Point-of-Care Newborn Screening for Sickle Cell Disease at Selected Health Facilities in the Gambia.

Sickle cell disease (SCD) contributes significantly to childhood morbidity and mortality in sub-Saharan Africa. Early diagnosis through newborn screening (NBS) and subsequent comprehensive follow-up care will reduce the burden. Up till now, the prevalence of SCD among newborns remains unknown in The Gambia and there is no national NBS programme to address this significant public health issue. We assessed the real-time frequency of SCD in the country and determined differences in the pattern of SCD phenotypes among different ethnic groups. A preliminary prospective feasibility study was done in eight purposively selected hospitals in the seven Health Administrative Regions and Banjul. Consecutive newborn babies delivered or managed in these facilities were screened using HemoTypeSC, a sensitive and specific ELISA-based point-of-care test (POCT). Babies identified as SCD with HemoTypeSC were retested at age ≥6 months using alkaline cellulose acetate hemoglobin electrophoresis (ACAE). Head-to-head comparison between HemoType screening and gold standard HPLC could not be done. 1,168 newborn babies were screened from April 14 to August 12, 2023. Fifteen (1.3%) had homozygous HbS (HbSS), two (0.2%) heterozygous for HbS and HbC (HbSC), 204 (17.5%) had sickle cell trait (HbAS), four (0.3%) heterozygous for HbA and HbC (HbAC), and 943 (80.7%) had normal hemoglobin (HbAA). The 17 with SCD (HbSS and HbSC) comprised of 7 (2.2%) of 324 Fula; 6 (1.4%) of 426 Mandinka; 2 (1.6%) of 125 Jola and 2 (1.3%) of 150 Wolof. Fourteen (82.4%) of the 17 accepted the diagnosis and were enrolled into the SCD program. For these 14, HemoTypeSC had 100% sensitivity with ACAE when repeated at age ≥6 months. In addition to determining the real-time newborn prevalence of SCD and trait in The Gambia for the first time, this pilot study showed that SCD-POCT is feasible in Gambian health facilities.

Strategies to improve healthcare services for patients with sickle cell disease in Nigeria: The perspectives of stakeholders.

Background: Sickle cell disease (SCD) continues to pose physical and psychosocial burdens to patients, caregivers and health workers. Stakeholder engagement in the processes of policy making and implementation is increasingly becoming the cornerstone of best practices in healthcare. Aim and Objectives: To engage stakeholders with a view to assessing the knowledge of SCD; ascertain the challenges associated with accessibility and affordability of healthcare services; improve the quality of care, and thereby effect behavioral change through increasing attendance and follow-up of patients in the clinics. Methodology: A Stakeholders' Engagement meeting organized by the Sickle Pan Africa Research Consortium Nigeria Network (SPARC-NEt) was attended by patients, caregivers and members of patient support groups, healthcare providers and management/policymakers. The engagement was through PowerPoint presentations, structured questionnaires and an interactive session. The structured questionnaire assessed the knowledge of stakeholders about SCD; the quality of healthcare services; challenges with access and affordability; and SCD-related government policies. Results: Three hundred and twelve stakeholders attended the engagement meeting. Of the 133 that participated in the study, medical workers were the most represented. The majority had good knowledge of what causes SCD (96.2%) and the best place to get help during SCD crisis (98.5%). However, knowledge of the specific preventive measures of SCD and its crisis was not optimal. In terms of the role of community engagement and education, only about one-quarter of the study participants, 34 (25.6%) knew about their positive role in reducing the prevalence of SCD and alleviating SCD crises. Challenges identified include inadequate healthcare personnel and facilities, delay in obtaining laboratory results, long waiting time in the clinic, poor communication, absence of holistic consultation, uncoordinated healthcare services, high cost of care, ignorance, non-prioritization of SCD by government, lack of multisectoral collaboration and partnership with NGOs and international organizations. Strategies proffered to improve healthcare services include, community/stakeholder engagement and health education, sickle cell daycare services, access to a willing and dedicated multidisciplinary workforce, collaboration with support groups and government policies and programs. Conclusion: There is need for regular stakeholder engagement to improve access to healthcare services for SCD patients in Nigeria.

