Shift in emergency department utilization by frequent attendees with sickle cell disease during the COVID-19 pandemic: A multicentre cohort study.

While the coronavirus disease-2019 (COVID-19) might have increased acute episodes in people living with sickle cell disease (SCD), it may also have changed their reliance on emergency department (ED) services. We assessed the impact of the COVID-19 pandemic and lockdowns on ED visits in adult SCD people followed in five French reference centres, with a special focus on 'high users' (≥10 visits in 2019). We analysed the rate of ED visits from 1 January 2015 to 31 December 2021, using a self-controlled case series. Among 1530 people (17 829 ED visits), we observed a significant reduction in ED visits during and after lockdowns, but the effect vanished over time. Compared to pre-pandemic, incidence rate ratios for ED visits were 0.59 [95% CI 0.52-0.67] for the first lockdown, 0.66 [95% CI 0.58-0.75] for the second and 0.85 [95% CI 0.73-0.99] for the third. High users (4% of people but 33.7% of visits) mainly drove the reductions after the first lockdown. COVID-19 lockdowns were associated with reduced ED visits. While most people returned to their baseline utilization by April 2021, high users had a lasting decrease in ED visits. Understanding the factors driving the drop in ED utilization among high users might inform clinical practice and health policy.

The enigma of sickle cell hepatopathy: Pathophysiology, clinical manifestations and therapy.

Sickle cell disease (SCD) is one of the most common genetic disorders in the world predominantly affecting economically disadvantaged populations. There is a notable discrepancy between the growing adult SCD population and available diagnostic and therapeutic interventions for SCD. Sickle cell hepatopathy (SCH) is an all-inclusive term to describe the acute and chronic liver manifestations of SCD. The pathophysiology of SCH follows no defined pattern or sequence that poses challenges to clinicians and researchers alike. Evidence is lacking for this underreported disease at various levels from diagnostic to therapeutic options. This paper reviews the basic pathophysiology, clinical features, biochemical and radiological findings of various SCH manifestations and outlines the management of each condition. Old and new therapy options in SCD including hydroxyurea, red blood cell exchange transfusion, ursodeoxycholic acid, voxelotor, l-glutamine and crizanlizumab have been reviewed to investigate the role of these options in treating SCH. The role of liver transplant, haematopoietic stem cell transplant and gene therapy in SCH patients have been reviewed.

Persistent albuminuria and chronic kidney disease in adults with sickle cell anaemia: Results from a multicenter natural history study.

Clinical and laboratory correlates of chronic kidney disease (CKD) in sickle cell anaemia remain incompletely defined. In a multicenter cohort study, we evaluated the prevalence of persistent albuminuria (PA) and characteristics associated with PA, albumin-creatinine ratio (ACR) and decreased estimated glomerular filtration rate (eGFR) using logistic, linear and multinomial regression models, respectively. Of 269 participants (median age: 30 years; 57.2% females), the prevalence of PA was 35.7%. Using baseline ACR values of <100 and ≥100 mg/g, the probabilities of PA were 30.0% and 94.6%, respectively. In multivariable logistic regression analyses, male sex (ß = 0.80 [SE = 0.36], p = 0.024) and ACE inhibitors/ARBs use (ß = 1.54 [SE = 0.43], p < 0.001) were associated with higher likelihoods of PA, while higher haemoglobin (ß = -0.33 [SE = 0.13], p = 0.009) and HbF (ß = -0.04 [SE = 0.02], p = 0.041) were associated with lower likelihoods of PA. In multivariable multinomial regression analyses, older age (ß = 0.06 [SE = 0.02], p = 0.004) and higher alkaline phosphatase (ß = 0.01 [SE = 0.00], p = 0.004) were associated with higher odds of having eGFR 60-90 versus eGFR>90 mL/min/1.73 m2 using the cystatin C-based CKD-EPI-2012 equation. Additionally, higher systolic blood pressure (ß = 0.11 [SE = 0.03], p = 0.001) and blood urea nitrogen (ß = 0.45 [SE = 0.12], p < 0.001) were associated with higher odds, while higher haemoglobin (ß = -1.22 [SE = 0.43], p = 0.004) was associated with lower odds of having eGFR<60 versus eGFR>90 mL/min/1.73 m2. PA and decreased eGFR are associated with measures of disease severity and comorbid conditions (Clinicaltrials.gov Identifier: NCT03277547).

