Clinical profile of paediatric sickle cell disease at a reference hospital in North–eastern Nigeria

Background: Sickle cell disorders (SCD) are the commonest inherited haemoglobin (Hb) disorders. Globally, about 300,000 babies are born annually with these conditions. The clinical profiles of SCD have been described in many parts of the world. These however have not been adequately investigated in some parts of Nigeria. This study evaluated the clinical features, Hb phenotype and complications of children with SCD being managed at a Paediatric haematology clinic in Northern Nigeria. Methods: A prospective observational study of steady state SCD patients aged 2 – 16 years, was conducted from January, 2019 -October, 2020. Historical and examination findings were documented. Analysis of data was done with the Statistical Package for Social Sciences (SPSS) version 20.0. Results: One hundred children were studied. Mean age was 6.97 ± 3.63 years. Male: female ratio was 1.6:1.Mean weight and mean height were lower than reference standards (t= -1.20, p= 0.14), (t= - 0.66, p= 0.27) respectively. Mean age at diagnosis was 13.24 ±14.83 months, and at first presentation was 13.86 ±17.51 months, 58.5% of subjects were adequately vaccinated for age, while 92% had a Hb phenotype of SS. Acute chest syndrome occurred more frequently in children aged 9-12 years (χ2= 11.59, P ˂ 0.001), and in those with severe bacterial infections (χ2= 7.41, p= 0.006). Conclusion: The complications of Paediatric SCD in this part of North-Eastern Nigeria mirrors those in other parts of the country. Socio-economic class, Hb phenotype and vaccination status had no influence on the development of complications.

Prevalence of sickle cell disorders and malaria infection in children aged 1–12 years in the Volta Region, Ghana: a community-based study

Background Alterations in the structure of haemoglobin (Hb) are usually brought about by point mutations affecting one or, in some cases, two codons encoding amino acids of the globin chains. One in three Ghanaians are said to have sickle cell disorders, whereas malaria continues to be one of the leading causes of mortality among children. This study determined the prevalence of sickle cell disorders and malaria infection among children aged 1–12 years in the Volta Region. Methods This was a community-based cross-sectional survey that involved 938 children aged 1–12 years selected from three districts, one each from the 3 geographical zones of the Volta Region using a multistage sampling method. Demographic information was collected using a standard questionnaire and anthropometric indices were measured. Isoelectric focusing (IEF) electrophoresis was used to determine the Hb genotypes and sub-microscopic parasites were determined by PCR. Results The prevalence of sickling screening positive was 16.0% with an overall prevalence of sickle cell disorders being 2.0%. Among the individual genotypes making up the sickle cell disorders, genotype HbSF was the highest (0.9% as compared to 0.2%; HbSS, 0.6%; HbSC and 0.3%; HbSCF). Microscopic Plasmodium falciparum parasitaemia was detected among 5.5% of the children and 14.2% sub-microscopic prevalence by PCR. Children with sickle cell disorders were more likely to have sub-microscopic parasitaemia (AOR = 5.51 95%CI (2.15, 14.10), p < 0.001) as well as anaemia (AOR = 3.03 95% CI (1.04, 8.82), p = 0.042), compared to those with normal genotypes. There was no significant difference observed between sickle cell disorders and growth and development of the children screened. Conclusions Sickle cell disorders were significantly associated with sub-microscopic parasitaemia as well as anaemia in this study. Establishment of sickle cell clinics in the district and regional hospitals will help in the management of children with the disorder and also generate a national database on sickle cell disorders. National neonatal screening policies must also be put in place to help in early detection and management of these disorders.