HemoTypeSC point-of-care testing shows high sensitivity with alkaline cellulose acetate hemoglobin electrophoresis for screening hemoglobin SS and SC genotypes

ABSTRACT Introduction: By providing timely actionable results for prompt management, point-of-care testing (POCT) kits have revolutionised medical care for various diseases, ranging from infectious diseases like malaria to genetic disorders, such as sickle cell disease (SCD). They are, however, underutilised in the diagnosis of SCD in developing countries, where the need is greatest. Objective: The study was aimed at assessing the sensitivity of HemoTypeSC POCT among a cohort of children with SCD, previously diagnosed by Alkaline cellulose acetate hemoglobin electrophoresis (ACAE), with or without high-performance liquid chromatography (HPLC). Methods: In this descriptive cross-sectional study, HemoTypeSC test was conducted on all participants and its sensitivity was determined by comparing results with those obtained using ACAE. Discordance was verified with HPLC. Results: One hundred and forty-five children aged one to 19 years were studied. There were 84 males and 61 females (male: female ratio = 1.4:1). The HemoTypeSC was able to correctly diagnose sickle cell anemia (SCA) and hemoglobin SC in all (100%) of the children tested. Conclusion: The HemoTypeSC shows high sensitivity in detecting SCA and hemoglobin SC. Hence, it is useful for targeted screening of individuals suspected of having SCD, leading to rapid diagnosis of these hemoglobinopathies, even in resource-constrained settings.

HemoTypeSC point-of-care testing shows high sensitivity with alkaline cellulose acetate hemoglobin electrophoresis for screening hemoglobin SS and SC genotypes.

INTRODUCTION: By providing timely actionable results for prompt management, point-of-care testing (POCT) kits have revolutionised medical care for various diseases, ranging from infectious diseases like malaria to genetic disorders, such as sickle cell disease (SCD). They are, however, underutilised in the diagnosis of SCD in developing countries, where the need is greatest. OBJECTIVE: The study was aimed at assessing the sensitivity of HemoTypeSC POCT among a cohort of children with SCD, previously diagnosed by Alkaline cellulose acetate hemoglobin electrophoresis (ACAE), with or without high-performance liquid chromatography (HPLC). METHODS: In this descriptive cross-sectional study, HemoTypeSC test was conducted on all participants and its sensitivity was determined by comparing results with those obtained using ACAE. Discordance was verified with HPLC. RESULTS: One hundred and forty-five children aged one to 19 years were studied. There were 84 males and 61 females (male: female ratio = 1.4: 1). The HemoTypeSC was able to correctly diagnose sickle cell anemia (SCA) and hemoglobin SC in all (100%) of the children tested. CONCLUSION: The HemoTypeSC shows high sensitivity in detecting SCA and hemoglobin SC. Hence, it is useful for targeted screening of individuals suspected of having SCD, leading to rapid diagnosis of these hemoglobinopathies, even in resource-constrained settings.

Acute chest syndrome in sickle cell anaemia: higher serum levels of interleukin-8 and highly sensitive C-reactive proteins are associated with impaired lung function.

BACKGROUND: Sickle cell anaemia (SCA) is a chronic inflammatory disorder with multiple organ manifestations including acute and long-term pulmonary dysfunction. AIMS/OBJECTIVES: To assess lung function of children with SCA and determine the possible role of acute chest syndrome (ACS), serum inflammatory cytokines, highly sensitive C-reactive protein (hs-CRP), leucocytes and 25-hydroxyvitamin D on the development of impaired lung function. SUBJECTS AND METHODS: Lung function of 76 children with SCA was determined by spirometer and classified into normal or impaired. Sociodemographic, clinical, haematological, biochemical and immunological data of the two groups were compared by univariate and multivariate analyses. RESULTS: Fifty (65.8%) patients had impaired lung function, comprising of 30.3%, 3.9% and 31.6% with restrictive, obstructive and mixed disease patterns, respectively. Children with previous ACS were 3.6 times more likely to have impaired lung function than those without ACS (82.1% vs 56.3%, p = 0.02, OR 3.6, 95% CI 1.2-10.8). Interleukin (IL)-8 and hs-CRP were significantly higher in patients with impaired lung function (p = 0.02 and <0.001, respectively). Using logistic regression, previous ACS (OR 5.8, 95% CI 1.1-5.8, p = 0.03) and higher serum IL-8 levels (OR 3.0, 95% CI 1.0-8.0, p = 0.02) independently predicted the presence of abnormal lung function. CONCLUSIONS: Lung dysfunction, predominantly restrictive pattern, is common in SCA and is associated with previous ACS and alterations in immunological markers, especially serum IL-8 and hs-CRP. ABBREVIATIONS: ACS: acute chest syndrome; CBT: chronic blood transfusion; ELISA: enzyme-linked immunosorbent assay; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; HPLC: high-density liquid chromatography; hs-CRP: highly sensitive C-reactive proteins; HU: hydroxyurea; IL: Interleukin; PEFR: peak expiratory flow rate; SEM: standard error of the mean; TLC: total lung capacity; 25-OHD: 25-hydroxyvitamin D; VOC: vaso-occlusive crisis; WGH: Wesley Guild Hospital.