Clinical Profile and middle cerebral artery velocity of children with sickle cell anaemia seen in UUTH, Uyo, Akwa Ibom state, Nigeria.

Background: The risk of stroke in individuals with Sickle Cell Anaemia (SCA) can be assessed by routine non-invasive measurement of their cerebral blood flow using a Transcranial Doppler (TCD) ultrasound scan. This study aimed to determine the difference in blood flow velocity parameters in the middle cerebral artery (MCA) of children with sickle cell anaemia compared to a normal age-matched population. Methodology: This was a hospital-based comparative cross-sectional study among 40 SCA patients aged 3-16 years, in steady state and 40 age and sex-matched HbAA healthy subjects. This study lasted from June to October 2019. Medical history was retrieved using a structured questionnaire. The time-averaged mean of maximum velocity (TAMMV) of the right and left MCA was measured using non-imaging TCD. Results: The mean age ± SD of the SCA patients was 9.1 ± 4.4 years. The SCA patients and sex and age-matched HbAA group consisted of 23 (57.5%) males and 17 (42.5%) females respectively. SCA patients had a significantly lower mean ± SD haemoglobin (Hb) than the controls (7.1 ± 1.1g/dl vs 11.1 ± 1.4g/dl; p<0.001). The right MCA of the patients with SCA had a significantly higher mean flow velocity compared to the controls (94.1 ± 23.1 vs 55.0 ± 8.8cm/sec, p<0.001). Conclusion: The mean TAMMV recorded in the SCA subjects were significantly higher than that of the non-SCA subjects. There is a need to ensure that TCD ultrasound is employed as a routine screening tool for stroke risk among SCA patients in Nigerian tertiary health institutions.

Platelet Aggregation Studies and Coagulation Profile in Sickle Cell Disease in Symptomatic and Steady State Patients.

To determine whether there is higher degree of platelet and/ or coagulation activation in sickle cell anaemia (SS) patients in complications and with clinical risk factors. A cross sectional study was conducted at a tertiary health care centre in central India with study groups: sickle cell disease (SCD): sickle cell anaemia (SS) and sickle cell trait (AS) consisting of 100 subjects each and controls (AA) with 40 subjects. Platelet aggregation (PA) with ADP, collagen and epinephrine, PT and aPTT were performed in all subjects and PA with ristocetin in ten candidates of each group. ANOVA and student's unpaired t test were used to compare PA and coagulation profile of the three groups with respect to age groups, gender, present diagnosis, history of complications, frequency of hospital admissions (high ≥ 3/year) and frequency of blood transfusion (high > 2/year). The max PA% with ADP was significantly less in SS patients in steady state, which was even lesser in those having symptoms, complications in past/ present, high-frequency hospital admission and > 2 blood transfusions per year subgroups, as compared to all other groups and subgroups, but not consistently with collagen and epinephrine. The max PA % with ristocetin was least in SS with complications. No statistically significant difference in PT and aPTT values among the various clinical risk subgroups and groups was found. SCD patients can be monitored by using PA with ADP for their timely and better management. PA with ADP, PT and aPTT should be added to the workup of these patients for improved prognostication.

Assessment of hypoxemia among young adults with sickle cell anaemia in steady state in southwestern Nigeria: a crosssectional study.

