UNASSIGNED: Sickle cell disease is an inherited disorder characterized by hemoglobin S polymerization leading to vaso-occlusion and hemolytic anemia. These result in a variety of pathological events, causing both acute and chronic complications. Millions around the world are affected by sickle cell disease with predominance in sub-Saharan Africa. Hydroxyurea was the first drug approved for use in sickle cell disease to reduce occurrence of painful crises and blood transfusions in patients with frequent, moderate to severe painful crises.
UNASSIGNED: With the development of new therapeutics, the role of hydroxyurea is evolving. This narrative review aims to provide clinical data, safety information, and supplementary evidence for the role of hydroxyurea in the current era of sickle cell disease. A comprehensive literature search of databases, including PubMed and Cochrane Library, was conducted from 1963-2024.
UNASSIGNED: Even though new medications have been approved for sickle cell disease, hydroxyurea remains the gold standard. Hydroxyurea is not only a disease modifier, but it has additional clinical benefits, it is affordable, and its longevity has prompted expanded research in areas such as underutilization and pharmacogenomics. As the treatment landscape evolves, hydroxyurea\'s long-standing record of efficacy and safety continues to support its role as a key agent in disease management.

Intravenous mercury poisoning is a rare but severe medical emergency, often resulting from accidental exposure or intentional self-harm. We present the case of a 30-year-old male with a history of sickle cell anemia who presented with high-grade fever, vomiting, giddiness, and breathlessness following intravenous mercury self-administration. Diagnostic challenges included distinguishing symptoms of acute mercury toxicity from those of his chronic condition of sickle cell trait. Markedly elevated serum mercury levels confirmed the diagnosis, with high-resolution computed tomography (HRCT) imaging studies revealing mercury deposits and alveolar lung injury. Management involved antidote of mercury poisoning, including non-invasive ventilation and transfusions, with consultations from multiple specialties. The patient demonstrated significant clinical improvement and was discharged with scheduled follow-ups. This case underscores the complexity of diagnosing and managing intravenous mercury poisoning, highlighting the importance of a comprehensive multidisciplinary approach for optimal patient outcomes.

Sickle Cell Anemia (SCA) is a hereditary blood disorder characterized by the presence of abnormal hemoglobin, leading to the formation of sickle-shaped red blood cells. While extensive research has unraveled many aspects of the genetic and molecular basis of SCA, the role of telomere dynamics in disease progression remains a relatively unexplored frontier. This review seeks to provide a comprehensive examination of telomere biology within the context of SCA, aiming to elucidate its potential impact on molecular aging and the progression of the disease. The impact of oxidative stress on telomere dynamics in SCA is explored, with a particular focus on how increased reactive oxygen species (ROS) may contribute to accelerated telomere shortening and genomic instability. Furthermore, the potential relationship between telomere dysfunction and cellular senescence in SCA is investigated, shedding light on how telomere dynamics may contribute to the premature aging of cells in this population. The review concludes by summarizing key findings and proposing potential therapeutic strategies targeting telomere dynamics to mitigate disease progression in SCA. It also identifies gaps in current understanding and suggests avenues for future research, emphasizing the importance of further investigating telomere biology to advance our understanding of molecular aging and disease progression in Sickle Cell Anemia. This comprehensive exploration of telomere dynamics in SCA offers insights into potential mechanisms of molecular aging and disease progression, paving the way for targeted therapeutic interventions and improved disease management.

Sickle cell anemia (SCA) is a multisystem disease, associated with increased risk for infection and thromboembolic disease, and pregnancy is a stressor for patients with SCA. In general, coronavirus disease 2019 (COVID-19) infection in SCA is associated with a favorable outcome. Literature of pregnancy in SCA with COVID is scarce. We report a case series study of pregnant women with SCA, who are confirmed positive for COVID-19 from May 2020 to March 2021. These patients showed generally mild-to-moderate disease and presented predominantly with fever and painful crisis. They showed a significant drop in Hb from baseline, and they received low-molecular-weight heparin prophylaxis (LMWH) and blood transfusion. The outcome of pregnancy is satisfactory, although the mean birth weight was significantly lower than that reported from the same SCA population.