Cerebral Vasoreactivity in Children with Sickle Cell Disease: A Transcranial Doppler Study.

BACKGROUND: Impairment of vasodilatory capacity reflecting reduced cerebrovascular reserve was previously shown in adults with sickle cell disease (SCD) and might play a role in the pathophysiology of stroke in such patients. We examined the hypothesis that children with SCD would also have a higher frequency of impaired cerebral vasoreactivity when compared with healthy age- and gender-matched controls. METHODS: Patients were recruited from our hematology outpatient clinic. All SCD patients aged 10-18 years without a history of symptomatic stroke as well as age- and gender-matched healthy children were evaluated with transcranial Doppler (TCD) ultrasonography, with breath-holding maneuver. Breath-holding index (BHI) was calculated by dividing the percentage increase in mean flow velocity occurring during breath holding by the length of time subjects hold their breath after a normal inspiration. BHI was considered abnormal if less than .69. RESULTS: TCD was performed in 42 patients (mean age 12.7 ± 2.2 years) and 20 controls (mean age 13.90 ± 3.04 years). Blood flow velocities were higher in patients with SCD than in controls in all arteries evaluated (P < .001). BHI values in patients with SCD were significantly lower than in control subjects (1.27 ± .65 versus 1.74 ± .15, P = .013 on the left and 1.16 ± .45 versus 1.61 ± .11, P = .002 on the right). BHI was abnormal in 19% of the patients and in none of the controls, P = .036. CONCLUSIONS: Children with SCD may have impaired cerebral vasoreactivity, with low BHI values suggesting a reduced autoregulation capacity.

Changes in Transcranial Doppler Flow Velocities in Children with Sickle Cell Disease: The Impact of Hydroxyurea Therapy.

BACKGROUND AND OBJECTIVES: Hydroxyurea (HU) was recently described as a substitute for chronic transfusion for children with sickle cell disease (SCD) and abnormal transcranial Doppler (TCD) velocities who have received at least 1 year of transfusions. However, the role of HU in reverting elevated TCD velocities in patients not treated with transfusion is still debatable. The objective of the study was to examine whether HU influences the progression of TCD velocities in children with SCD. PATIENTS AND METHODS: Children with SCD with at least 2 TCDs not less than 6 months apart were evaluated over 51 months. Time-averaged maximum mean (TAMM) velocities for the initial and the last transcranial Doppler examinations were noted and differences compared between HU and HU-naive groups. RESULTS: Overall, 68.8% of the HU-group with elevated TCD velocities compared with 40.0% of the HU-naive experienced TCD reversal (P = .047). A higher proportion of the HU-naive group, 7 (14.3%) versus 9.8% of the HU group experienced TCD conversion. Those with initial conditional velocities in the HU-group experienced a significant reduction in TAMM velocities (from 176.8 ± 5.3 to 162.7 ± 13.9 cm/s, difference of 14.1 cm/s; P = .001) unlike those in the HU-naive group (176.3 ± 5.3 to 170.0 ± 18.6 cm/s, difference of 6.3 cm/s; P = .148). The change in the TAMM velocities was also significantly higher among the HU-group (14.1 ± 12.4 cm/s versus 6.3 ± 18.5 cm/s, P = .015). CONCLUSION: Our data suggest a beneficial role of HU in TCD velocity reduction in patients not treated with chronic transfusions, particularly among those with initial conditional TCD velocities.

Low serum vitamin A is prevalent in underfive children with severe malaria and is associated with increased risk of death.