OBJECTIVES: Hypoxia is a known feature of sickle cell anaemia (SCA) which results from chronic anaemia and recurrent vaso-occlusive crisis (VOC) which can cause tissue ischaemia that leads to an end organ damage. The hallmark of SCA is chronic anaemia and recurrent vaso-occlusive crisis. The aim of this study is to compare the oxygen saturation of sickle cell anaemic individuals with the normal haemoglobin type (Hb AA) control and also to determine the prevalence of hypoxemia among SCA. RESULTS: Two-hundred and twenty-two (136 Hb SS and 86 Hb AA) participated in the study. The mean ± SD of age (years), oxygen saturation (%) and pulse rate (bpm) of participants with sickle cell anaemia and Hb AA control were 21.85 ± 3.04 and 22.14 ± 3.18 (t = 0.701, p = 0.436), 95.21 ± 3.02 and 98.07 ± 0.81 (t=-8.598, p < 0.0001) and 77.10 ± 9.28 and 73.16 ± 8.52 (t = 3.173, p = 0.002) respectively. The prevalence of hypoxemia among SCA participants was 47.1%. Prevalence of hypoxemia in males with SCA was 60.9% while 39.1% of the females had hypoxemia.

Impact of SARS-CoV-2 infection on pain crisis and acute chest syndrome in patients with sickle cell anemia: A retrospective multi-cohort study based on US national data from 2020 to 2022.

COVID-19 infection has been a significant contributor to global morbidity and mortality, especially among those patients with chronic diseases. The Centers for Disease Control and Prevention have classified sickle cell disease (SCD) as a condition that increases the risk of severe illness from COVID-19 infection. A retrospective study was conducted using the TRiNetX health research network database to identify SCA patients ( HbSS, Sbeta-thalassemia zero) who had SARS-CoV-2 infection over 2 years; these were compared with similar patients who did not have the infection in terms of demographics, pain control, and laboratory parameters COVID-19 illness impacts [ain crises and ACS, and prior vaccination against influenza and COVID-19 may represent a protective factor for developing pain crises.

Maximizing longevity: erythropoietin's impact on sickle cell anaemia survival rates.

Sickle cell anaemia (SCA) stands as a hereditary blood disorder characterized by mutated haemoglobin, causing red blood cells to adopt a sickle shape, leading to complications like vaso-occlusive crises, anaemia, and organ damage. Despite advancements in treatment, managing SCA remains challenging, with limited options to increase life expectancy and improve quality of life for affected individuals. This paper reviews the potential impact of erythropoietin (EPO) therapy in enhancing life expectancy and ameliorating complications in individuals with SCA. EPO, primarily recognized for its role in stimulating red blood cell production, holds promise in mitigating anaemia, reducing transfusion dependence, and possibly diminishing the frequency and severity of vaso-occlusive crises in SCA patients. Moreover, by stimulating red blood cell production, EPO therapy might alleviate the vaso-occlusive process, thus reducing the frequency of painful crises and associated complications. Additionally, considering the potential side effects and the need for continuous monitoring, the use of EPO in SCA treatment requires cautious consideration. The potential of EPO therapy in SCA offers a glimpse into novel strategies aimed at improving the quality of life and extending the life expectancy of affected individuals. In conclusion, while the application of EPO in SCA treatment holds promise, additional research is indispensable to comprehend its precise role, optimize dosing strategies, and ensure safety, thereby paving the way for enhanced life expectancy and improved outcomes for individuals living with SCA.

Left ventricular global longitudinal strain and acute myocardial injury in patients with sickle cell disease admitted to the intensive care unit for vaso-occlusive crisis.