Outcomes of Sickle Cell Disorders in COVID-19 Infection: An Institutional Experience

Introduction: With the emergence of the Coronavirus Disease 2019 (COVID-19) as a global pandemic came the concern that it would adversely affect individuals with comorbid conditions. In sickle cell disease (SCD), the apprehension was largely driven by concerns that the disease causes chronic inflammation, organ dysfunction and a prothrombotic state, especially during a vaso-occlusive crisis. Our assumption and hypothesis was that SCD pathology would be exacerbated by SARS CoV-2 infection leading to higher rates of acute chest syndrome (ACS), venous thromboembolism (VTE), more robust inflammatory responses requiring ICU care and increased death rates. Sickle cell trait (SCT) is frequently perceived as a benign condition; however, mounting evidence has shown that severe hypoxia (such as that seen in COVID-19 infection) can trigger sickle-related complication such as VTE, papillary necrosis and splenic infarcts and, in rare cases, ACS. In this retrospective analysis, we aimed to determine if sickle cell disorders (SCD & SCT) would confer poorer outcomes and/or increased mortality due to COVID-19 infection. Methods: Within the MedStar health care system there are 7,551 adult patients with a diagnosis of sickle cell disorder. We performed a retrospective chart review of all patients in the MedStar system with hemoglobinopathy and a lab-verified diagnosis of COVID-19 infection between March 1, 2020 and June 30, 2020. Sixty-one patients met our search criteria with 21 patients admitted to the hospital and 40 patients managed in the outpatient setting. Of the 21 patients admitted: 9 patients had sickle cell disease (Hb SS, Hb SC, Hb SB thalassemia) and 11 patients had sickle cell trait. One patient had HbC disease. Results: Results were analyzed by SCD genotype (Hb SS, Hb SC, Hb SB Thalassemia) versus the presence of a SCT. Due to the small sample size, statistical significance was not met in the variables. In the 21-patient cohort: 76.2% were female (60% of SCD and 90.9% of SCT) and 100% were African American. Median age was 46.5 years in the SCD group and 38 years in the SCT group. Length of stay was 10 days in the SCD group and 6 days in the SCT group. Mean peak white blood cell count and platelet count were significantly higher in SCD group (WBC: 15.1 k/uL vs 7.5 k/uL; p value 0.099. Platelets: 523 k/uL vs 185 k/uL; p value 0.082). Inflammatory markers were more elevated in the SCD cohort: mean Ferritin (915 ng/mL vs 520 ng/mL), mean D Dimer (2.96 mg/L vs 1.07 mg/L) and mean LDH (543 units/L vs 392 units/L). However, mean peak C-reactive protein (CRP) was higher in the SCT group (117.5 mg/L vs 67.7 mg/L). Admission to the intensive care unit (ICU) occurred in 11.1% with SCD & 36.4% with SCT and renal replacement therapy was required in 11.1% with SCD & 28.6% with SCT. Nasal cannula was required in 75% of patients (88.9% of SCD & 57.1% of SCT; p value 0.262) with only one SCT patient requiring intubation and mechanical ventilation whom later died. Two patients with Hb SS developed ACS, one of whom died. One patient with HbSC disease developed ACS and an acute cerebrovascular accident. No VTE or pulmonary embolisms were documented in this cohort. Therapeutic drugs used in the cohort varied, with 43.8% receiving antibiotics (other than Azithromycin), 37.5% receiving Azithromycin and 25% receiving Hydroxychloroquine. None of the patients received convalescent plasma, steroids, tociluzumab, sarilumab or remdesivir. Anticoagulation was used in 93.8% of the patients (13.3% of which were in therapeutic doses). Conclusions: Sickle cell disease diagnosis did not seem to influence response to COVID19 illness when compared to age-matched individuals with SCT. The number of patients with sickle cell disease admitted to the hospital after contracting SAR CoV2 infection was also remarkably low. These findings were, in general, unexpected. Although the inflammatory biomarkers were generally higher in the patients with SCD, more patients with SCT were admitted to the ICU and required renal replacement therapy. The major drawbacks of the study are the small sample size and missing data points (lack of labs, lack of documentation, transfer to another facility) that did not allow us to draw statistical conclusions about the differences in the patients with SCD versus SCT. We were also unable to determine the influence of SCD severity and pre-existing organ complications on outcomes in COVID 19 disease. Additional studies with larger cohorts is warranted. Disclosures No relevant conflicts of interest to declare.