INTRODUCTION: Micronutrient deficiencies are prevalent in developing countries and may influence vulnerability to diseases particularly malaria and its severity. This study investigated serum vitamin A profile of under-five children with severe malaria (SM) in South-western, Nigeria and to determine its association with degree of malaria parasitaemia, types of SM and eventual outcome. METHODOLOGY: Using HPLC, serum vitamin A concentrations of 170 under-five children with SM and 170 age- and gender-matched controls were determined. Parasite species identification and density were also determined. Association between serum vitamin A levels and the degree of parasitaemia, type of SM and patients' outcome were examined by both bivariate and logistic regression analyses. RESULTS: Thirty-five (20.6%) of the children with SM compared with 3 (1.8%) of the controls had hypovitaminosis A, p <0.001, OR = 14.4, 95% Confidence Interval = 4.4 - 47.8. The mean serum vitamin A concentration was also lower in the patients (45.23µg/dL vs. 87.28µg/dL; p <0.001). There was inverse correlation between serum vitamin A levels and malaria parasite density (r = - 0.103, p = 0.027). Higher proportions of children with SM and hypovitaminosis A presented with metabolic acidosis and cerebral malaria (p <0.001 and 0.032 respectively). Children with SM and hypovitaminosis A were 9.1 times more likely to die compared to those without low serum vitamin A levels, OR = 9.1, 95% Confidence Interval = 2.2-38.1, p = 0.002. CONCLUSION: Children with SM had reduced serum vitamin A and significantly contributed to increased morbidity and mortality.

Relationship between serum 25-hydroxyvitamin D and inflammatory cytokines in paediatric sickle cell disease.

BACKGROUND: Alteration in the concentration of inflammatory cytokines may contribute to pathogenesis in sickle cell anaemia (SCA). Vitamin D may suppress pro-inflammatory cytokines and enhance anti-inflammatory cytokines. OBJECTIVE: To compare steady state levels of pro-and anti-inflammatory cytokines of Nigerian SCA children with age- and sex-matched healthy controls, and determine the relationship with 25-hydroxyvitamin-D (25-OHD). Effects of three months of vitamin D supplementation on cytokines of SCA children with suboptimal 25-OHD were also evaluated. METHODS: Serum 25-OHD, IL-1ß, 2, 6, 8, 11, 12, 13, 17, 18 of 95 SCA children and 75 matched controls were determined using HPLC. The 12 SCA children with suboptimal 25-OHD received 2000IU of vitamin D daily for 3months, and their post supplementation cytokines and 25-OHD levels were compared with the baseline values. RESULTS: IL-2, 6, 8, 12, 17 and 18 were higher in SCA children than the controls (p≤0.001), but no significant variation in IL-11 and 13 (p=0.131 and 0.057 respectively). Patients with suboptimal serum 25-OHD had higher IL-6, 8 and 18 (p=0.003, 0.010 and 0.002 respectively) and lower levels of IL-11 (p=0.005). Significant positive treatment effects were observed: post-supplementation, serum 25-OHD increased by 23.3ng/mL, p<0.001; proinflammatory cytokines IL-2, 6, 8, 17 and 18 (p<0.001) were reduced and anti-inflammatory cytokine IL-11 was increased, p<0.001. CONCLUSIONS: Suboptimal 25OHD is associated with enhanced levels of pro-inflammatory markers in children with SCA. Three months of daily vitamin D supplementation reversed the trend. Hence; Vitamin D supplementation may reduce the inflammatory milieu and serve as an anti-inflammatory agent in the management of SCA.

Influence of serum 25-hydroxyvitamin D on the rate of pain episodes in Nigerian children with sickle cell anaemia.

