Diagnosis Of Sickle Cell Disease Research Articles

Barriers and facilitators to community acceptability of integrating point-of-care testing to screen for sickle cell disease in children in primary healthcare settings in rural Upper East Region of Northern Ghana.

Sickle cell disease (SCD) remains a public health problem especially in sub-Saharan Africa including Ghana. While pilot initiatives in Africa have demonstrated that neonatal screening coupled with early intervention reduces SCD-related morbidity and mortality, only 50-70% of screen-positive babies have been successfully retrieved to benefit from these interventions. Point-of-care testing (POCT) with high specificity and sensitivity for SCD screening can be integrated into existing immunization programs in Africa to improve retrieval rates. This study explored community acceptability of integrating POCT to screen for SCD in children under 5 years of age in primary healthcare facilities in Northern Ghana. This was an exploratory study using qualitative research approach where 10 focus group discussions and 20 in-depth interviews were conducted with community members and health workers between April and June 2022. The recorded interviews were transcribed verbatim after repeatedly listening to the recordings. Data was coded into themes using QSR Nvivo 12 software before thematic analysis. Most participants (70.9%) described SCD as serious and potentially life-threatening condition affecting children in the area. Of 148 community members and health workers, 141 (95.2%) said the screening exercise could facilitate diagnosis of SCD in children for early management. However, discrimination, fear of being tested positive, stigmatization, negative health worker attitude linked with issues of maintaining confidentiality were reported by participants as key factors that could affect uptake of the SCD screening exercise. Most participants suggested that intensive health education (78.3%), positive attitude of health workers (69.5%), and screening health workers not being biased (58.8%) could promote community acceptability. A large majority of participants viewed screening of SCD in children as very important. However, opinions expressed by most participants suggest that health education and professionalism of health workers in keeping patients' information confidential could improve the uptake of the exercise.

Aptamer-based label-free electrochemical biosensors for the diagnosis of sickle cell anemia

Aptamer-based label-free electrochemical biosensors for the diagnosis of sickle cell anemia

The Association between Sickle Cell Disease and Postpartum Severe Maternal Morbidity.

To compare the risk of severe maternal morbidity (SMM) from the delivery admission to 42 days' postdischarge among persons with sickle cell disease (SCD) to those without SCD. This retrospective cohort study included deliveries ≥20 weeks' gestation at an urban safety net hospital in Atlanta, GA from 2011 to 2019. The exposure was SCD diagnosis. The outcome was a composite of SMM from the delivery admission to 42 days' postdischarge. SMM indicators as defined by the Centers for Disease Control and Prevention were identified using the International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/10) codes; transfusion of blood products and sickle cell crisis were excluded. Of N = 17,354 delivery admissions, n = 92 (0.53%) had SCD. Persons with SCD versus without SCD had an increased risk of composite SMM (15.22 vs. 2.29%, p < 0.001), acute renal failure (6.52 vs. 0.71%, p < 0.001), acute respiratory distress syndrome (4.35 vs. 0.17%, p < 0.001), puerperal cerebrovascular disorders (3.26 vs. 0.10%, p < 0.001), sepsis (4.35 vs. 0.42%, p < 0.01), air and thrombotic embolism (5.43 vs. 0.10%, p < 0.001), and ventilation (2.17 vs. 0.09%, p < 0.01). Ultimately, those with SCD had an approximately 6-fold higher incidence risk ratio of SMM, which remained after adjustment for confounders (adjusted incidence risk ratio [aIRR]: 5.96, 95% confidence interval [CI]: 3.4-9.19, p < 0.001). Persons with SCD in active vaso-occlusive crisis at the delivery admission had an approximately 9-fold higher risk of SMM up to 42 days' postdischarge compared with those with SCD not in crisis at the delivery admission (incidence: 25.71 vs. 8.77%, p < 0.05; aIRR: 8.92, 95% CI: 4.5-10.04, p < 0.05). Among those with SCD, SMM at the delivery admission was primarily related to renal and cerebrovascular events, whereas most postpartum SMM was related to respiratory events or sepsis. SCD is significantly associated with an increased risk of SMM during the delivery admission and through 42 days' postdischarge. Active crisis at delivery further increases the risk of SMM. · Sickle cell disease was associated with an approximately 6-fold increased risk of SMM.. · Active vaso-occlusive crisis at delivery was associated with an approximately 9-fold increased risk of SMM.. · 48% of SMM events in persons with SCD occurred postpartum and were respiratory- or sepsis-related..