In patients with sickle cell disease (SCD), SCD-related cardiomyopathy may be partly due to repeated ischaemic events related to sickling during vaso-occlusive crises, but few clinical studies support this hypothesis. We evaluated the incidence of acute myocardial ischaemia during vaso-occlusive crises as assessed by the left ventricular global longitudinal strain (LVGLS) and high-sensitive cardiac troponin T (hs-cTnT). We included adult patients with SCD admitted to the intensive care unit (ICU) for vaso-occlusive crisis. We collected hs-cTnT and measured LVGLS with echocardiography at admission (day 1), day 2, day 3 and ICU discharge. Among 55 patients included, considering only the first hospitalization of patients admitted several times, 3 (5%) had elevated hs-cTnT at ≥1 time point of the ICU stay. It was ≤2 times the upper limit of normal in two of these patients. LVGLS was altered at ≥1 time point of the ICU stay in 13 (24%) patients. Both hs-cTnT and LVGLS were abnormal at ≥1 time point of the hospital stay in 2 (4%) patients. Acute myocardial injury as assessed by troponin elevation and LVGLS impairment was a rare event during vaso-occlusive crises.

Dental Caries in Children with Sickle Cell Disease and Its Association with the Use of Hydroxyurea and Penicillin Prophylaxis in Dar Es Salaam.

Purpose: This comparative study sets out to report dental caries status among individuals with Sickle Cell Disease (HbSS) against those with sickle cell trait (HbSA) and those without the disease (HbAA) as controls. The study further assessed the impact of penicillin chemoprophylaxis and hydroxyurea use on dental caries among Sickle Cell Disease participants. Methods: This was a comparative cross-sectional study in which 93 children aged 30 to 60 months were recruited. There were 60 participating children who had SCD (HbSS), 17 with SCD trait (HbAS) and 16 were without SCD or SC trait (HbAA). A questionnaire was used to record sociodemographic details including mean age in months and sex and on haemoglobin genotype for all the participants. Specifically, for the participants with HbSS, information on their whether they are taking hydroxyurea (HU), and penicillin chemoprophylaxis was recorded. To assess the prevalence of dental caries, clinical examination of all primary maxillary and mandibular teeth to determine the presence or absence of dental caries lesions was also recorded. Results: A total of 1197 teeth from 93 children were examined, whereby, 45 (2.4%) of them had dental caries. The participating children with HbAA genotype (6.6%, N=21) had more dental caries than their HbSS counterparts (2.0%, N=24), while none of the participants with HbAS exhibited dental caries. Among the participants with HbSS, males and those who use HU were 3.79 and 3.07 times more likely to have dental caries than their counterparts, female and non-users of HU, respectively. Conclusion: Dental caries was observed to be low among participants with HbSS when compared to those with HbAA. More research utilizing more robust methodologies is recommended.

Nocturnal hypoxaemia is common in adults with sickle cell anaemia.

The symptoms and sequelae of sickle cell anaemia (SCA) are caused by the polymerization of deoxygenated sickle haemoglobin, and people with SCA may be uniquely susceptible to adverse outcomes from hypoxia and haemoglobin desaturation. We examined by oximetry adults (aged 18-45 years) with SCA presenting symptoms indicative of polysomnography, at a single institution, irrespective of treatment, for nocturnal hypoxaemia. Clinical labs and blood for in vitro assessments were taken upon enrolment and after 8-12 weeks of oxygen therapy or observation. Of 21 screened participants, nine (43%) had sufficient nocturnal hypoxaemia to warrant oxygen therapy (≥5 min at SpO2 ≤ 88%). Time spent at SpO2 ≤ 88% associated with age (p = 0.0092), annual hospitalizations (p = 0.0018) and anaemia (p = 0.0139), as well as plasma levels of TNFα (p = 0.0019) and IL-4 (p = 0.0147). Longitudinal analysis showed that WBC significantly decreased during the follow-up period in hypoxic individuals but not in non-hypoxic individuals (p = 0.0361 and p = 0.6969 respectively). Plasma levels of CCL2 and IL-1ra tended to increase, while levels of red blood cell reactive oxygen species tended to decrease with oxygen therapy. Overall, nocturnal hypoxaemia was common in this pilot study population and associated with plausible clinical comorbidities; oxygen therapy may decrease inflammation and oxidative damage in hypoxic individuals.

Hydroxyurea for secondary stroke prevention in children with sickle cell anaemia: a systematic review of clinical evidence and outcomes.