BACKGROUND: In sickle cell disease (SCD), symptoms of vitamin D deficiency (VDD) and chronic pain can overlap. AIM: To examine the relationship between serum vitamin D levels and the frequency of acute pain episodes. METHODS: In this cross-sectional study, serum 25-hydroxyvitamin D (25-OHD) was assayed by high-performance liquid chromatography, and its influence on the number of significant pain episodes was examined by bivariate and logistic regression analyses. RESULTS: The mean (SD) serum 25-OHD level in 123 children with SCD (HbSS) was 105.8 (24.1) nmol/L (range 37.5-155.8). Fourteen patients (11.4%) either had a deficient (1.6%) or insufficient (9.8%) level. None had severe VDD. All the children with sub-optimal vitamin D experienced pain, as did 69.7% of those with normal vitamin D [14 (100%) vs 76 (69.7%), 95% CI 0.7-0.9, p = 0.04]. The mean serum vitamin D level in the 90 patients with at least one pain episode [103.1 (25.2) nmol/L] was significantly lower than the 113.1 (19.3) nmol/L in the 33 without a pain episode (95% CI 1.3-7.8, p = 0.04). The frequency of pain correlated inversely with the serum 25-OHD level. Serum levels of vitamin D (OR 1.2, 95% CI 1.3-1.7, p = 0.04) and fetal haemoglobin concentration (OR 1.6, 95% CI 1.1-1.4, p = 0.02) predicted significant pain episodes. CONCLUSION: In children with SCD, there is a possible association between depressed serum vitamin D levels and increased frequency of acute pain episodes. Vitamin D supplements should be considered in patients with low levels and frequent episodes of pain.

Patients with sickle cell disease are frequently excluded from the benefits of transcranial doppler screening for the risk of stroke despite extensive and compelling evidence.

METHODS:: Transcranial doppler was performed in accordance with the Stroke Prevention Trial in Sickle Cell Anemia Protocol. RESULTS:: Of the 396 patients, 69.5% had homozygous SS hemoglobin. The TCD result was abnormal in 4.8%, conditional in 12.6%, inadequate in 4.3% and abnormally low in 1% of patients. The highest mean flow velocities were 121±23.83cm/s and 124±27.21cm/s in the left and right middle cerebral artery respectively. A total of 28.8% patients (mean age 9.19±5.92 years) were evaluated with TCD for the first time. CONCLUSIONS:: The SCD patients were evaluated with TCD at an older age, representing an important missed opportunity for stroke prevention. Since TCD screening in patients with SCD is important to detect those at high risk for stroke, it is recommended that this screening should be made more readily available.

Patients with sickle cell disease are frequently excluded from the benefits of transcranial doppler screening for the risk of stroke despite extensive and compelling evidence / Pacientes com doença falciforme são frequentemente excluídos dos benefícios do screening com doppler transcraniano para avaliação do risco de acidente vascular cerebral, apesar de evidência extensa e convincente

ABSTRACT Transcranial doppler (TCD) is a strategic component of primary stroke prevention in children with sickle cell disease (SCD). This study was conducted to examine the TCD characteristics of children with SCD in nine different medical centers in Brazil. Methods: Transcranial doppler was performed in accordance with the Stroke Prevention Trial in Sickle Cell Anemia Protocol. Results: Of the 396 patients, 69.5% had homozygous SS hemoglobin. The TCD result was abnormal in 4.8%, conditional in 12.6%, inadequate in 4.3% and abnormally low in 1% of patients. The highest mean flow velocities were 121±23.83cm/s and 124±27.21cm/s in the left and right middle cerebral artery respectively. A total of 28.8% patients (mean age 9.19±5.92 years) were evaluated with TCD for the first time. Conclusions: The SCD patients were evaluated with TCD at an older age, representing an important missed opportunity for stroke prevention. Since TCD screening in patients with SCD is important to detect those at high risk for stroke, it is recommended that this screening should be made more readily available.

RESUMO Doppler transcraniano (DTC) é um componente estratégico da prevenção primária do acidente vascular cerebral (AVC) em crianças com doença falciforme (DF). Este estudo foi realizado para examinar as características do DTC de crianças com DF em nove centros médicos diferentes no Brasil. Métodos: DTC foi realizado de acordo com o protocolo de Stroke Prevention Trial in Sickle Cell Anemia Protocol (STOP). Resultados: Dos 396 pacientes avaliados, 69,5% eram homozigotos para hemoglobina SS. DTC foi anormal em 4,8%, condicional em 12,6%, inadequado em 5,3% e anormalmente baixo em 1%. As máximas velocidades de fluxo médio foram 121 ± 23,83cm/s e 124 ± 27,21 cm/s nas artérias cerebrais media esquerda e direita, respectivamente. Um total de 28,8% dos pacientes (média de 9,19 ± 5,92 anos) foram avaliados com o DTC pela primeira vez. Conclusões: Pacientes com DF foram avaliados com DTC numa idade considerada avançada, o que representa uma importante oportunidade perdida para a prevenção de AVC nessa população. Uma vez que a triagem com DTC em pacientes com DF é essencial para detectar aqueles com alto risco de AVC, recomenda-se que essa triagem seja amplamente disponível no país.