Impact of hospitalized vaso-occlusive crises in the previous calendar year on mortality and complications in adults with sickle cell disease: a French population-based study

BackgroundHistorically, sickle cell disease (SCD) patients experiencing frequent hospitalized vaso-occlusive crises (HVOC) have been associated with increased mortality, yet recent data reflecting the widespread use of hydroxyurea and advancements in disease management remain limited. Our study aims to assess the association between HVOC and mortality or severe complications in patients with SCD in this new treatment landscape. MethodsThis was a retrospective observational cohort study using the French national health data system. Between 01-01-2012 and 12-31-2018, all SCD patients ≥16 years old (ICD-10 codes D57·0-2) were included and followed until 12-31-2018. HVOC was defined as a hospitalization of ≥1 night with primary diagnosis of SCD with crisis, following an emergency room visit. The association between HVOC and severe complications was assessed with a Cox proportional hazards model. FindingsIn total, 8 018 patients (56·6% females; 4 538/8 018) were included. The 2018 SCD standardized one-year period prevalence was 17·9 cases/100 000 person-years [17·4;18·3]. The mean rate was 0.84 (1·88) HVOC/person-year. In 2018, 70% (5 323/7 605), 22% (1 671/7 605), and 8% (611/7 605) of patients experienced 0, 1–2, or 3+ HVOCs, respectively. The median survival time between HVOCs was 415 days [386;439]. Overall, 312 patients died (3·9%) with a mean age of 49·8 (19·4). Compared to patients without HVOC, the hazard ratios of death in patients with 1–2 or 3+ HVOCs the year prior to death were 1·67 [1·21;2·30] and 3·70 [2·30;5·93], respectively. Incidence of acute chest syndrome, pulmonary embolism, osteonecrosis, and sepsis increased with the HVOCs category, but not stroke. In 2018, 29·5% (180 / 611) of patients with 3+ HVOCs did not take hydroxyurea. InterpretationPatients must be closely monitored during their hospitalizations to intensify treatment and check treatment compliance. Innovative therapies are also required. FundingThe study was funded by Novartis.

Abstract 3470: Evaluation of the association between sickle cell disease and breast cancer using the All of Us Research Program dataset

Abstract Background: The All of Us Research Program (AoURP) dataset was used to evaluate pharmacological treatment modalities in patients with both breast cancer (BC) and sickle cell disease (SCD). This study aims to identify treatment strategies for sickle cell patients with BC that may inform improved treatment options for patients living with either or both conditions, as there is an imminent need in this patient population. Methods: We investigated the relationship between SCD and BC using the AoURP dataset. Criteria were female patients with a confirmed diagnosis of concomitant SCD and BC were selected. Hematologic, antineoplastics, and immunomodulating agents prescribed to patients were identified. Analysis was conducted in a Jupyter Notebook environment by way of R. Using FDA-approved and off-label indications, medication use patterns were used to reverse-engineer patient information and identify trends between SCD and BC. Results: Nine female patients had concomitant diagnoses of SCD and BC, which aligned with the inclusion criteria. African Americans were significantly represented in this cohort, making up sixty-seven of patients. Twenty-two percent of patients did not indicate race, while eleven percent of patients identified as Caucasian. All patients included in the study were prescribed anemic therapy. Eleven percent of patients were prescribed an FDA-approved medication for SCD. Seventy-eight percent of patients were prescribed hormone-targeted BC medications. Thirty-three percent of patients were prescribed the immunotherapy regimen, Dinutuximab with adjunctive interferon-alpha. Eleven percent of patients were prescribed cytotoxic therapy. Conclusion: Further investigation is warranted for dinutuximab use in BC treatment, specifically the triple negative subtype, as currently no targeted therapeutic options exist, and prognosis is poor. The data suggests dinutuximab with adjunctive interferon-alpha may be promising for triple-negative BC patients with SCD. Citation Format: Ivan T. Jubilee, Lauren K. Evans, KiTani Parker Lemieux. Evaluation of the association between sickle cell disease and breast cancer using the All of Us Research Program dataset [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3470.

Iowa Newborn Screening Program Experience with Hemoglobinopathy Screening over the Last Two Decades and Its Increasing Global Relevance.

Hemoglobinopathies are the commonest monogenic disorder worldwide, with approximately seven percent of the world population being carriers of hemoglobinopathies. The healthcare utilization impact of thalassemia has resulted in global public health initiatives to screen for hemoglobinopathies, especially sickle cell disease (SCD). The Iowa Newborn Screening Program (INSP) has been in place for more than 50 years with a primary focus on detecting SCD. Recent changes in migration patterns have led to a global distribution of hemoglobinopathies in the western world, which has translated to an increase in the diagnosis of SCD and the incidental detection of non-sickling hemoglobinopathies within the INSP. This study documents the birth prevalence of hemoglobinopathies diagnosed in newborns through the INSP and highlights the need for newborn screening programs to evolve to meet the healthcare needs of underserved, minority populations.