Pattern of Sickle Cell Disorders: A Study from a Tertiary Care Center in Eastern Part of India

Introduction:Sickle cell disorders were originally found in the African regions, Arabian Peninsula and parts of India. However, in today's age of globalization patients with homozygous or compound heterozygous Sickle cell disorders can be found all over the world. The objective of our study was to assess the distribution and clinical presentation of patients with Sickle homozygous or heterozygous diseases in the Eastern part of India. Methods:Patients who attended the Thalassemia Clinic in our tertiary care center, between 1st January 2018 to 31st May 2020 (2 years and 4 months) were retrospectively analysed and the ones with a component of Sickle haemoglobin(HbS), either in the form of Sickle cell anemia/homozygous Sickle cell disorders(SCA) or compound heterozygous diseases, like Sickle cell/β thalassemia(HbS/β), Sickle cell/Delta thalassemia(HbS/D), Sickle cell Haemoglobin/E thalassemia(HbS/E), were included in the study. People having Sickle cell trait (HbS trait), have also been included. Thorough history of painful crises, blood transfusions, family history and treatment history was elicited and every patient was clinically examined. The patients were diagnosed by High Pressure Liquid Chromatography (HPLC) or Thalassemia Mutation analysis by Polymerase Chain reaction (PCR). Results:A total of 95 patients with a component of HbS were considered as our study cohort, with HbS/β thalassemia patients being the majority (53.7%), followed by SCA (30.5%). Age of the study cohort ranged between 2-50 years age. HbS/β thalassemia patients presented at a later age (median 17.5 years) than SCA patients (median 12 years). Their demographic distribution is depicted in Table 1. The most common clinical presentation was painful crisis (32,33.7%), be it abdominal pain (11,11.6%) or bone pain (13,13.7%). Other presenting complaints were pallor (26,27.4%), jaundice (12,12.6%) and fever (4,4.2%). Some rarer presenting manifestations were fatigue (4,4.2%), splenic infarction (1,1%), convulsions (1,1%), Raynaud's phenomenon (1,1%), headache (1,1%) or itchy skin lesions (1,1%). Few patients (4,4.2%) had recurrent pregnancy loss, and one patient was diagnosed incidentally during an antenatal check-up. Most patients had more than one complaint. Very occasionally patients required hospital admission, the reasons being, chest pain, fever, convulsions or abdominal pain. HbS trait was diagnosed incidentally during evaluation for other illnesses, most commonly during evaluation of pallor (3,60%): one patient was later diagnosed with iron deficiency anemia. Most patients who attended our center were from within the state or neighbouring states. The patients were treated with Hydroxyurea, with/without blood transfusions, chelation therapy with Deferasirox as required and Folic acid supplementation. People with HbS Trait continued to receive Folate supplementation. Discussion and Conclusions:This study highlights the varied distribution of HbS among the population attending a tertiary care center, irrespective of a specific area-based population. Till date most studies conducted in India have highlighted the prevalence of Sickle cell disorders among specific focused populations. HbS/β thalassemia was the most common sickle cell disorder in our study. This is in contrast to most findings in published literature from other countries, where SCA is the commonest. Only one other study conducted in eastern India, has depicted a finding similar to ours. The median age of disease presentation was at a later age in our study, in contrast to findings in published literature from other countries. There is a variation in the severity of disease manifestation in our study cohort. The most common painful crisis was bone pain, followed by abdominal pain. Pallor was also one of the commonest presenting symptoms. Stroke, a common manifestation of SCA in other countries, was rare in our study cohort. Disclosures No relevant conflicts of interest to declare.