Background: Stroke remains one of the leading complications of sickle cell anaemia (SCA) in children. Traditionally, SCA treatment focused on symptom relief. However, the high incidence of strokes in children has prompted a reevaluation of treatment, particularly hydroxyurea, for secondary stroke prevention. This study assesses hydroxyurea's effectiveness and safety in preventing secondary strokes in paediatric SCA patients. Methods: This systematic review followed a pre-defined protocol registered with PROSPERO. Comprehensive searches were conducted across PubMed, Embase, Scopus, MEDLINE, Google Scholar, and the Cochrane Library up to August 2023. Studies were included involving paediatric SCA patients at risk of secondary stroke, assessing hydroxyurea as the primary intervention. Results: A total of six studies meeting inclusion criteria were included. The effectiveness of hydroxyurea in preventing secondary strokes, with variable responses reported across studies. Adverse effects, including mild neutropenia, are associated with hydroxyurea treatment but with variability in reported toxicity levels. Conclusion: Hydroxyurea holds promise in preventing recurrent strokes in children with SCA, though its efficacy and safety profiles vary among individuals. Optimal dosages and treatment durations require further investigation, necessitating vigilant monitoring of haematological parameters. Future research should refine dosing strategies, consider individual patient characteristics, assess long-term effects, and explore ancillary benefits beyond stroke prevention.

The role of preoperative transfusion in sickle cell disease, a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to provide guidance on preoperative blood transfusion strategies for patients with sickle cell disease (SCD). We included all randomized controlled and observational studies exploring the clinical outcomes of preoperative blood transfusion among patients with SCD compared to the conservative transfusion strategy until 14/09/2022. Sixteen studies involving 3486 participants were analysed. The findings revealed a significantly higher bleeding rate in patients who received preoperative transfusion than those who followed a conservative strategy (RR = 4.32, 95% CI 1.75-10.68, P = 0.002, I2 = 0%). However, the two strategies had no significant differences in other clinical outcomes, such as acute chest syndrome, painful crisis, fever, neurological complications, thrombosis, ICU admission, and mortality. It is important to note that all the included studies had a moderate risk of bias. Preoperative transfusion in SCD was associated with a higher bleeding risk but a similar risk in other outcomes compared to conservative strategies. Notably, the increased bleeding risk observed seldom had clinical significance. We recommend individualizing management strategies, considering the overall positive impact of transfusions in reducing complications. Further high-quality studies are needed to refine recommendations.

Acute kidney injury is more common in hospitalised children with sickle cell anaemia in Africa.

AIM: To document the prevalence, severity, hospital outcome and factors associated with acute kidney injury (AKI) in hospitalised children with sickle cell anaemia (SCA). METHODS: In this prospective observational study involving children aged 0.5-17 years with SCA requiring hospitalisation, we used serum creatinine level at 0 and 48 h of hospitalisation to determine the presence of AKI. RESULTS: The study involved 155 children with SCA aged 0.5-17 years with a median (interquartile range) age of 7.8 (4.3-11.0) years. Acute kidney injury occurred in 27 (17.4%) children with 33.3% reaching stage 3. Hepatomegaly (81.5% vs. 55.4%; p = 0.015), splenomegaly (33.3% vs. 10.9%; p = 0.003), dipstick proteinuria (22.2% vs. 5.4%; p = 0.004), and hematuria (29.6% vs. 3.1%; p = <0.001) were more common in those with AKI. In contrast, children with AKI had lower haematocrit (16.9% vs. 22.2%; p = <0.001) and serum bicarbonate (16.7 vs. 19.1 mmoL/L; p = 0.010) compared with those without AKI. Those with AKI had longer hospital stay (median [interquartile range]: 7 [4-12] days vs. 4 [3-6] days; p = 0.008). CONCLUSION: AKI is common among hospitalised children with AKI and is associated with longer hospital stay.

The Danish national haemoglobinopathy screening programme: Report from 16 years of screening in a low-prevalence, non-endemic region.

