identify the areas where family, parent, caregiver education should be provided. Disclosures Fraiwan: Hemex Health, Inc.: Equity Ownership, Patents & Royalties. Hasan:Hemex Health, Inc.: Equity Ownership, Patents & Royalties. An:Hemex Health, Inc.: Patents & Royalties. Thota:Hemex Health, Inc.: Employment. Gurkan:Hemex Health, Inc.: Consultancy, Employment, Equity Ownership, Patents & Royalties, Research Funding.

scholarly journals Management of chronic respiratory complications in children and adolescents with sickle cell disease

2020 ◽  
Vol 29 (157) ◽  
pp. 200054
Author(s):  
Michele Arigliani ◽  
Atul Gupta
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Current Knowledge ◽  
Sub Saharan Africa ◽  
Cell Disease ◽  
Respiratory Complications ◽  
Progressive Decline ◽  
Blood Disorder ◽  
Life Threatening ◽  
Sub Saharan

Sickle cell disease (SCD) is a life-threatening hereditary blood disorder that affects millions of people worldwide, especially in sub-Saharan Africa. This condition has a multi-organ involvement and highly vascularised organs, such as the lungs, are particularly affected. Chronic respiratory complications of SCD involve pulmonary vascular, parenchymal and airways alterations. A progressive decline of lung function often begins in childhood. Asthma, sleep-disordered breathing and chronic hypoxaemia are common and associated with increased morbidity. Pulmonary hypertension is a serious complication, more common in adults than in children. Although there is a growing attention towards respiratory care of patients with SCD, evidence regarding the prognostic meaning and optimal management of pulmonary issues in children with this condition is limited.This narrative review presents state-of-the-art evidence regarding the epidemiology, pathophysiology and therapeutic options for chronic respiratory complications commonly seen in paediatric patients with SCD. Furthermore, it highlights the gaps in the current knowledge and indicates future directions for studies that aim to improve our understanding of chronic respiratory complications in children with SCD.

Epidemiology and treatment of relative anemia in children with sickle cell disease in sub-Saharan Africa

2016 ◽  
Vol 9 (11) ◽  
pp. 1031-1042 ◽  
Author(s):  
Halima Bello-Manga ◽  
Michael R. DeBaun ◽  
Adetola A. Kassim
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sub Saharan Africa ◽  
Cell Disease ◽  
Sub Saharan
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