The Prevalence and Impact of Arrhythmias in Hospitalized Patients with Sickle Cell Disorders: A Large Database Analysis

Introduction: Sickle cell disorders (SCD) is associated with progressive dysfunction of vital organs, including the cardiovascular system. While the development of pulmonary hypertension and left ventricular dysfunction have been previously studied, the burden of arrhythmias in SCD patients remains largely unknown. Thus, we aim to describe and analyze the prevalence and impact of arrhythmias in hospitalized adult patients with SCD and their impact in patient-oriented outcomes. Methods: We identified incident arrhythmias in patients with SCD in the National Inpatient Sample (NIS) database in 2 years (2016-2017), using ICD-10 codes. We compared major patient characteristics, outcomes, and economic impact between groups of SCD patients with and without documented arrhythmias. A logistic regression model was used to control for age, sex, race, admission type, hospital characteristics, and relevant comorbidities. To increase statistical robustness, propensity-score matching for age, sex, income, and comorbidities was used to match 1144 SCD patients with arrhythmia and 1144 patients without. Results: Among inpatients with SCD in the database, 5,930 of 174,450 patients with SCD had documented arrhythmias (3.4%). The arrhythmia group consisted mostly of patients' sickle cell disease (5,650; 95%), while 245 had sickle cell trait, and 35 were classified as having other sickle cell disorders. Individuals in the arrhythmia group were significantly older (mean age 41.3, SD 14.1) than those with no arrhythmia (mean age 31.5, SD 10.3). Further, arrhythmia group had higher prevalence of hypertension (44.2% vs 19.1%, p&lt;0.001), congestive heart failure (25.8% vs 4.1%, p&lt;0.001), chronic kidney disease (24.0% vs 5.6%, p&lt;0.001), valvular heart disease (9.3% vs 1.5%, p&lt;0.001), myocardial infarction (4.1% vs 1.25%, p&lt;0.001), type 2 diabetes mellitus (3.5% vs 1.7%, p&lt;0.001), and pulmonary hypertension (3.5% vs 1.2%, p&lt;0.001). When looking at major outcomes, after adjusting for confounders, arrhythmias were positively associated with all cause in-hospital mortality with an adjusted OR of 53.6 (95% CI 44.3, 65.1). After propensity-matching (Table 1), the arrhythmia group had a higher rate of all-cause in-hospital mortality (6.12% vs 0.35%, p&lt;0.001), higher median length of stay (6.8 days vs 5.8 days, p&lt;0.001), and mean total hospital charges ($13,441 vs $10,255, p&lt;0.001). There was no statistically significant difference in the rate of stroke between both groups. Conclusions: The presence of arrhythmias in patients with SCD was associated with markedly increased all cause in-hospital mortality, even after adjusting for confounders via logistic regression and propensity-score matching analyses. Despite a relatively low overall prevalence of 3.4% among this large inpatient cohort, this data suggests that arrhythmias may confer an important excess disease burden in SCD patients, including higher mortality. Intuitively, arrythmias confer higher mortality in patients with chronic disorders and multiple cardiovascular risks, whether this is specific to SCD deserves further study. Also, studies are needed to better understand the occurrence particularly in relation to active vaso-occlusive crisis and to evaluate whether SCD individuals with arrhythmias could potentially benefit from more intensive monitoring and/or better cardiovascular disease control. Disclosures No relevant conflicts of interest to declare.

Child and adolescent health

This chapter covers health issues and how to manage them. It covers acne, asthma, autistic spectrum disorders, behavioural disorders, birth injuries, problems with the bone and joint, cerebral palsy, cancer in childhood, cleft lip and palate, congenital heart defects and other impairments, constipation and encopresis, cystic fibrosis, deafness, depressive behaviours, eczema, emotional problems, endocrine problems, epilepsy, genetic problems, and growth disorders. It also includes infections and the consequences of infectious diseases in childhood, insects, neural tube defects, nocturnal enuresis, overweight children and adolescents, sickle cell disorders, thalassaemia, sudden infant death syndrome, and vomiting.