The Danish national haemoglobinopathy screening programme seeks to determine parental haemoglobinopathy carrier state antenatally. In this retrospective register-based study, we evaluated the 16-year trajectory of this programme, utilising the Danish Red Blood Cell Centre's laboratory database, covering approximately 77% of the Danish population. During the study period, we observed a substantial increase in annual diagnostic examinations performed, from 389 in 2007 to 3030 in 2022. Women constituted 88% of these cases, aligning with the emphasis of the screening programme. Of these, 54% of women of reproductive age (15-40 years) and 10% of women >40 years were specified as pregnant. During our study period, 61 children were born with a severe haemoglobinopathy, out of which 23 children were born from mothers not residing in Denmark during their first trimester thus not included in the screening programme. Prenatal invasive testing was performed for 60 fetuses, identifying 12 with homozygous or compound heterozygous haemoglobinopathy. The Danish haemoglobinopathy screening programme has provided screening, information and reproductive choices for numerous families. During the study period, screening for haemoglobinopathies has been steadily increasing and is expected to continue to increase. Awareness of and adherence to the screening programme is subject of further investigation and optimisation.

Disease severity and renal function among sickle cell anaemia patients in a tertiary hospital, South-south, Nigeria: a cross sectional study.

Background: Renal disease is a recognized complication of sickle cell anaemia (SCA), especially from the third decade of life and is linked to disease severity. This study assessed the association between disease severity and renal function among SCA patients using routine and newer markers of renal function. Methods: This cross-sectional study recruited 85 SCA patients. Disease severity was assessed using modified Adegoke criteria which include the frequency of transfusion, painful crises, packed cell volume, and history of complications such as hypertension and chronic leg ulcers. Renal function was assessed using urea, creatinine, and beta-2-microglobulin (ß2-M). Association was determined between renal function and disease severity using Pearson's correlation. P-value < 0.05 was taken as significant. Results: The mean age of participants was 27.2 ± 7.6 years with 41(48.2%) males and 44 (51.8%) females. The mean packed cell volume, serum creatinine, serum urea, and ß2-M were 24.0± 4.1%,17.6±7.5 mg/dL, 0.7±0.3mg/dL, 3.4±1.2mg/l respectively. A majority (54.1%) of them had a mild disease while 35.3% and 10.6% had moderate and severe diseases, respectively. Forty of the SCA patients had urine specific gravity below 1.010. The mean values of systolic blood pressure (p=0.001) diastolic blood pressure (p=0.001), serum creatinine (p=0.028) and ß2M (p=0.019) significantly increased with disease severity. There was a significant positive correlation between SCA disease severity and serum urea (r=0.229; p=0.035), and serum ß2-microglobulin (r=0.270; p=0.012). Conclusion: Sickle cell anaemia severity is associated with a decline in renal function using both traditional and novel renal markers. Serum ß2-M may serve as a useful marker of renal function and disease severity in SCA.

Cystatin C-derived estimated glomerular filtration rate in children with sickle cell anaemia.