Red blood cells (RBCs) become sickle-shaped and stiff under hypoxia as a consequence of hemoglobin (Hb) polymerization in sickle cell anemia. Distinguishing between sickle cell disease and trait is crucial during the diagnosis of sickle cell disease. While genetic analysis or high-performance liquid chromatography (HPLC) can accurately differentiate between these two genotypes, these tests are unsuitable for field use. Here, we report a novel microscopy-based diagnostic test called ShapeDx™ to distinguish between disease and trait blood in less than 1 h. This is achieved by mixing an unknown blood sample with low and high concentrations of a chemical oxygen scavenger and thereby subjecting the blood to slow and fast hypoxia, respectively. The different rates of Hb polymerization resulting from slow and fast hypoxia lead to two distinct RBC shape distributions in the same blood sample, which allows us to identify it as healthy, trait, or disease. The controlled hypoxic environment necessary for differential Hb polymerization is generated using an imaging microchamber, which also reduces the sickling time of trait blood from several hours to just 30 min. In a single-blinded proof-of-concept study conducted on a small cohort of clinical samples, the results of the ShapeDx™ test were 100% concordant with HPLC results. Additionally, our field studies have demonstrated that ShapeDx™ is the first reported microscopy test capable of distinguishing between sickle cell disease and trait samples in resource-limited settings with the same accuracy as a gold standard test.

BACKGROUND: The data to support chronic automated red cell exchange (RCE) in sickle cell disease (SCD) outside of stroke prevention, is limited, especially in adults.
METHODS: A retrospective analysis was conducted of patients with SCD who were referred for chronic RCE at our institution over a 10-year period. Data that were evaluated included patient demographics, referral indications, and procedural details (e.g., vascular access, adverse events, etc.). In a subanalysis, the number of annual acute care encounters during 3 years of chronic RCE was compared with that in the year preceding the first RCE.
RESULTS: A total of 164 patients were referred for chronic RCE: median age was 28 years (interquartile range [IQR] = 22-36) at referral and 60% were female. Seventy (42.6%) were naïve to chronic transfusion (simple or RCE) prior to referral. The leading indications for referral were refractory pain (73/164, 44.5%) and iron overload (57/164, 34.7%). A total of 5090 procedures occurred during the study period (median = 19, IQR = 5-45). Of the 138 patients who had central vascular access, 8 (6%) and 16 (12%) had ≥1 central-line-related thrombosis and/or infection, respectively. Of those who were not RBC alloimmunized at initiation of RCE, 12/105 (11.4%) developed new antibodies during chronic RCE. In those 30 patients who were adherent to therapy for 3 years, there was no significant difference in acute care encounters following initiation of RCE.
CONCLUSIONS: Prospective clinical trials are needed to determine which patients are most likely to benefit from chronic RCE and refine selection accordingly.

A growing body of research is categorizing sex differences in both sickle cell anemia (SCA) and acute kidney injury (AKI); however, most of this work is being conducted in high-resource settings. Here, we evaluated risk factors and clinical parameters associated with AKI and AKI severity, stratified by sex, in a cohort of children hospitalized with SCA and vaso-occlusive pain crisis (VOC). The purpose of this study was to explore sex disparities in a high-risk, vulnerable population. This study was a secondary analysis of data collected from a cohort of Ugandan children between 2 and 18 yr of age prospectively enrolled. A total of 185 children were enrolled in the primary study; 41.6% were female and 58.4% were male, with a median age of 8.9 yr. Incident or worsening AKI (P = 0.026) occurred more frequently in female compared with male children, despite no differences in AKI on admission. Female children also had altered markers of renal function including higher creatinine levels at admission (P = 0.03), higher peak creatinine (P = 0.006), and higher urine neutrophil gelatinase-associated lipocalin (NGAL) at admission (P = 0.003) compared with male children. Female children had elevated total (P = 0.045) and conjugated bilirubin at admission (P = 0.02) compared with male children and higher rates of hematuria at admission (P = 0.004). Here, we report sex differences in AKI in children with SCA and VOC, including increased incidence and worsening of AKI in female pediatric patients, in association with an increase in biological indicators of poor renal function including creatinine, estimated glomerular filtration rate, and NGAL.NEW & NOTEWORTHY In this study, we report an increased risk of developing acute kidney injury (AKI) during hospitalization, worsening AKI, and death among females with sickle cell anemia (SCA) hospitalized with an acute pain crisis compared with males. The sex differences in AKI were not explained by socioeconomic differences, severity of pain, or disease severity among females compared with males. Together, these data suggest that female children with SCA may be at increased risk of AKI.