Relationship between foetal haemoglobin and haematological indices in children with sickle cell anaemia from South Western Nigeria.

BACKGROUND: Foetal haemoglobin (HbF, α2γ2) retards polymerisation of haemoglobin (Hb) in sickle cell anaemia (SCA). In Nigeria, studies on the levels of HbF and its relationship with haematological indices are scanty. This study evaluated HbF concentrations of children with SCA from Southwestern Nigeria and correlated the levels with various haematological indices. MATERIALS AND METHODS: HbF levels were quantified by high-performance liquid chromatography and haematological parameters determined with automated haemoanalyser. The relationship between steady-state HbF levels and blood parameters were assessed by statistical analyses. RESULTS: The mean HbF of the 91 children with SCA (9.6% ± 5.9%) was significantly higher than 0.5 ± 0.7% for the 91 age- and sex-matched controls, P < 0.001. About two-third of children with SCA, sixty (65.9%) had low HbF levels (HbF of < 10%) whereas about one-third, 31 (34.1%) had high HbF level (HbF of ≥ 10%). The mean Hb concentration, haematocrit (Hct) and total red blood cell count were significantly lower amongst children with SCA, whereas the total white blood cell (WBC) counts, neutrophils, monocyte and lymphocyte percent, platelet counts, mean corpuscular Hb (MCH) and MCH concentration were significantly higher. HbF had a positive but weak correlation with Hct (r = 0.24, P = 0.014), Hb concentration (r = 0.21, P = 0.047) and red cell distribution width (r = 0.25, P = 0.015) and an inverse correlation with WBC count (r = -0.23, P = 0.038). CONCLUSION: Children with SCA had higher levels of HbF than matched controls. HbF had an inverse correlation with the WBC count and direct relationship with Hct and Hb concentration. It is recommended that routine determination of HbF and its induction are essential to maintain optimal haematological state of patients with SCD.

Posterior Circulation Evaluation in Patients with Sickle Cell Anemia.

BACKGROUND: The role of transcranial Doppler (TCD) ultrasonography in identifying children with sickle cell anemia (SCA) at risk for stroke is well known; however, the major studies that evaluated TCD velocities in children with SCA did not report posterior circulation evaluation data. The objective of our study was to describe the pattern of blood flow velocities in the posterior circulation of patients with SCA and to examine their relationship with findings on magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA). METHODS: All adult patients with SCA followed in the outpatient clinic of our hospital were evaluated with TCD and MRI/MRA. The highest velocities of the middle cerebral arteries or internal carotid arteries were taken as the time-averaged maximum mean (TAMM) velocity for each patient and the maximum mean flow velocities in the posterior circulation (TAMMpost) were recorded. RESULTS: Fifty-six patients with SCA and 56 healthy nonanemic volunteers were evaluated. The mean TAMMpost in the basilar, vertebral, and posterior cerebral arteries (PCAs) were significantly higher among cases than controls (P < .01). In patients with SCA, the TAMMpost in all posterior circulation arteries had a positive correlation with TAMM. Only 1 patient with stenosis in the posterior circulation (right PCA) was identified. CONCLUSION: We found a low frequency of stenosis but high blood flow velocities in the posterior circulation in patients with SCA. The role of increased TCD velocities in the posterior circulation upon stroke risk in patients with SCA should be further examined.

Electrocardiographic abnormalities and dyslipidaemic syndrome in children with sickle cell anaemia.