BACKGROUND: Sickle cell disease is the most common inherited blood disorder in humans and constitutes a major public health burden. It is a multisystemic condition with long-term renal complications. Early detection of sickle cell nephropathy and initiation of appropriate interventions are associated with improved survival and quality of life. This study aimed to compare the cystatin C-derived estimated glomerular filtration rate (GFR) of the study groups and also, to correlate the clinical features of chronic kidney disease (CKD) with decreased GFR in children with sickle cell anaemia (SCA). METHODS: This hospital-based cross-sectional analytic study recruited 86 SCA subjects in steady-state and 86 age and sex-matched healthy HbAA controls aged 1-14 years who attended the Paediatric Haematology and Outpatient clinics of Federal Medical Centre Bida over six months. Data were collected using a semi-structured questionnaire, and participants' length/height, weight, and blood pressure were measured using standard procedures. Blood samples were drawn for serum cystatin C assay via the sandwich enzyme-linked immunosorbent assay (ELISA) technique. Filler's equation was used to calculate the glomerular filtration rate. RESULTS: There was a significant difference in the mean cystatin C-derived GFR between the two groups, i.e. 116 ± 30mL/min/1.73m2 vs. 106 ± 24mL/min/1.73m2 for the SCA and control groups, respectively (p = 0.017). The prevalence of supernormal GFR (i.e. GFR > 140mL/min/1.73m2) and decreased GFR (i.e. GFR < 90mL/min/1.73m2) was 19.8% and 22.1%, respectively, in children with SCA. There was no significant association between the age at diagnosis of SCA, blood transfusions, blood pressure, packed cell volume and presence of peripheral oedema with decreased GFR in the study subjects. CONCLUSIONS: Supernormal GFR is common in children with SCA and there is no significant association between clinical features of CKD with decreased GFR. Regular evaluation of renal function is, however, recommended in children with SCA for early detection and treatment of renal complications in order to halt the progression to end-stage kidney disease (ESKD).

The role of tocilizumab in the treatment of post-transfusion hyperhaemolysis.

Hyperhaemolysis syndrome (HHS) is a serious complication of transfusion mostly reported in patients with sickle cell disease. HHS is characterised by the destruction of both donor and autologous red blood cells. Tocilizumab is a recombinant humanised monoclonal antibody that inhibits the binding of interleukin-6 and has been used in the treatment of severe/critical coronavirus disease 2019 infection but also some cases of HHS. We describe two further cases of HHS successfully treated with tocilizumab and propose a decision aid for when to consider this treatment.

A Review of the Relationship between the Immune Response, Inflammation, Oxidative Stress, and the Pathogenesis of Sickle Cell Anaemia.

Sickle cell anaemia (SCD) is a life-threatening haematological disorder which is predominant in sub-Saharan Africa and is triggered by a genetic mutation of the ß-chain haemoglobin gene resulting in the substitution of glutamic acid with valine. This mutation leads to the production of an abnormal haemoglobin molecule called haemoglobin S (HbS). When deoxygenated, haemoglobin S (HbS) polymerises and results in a sickle-shaped red blood cell which is rigid and has a significantly shortened life span. Various reports have shown a strong link between oxidative stress, inflammation, the immune response, and the pathogenesis of sickle cell disease. The consequence of these processes leads to the development of vasculopathy (disease of the blood vessels) and several other complications. The role of the immune system, particularly the innate immune system, in the pathogenesis of SCD has become increasingly clear in recent years of research; however, little is known about the roles of the adaptive immune system in this disease. This review examines the interaction between the immune system, inflammation, oxidative stress, blood transfusion, and their effects on the pathogenesis of sickle cell anaemia.

Provider prescription of hydroxyurea in youth and adults with sickle cell disease: A review of prescription barriers and facilitators.

Sickle cell disease (SCD) is an inherited red blood cell disorder associated with frequent painful events and organ damage. Hydroxyurea (HU) is the recommended evidence-based treatment of SCD. However, among patients eligible for HU, prescription rates are low. Utilizing a scoping review approach, we summarized and synthesized relevant findings regarding provider barriers and facilitators to the prescription of HU in youth and adults with SCD and provided suggestions for future implementation strategies to improve prescription rates. Relevant databases were searched using specified search terms. Articles reporting provider barriers and/or facilitators to prescribing HU were included. A total of 10 studies met the inclusion criteria. Common barriers to the prescription of HU identified by providers included: doubts around patients' adherence to HU and their engaging in required testing, concerns about side effects, lack of knowledge, cost and patient concerns about side effects. Facilitators to the prescription of HU included beliefs in the effectiveness of HU, provider demographics and knowledge. Findings suggest significant provider biases exist, particularly in the form of negative perceptions towards patients' ability to adhere to taking HU and engaging in the required follow-up. Improving provider knowledge and attitudes towards HU and SCD may help improve low prescription rates.