Sickle cell anemia (SCA), the most common form of sickle cell disease (SCD), is a genetic blood disorder. Red blood cells break down prematurely, causing anemia and often blocking blood vessels, leading to chronic pain, organ damage, and increased infection risk. SCD arises from a single-nucleotide mutation in the β-globin gene, substituting glutamic acid with valine in the β-globin chain. This review examines treatments evaluated through randomized controlled trials for managing SCD, analyzes the potential of functional foods (dietary components with health benefits) as a complementary strategy, and explores the use of bioactive compounds as functional food ingredients. While randomized trials show promise for certain drugs, functional foods enriched with bioactive compounds also hold therapeutic potential. Further research is needed to confirm clinical efficacy, optimal dosages, and specific effects of these compounds on SCD, potentially offering a cost-effective and accessible approach to managing the disease.

UNASSIGNED: The neurocognitive functions in Ugandan children aged 1-12 years with sickle cell anemia (SCA) were compared to their non-SCA siblings to identify risk factors for disease-associated impairment.
UNASSIGNED: This cross-sectional study of the neurocognitive functions in children with SCA (N = 242) and non-SCA siblings (N = 127) used age- and linguistically appropriate standardized tests of cognition, executive function, and attention for children ages 1-4 and 5-12. Test scores were converted to locally derived age-normalized z-scores. The SCA group underwent a standardized stroke examination for prior stroke and transcranial Doppler ultrasound to determine stroke risk by arterial flow velocity.
UNASSIGNED: The SCA group was younger than their siblings (mean ages 5.46 ± 3.0 vs. 7.11 ± 3.51 years, respectively; p < 0.001), with a lower hemoglobin concentration (7.32 ± 1.02 vs. 12.06 ± 1.42, p < 0.001). The overall cognitive SCA z-scores were lower, -0.73 ± 0.98, vs. siblings, -0.25 ± 1.12 (p < 0.001), with comparable findings for executive function of -1.09 ± 0.94 vs. -0.84 ± 1.26 (p = 0.045), respectively. The attention z-scores for ages 5-12 for the SCA group and control group were similar: -0.37 ± 1.4 vs. -0.11 ± 0.17 (p = 0.09). The overall differences in SCA status were largely driven by the older age group, as the z-scores in the younger subsample did not differ from controls. Analyses revealed the strongest predictors of poor neurocognitive outcomes among the SCA sample to be the disease, age, and prior stroke (each p < 0.001). The impacts of anemia and SCA were indistinguishable.
UNASSIGNED: Neurocognitive testing in children with SCA compared to non-SCA siblings revealed poorer SCA-associated functioning in children older than age 4. The results indicate the need for trials assessing the impact of disease modification on children with SCA.

A universal newborn screening program for sickle cell disease (uNS-SCD) was implemented in the province of Québec (Qc) in November 2013, close in time to the recommendation of early initiation of hydroxyurea (HU) therapy for children. This retrospective cohort study evaluated the impact of such a program on children first seen between January 2000 and December 2019. Cohorts pre-SCD-uNS in Qc (pre-QcNS) (n = 253) and post-QcNS (n = 157) for patients seen prior to or after Nov 2013 were compared. Kaplan-Meier curves, Poisson regression, and logistic regressions were used for statistical analysis, using Software R version 4.2.1. Median age at first visit decreased significantly from 14.4 [interquartile range: 2.4-72.0] to 1.2 months [1.2-57.6] (p < 0.001). The percentage of children born in Qc undiagnosed at birth and referred after a first SCD-related complication dropped from 42.6% to 0.0% (p < 0.0001). The median age of HU introduction for patients with SS/Sβ°-thalassemia decreased from 56.4 [31.2-96.0] to 9.0 months post-QcNS [8.0-12.1] (p < 0.001). Event-free survival improved significantly for any type of hospitalization as well as for vaso-occlusive crisis (VOC) (140-257 days (p < 0.001) and 1320 vs. 573 days (p < 0.002), respectively), resulting in a reduction from 2 [interquartile range: 1.0-3.0] to 1.0 hospitalizations/patient-year [0.6-1.4] (p < 0.001). Children with SS/Sβ°-thalassemia referred post-QcNS also had fewer emergency department visits for VOC (RR: 0.69, 95% confidence interval: 0.54-0.88). The Universal NS program allows early detection and referral of children with SCD to comprehensive care centers. Earlier access ensures that children benefit from essential preventive interventions, reducing disease burden. This cohort study highlights that uNS-SCD is an essential public health measure.