BACKGROUND: Lipid and electrocardiographic (ECG) abnormalities have been reported in adults with sickle cell anaemia (SCA) and may reflect underlying structural and/or functional damage. However, the relationship between ECG and lipid abnormalities among children with sickle cell disease is not fully understood. OBJECTIVES: To compare the steady-state lipid and ECG abnormalities in children with SCA to the controls and examine the hypothesis that lipid abnormalities are closely related to electrocardiographic abnormalities, and therefore are a reflection of cardiac damage among these children. METHODS: Clinical, laboratory and ECG profiles of 62 children with SCA and 40 age- and gender-matched haemoglobin AA controls were compared. The influence of clinical characteristics, lipids profiles, markers of haemolysis, and renal and hepatic dysfunction on ECG pattern in children with SCA was then determined. RESULTS: The patients had lower average diastolic and mean arterial blood pressure, total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels than the controls, (p = 0.001, 0.002, 0.000 and 0.000, respectively). The mean triglyceride level was significantly higher (p < 0.001), while high-density lipoprotein cholesterol (HDL-C) levels were comparable (p = 0.858). The cases were about six times more likely to have left ventricular hypertrophy than the controls (OR = 6.4, 95% CI = 2.7-15.6, p = 0.000). Haematocrit level had a negative correlation with QTC (r = -0.3, p = 0.016) and QT intervals (r = - 0.3, p = 0.044). Triglyceride levels had a positive correlation with the PR interval (r = 0.3, p = 0.012), while serum alanine transferase (ALT) concentrations had an inverse correlation with PR interval (r = -0.3, p = 0.015). There was no statistical difference in the sociodemographic and clinical characteristics of the SCA children with or without ECG abnormalities. However, the mean triglyceride and serum ALT levels in those with ECG abnormalities were significantly higher than those without (p = 0.007 and 0.045, respectively). CONCLUSION: Lipid and ECG abnormalities are common in children with SCA. Elevated triglyceride and serum ALT levels are possible biochemical markers of ECG abnormalities in these patients.

Haptoglobin gene polymorphisms and interleukin-6 and -8 levels in patients with sickle cell anemia

BACKGROUND: Haptoglobin genotypes, and interleukin-6 and -8 participate in the pathophysiology of sickle cell anemia. The expression of cytokines is regulated by genetic mechanisms however the effect of haptoglobin polymorphisms on these cytokines is not fully understood. This study aimed to compare the frequency of haptoglobin genotypes and the interleukin-6 and -8 concentrations in sickle cell anemia patients and controls to investigate the association between haptoglobin genotypes and cytokine levels.METHODS: Sixty sickle cell anemia patients and 74 healthy individuals were analyzed. Haptoglobin genotypes were determined by multiplex polymerase chain reaction, and the interleukin-6 and -8 levels by enzyme linked immunosorbent assay. The association between haptoglobin genotypes and cytokines was investigated by statistical tests.RESULTS:Hp2-1 was the most common genotype in both the cases and controls while Hp1-1 was less frequent among sickle cell anemia patients. Interleukin-6 and -8 levels were higher in patients than controls (p-value <0.0001). There was no significant difference in interleukin-6 and -8 concentrations between the genotypes (p-value >0.05). A similar trend was observed among the controls.CONCLUSION: Although, levels of interleukin-6 and -8 were higher in the sickle cell anemia patients, they appeared not to be related to the haptoglobin genotypes. Further investigations are necessary to identify factors responsible for increased secretion of the interleukin-6 and -8 pro-inflammatory cytokines in patients with sickle cell anemia.

Haptoglobin gene polymorphisms and interleukin-6 and -8 levels in patients with sickle cell anemia.

BACKGROUND: Haptoglobin genotypes, and interleukin-6 and -8 participate in the pathophysiology of sickle cell anemia. The expression of cytokines is regulated by genetic mechanisms however the effect of haptoglobin polymorphisms on these cytokines is not fully understood. This study aimed to compare the frequency of haptoglobin genotypes and the interleukin-6 and -8 concentrations in sickle cell anemia patients and controls to investigate the association between haptoglobin genotypes and cytokine levels. METHODS: Sixty sickle cell anemia patients and 74 healthy individuals were analyzed. Haptoglobin genotypes were determined by multiplex polymerase chain reaction, and the interleukin-6 and -8 levels by enzyme linked immunosorbent assay. The association between haptoglobin genotypes and cytokines was investigated by statistical tests. RESULTS: Hp2-1 was the most common genotype in both the cases and controls while Hp1-1 was less frequent among sickle cell anemia patients. Interleukin-6 and -8 levels were higher in patients than controls (p-value <0.0001). There was no significant difference in interleukin-6 and -8 concentrations between the genotypes (p-value >0.05). A similar trend was observed among the controls. CONCLUSION: Although, levels of interleukin-6 and -8 were higher in the sickle cell anemia patients, they appeared not to be related to the haptoglobin genotypes. Further investigations are necessary to identify factors responsible for increased secretion of the interleukin-6 and -8 pro-inflammatory cytokines in patients with sickle cell anemia.