Dental caries in the permanent dentition and health-related quality of life among children and adolescents with sickle cell disease.

The aim was to associate living, health and oral health conditions with the quality of life (QL) of children and adolescents (CA) with sickle cell disease (SCD). Of the 120 eligible users of a public hematological service, 106 CA with SCD from 6 to 18 years of age, and their caregivers, answered semi-structured questions about socio-demographic, health and oral health conditions. For QL, we used the validated instrument PedsQLSCD™. The oral clinical examination occurred according to the guidelines of WHO and SB Brazil 2010. The majority of CA were non-white people (88%), mean age of 10.4 (±2.9) years, family income of up to two monthly minimum wages, for 03 to 05 members, with diagnosis of sickle cell anemia by neonatal screening, hospitalizations were due allergic crises, polypharmacy and dental caries (51%) were present. "About the Impact of My Pain" was the best-fit model for the QLSCD (adjusted R²=56%; AIC=28.67; p=0.04). Dental caries in permanent dentition worsened the QLSCD (OR=0.53; IC95%=0.35-0.78; p<0.05) and was associated with the type of school, car ownership, number of family members, of complications and of the medications. To overcome this scenario, programmatic actions are required, and implementation of public policies specifically directed towards these groups.

Impact of Race, Socioeconomic Status, and Geography on Healthcare Outcomes for Children With Sickle Cell Disease in the United States: A Scoping Review.

A large proportionof patients with sickle cell disease (SCD) identify as Black or African American (AA). Social bias and stigma in healthcare outcomes for children with SCD are impossible to explore without considering the impact of racial/cultural identity, socioeconomic status (SES), and geography. It is important to understand the current influences of social movements, expanded health insurance coverage, and telehealth on these variables when considering healthcare outcomes for patients with SCD. The objective of this study was to determine the roles of racial identity, SES, and geography in healthcare outcomes for the pediatric population of children with SCD in the United States (US). This study is a scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases utilized included Cochrane, CINHAL, Medline, and Nursing and Allied Health Collection, all accessed through the EBSCO Information Services. Studies met the following inclusion criteria: published in English, pediatric patients residing in the US, and published between 2017 and 2022. Search terms included "sickle cell" AND "pediatric", which were then combined with "minority" OR "racial" OR "rural" OR "urban" OR "poverty" OR "income" OR "socioeconomic status". The initial search yielded 635 unique articles, with 17 articles meeting full inclusion criteria. Overall, it was clear that there are examples of positive effects of race, low SES, and rural geographic location on positive health outcomes, though a large number of studies oscillated between showing negative associations or no association at all. Barriers to care for patients with SCD are multifaceted, making it difficult to isolate and analyze the impact of individual variables. Many studies demonstrated the significance of family, community, and institutional relationships as positive support for patients with SCD. This review highlights the need for additional research on the healthcare outcome benefits of patient/familial support groups aiming to bring together patients who share racial experience and SCD diagnosis regardless of SES and geography.

Knowledge and practices of sickle cell disease among healthcare providers in Kinshasa, Democratic Republic of the Congo.

In Kinshasa, Democratic Republic of Congo, there is a low evocation of the diagnosis of sickle cell disease (SCD) by first-level healthcare providers (HCPs), most likely because of poor knowledge of the disease. To assess the levels of knowledge and practices of SCD and to identify determinants of the practices among primary HCPs. Healthcare facilities in Selembao health zone in Kinshasa, Democratic Republic of the Congo. A cross-sectional study of HCPs randomly selected through a two-stage sampling design. Data were collected using a pre-tested interviewer-administered questionnaire. Univariate and bivariate analysis were done to describe the levels of knowledge and practices of SCD. Factors associated with better practices on SCD were determined using multiple linear regression. The threshold for statistical significance wasp˂ 0.05. A total of 318 HCPs, which included 80 physicians and 238 nurses, participated in the study. The participants showed different scores on the components of the knowledge. All the participants showed poor practices on SCD. Multiple linear regression retained overall knowledge of SCD as a significant predictor of better practice for physicians. Knowledge of SCD and duration of work experience were significant predictors of better practices among nurses. The practices of healthcare providers on SCD were far from optimal. These practices were significantly associated with knowledge and experience of healthcare providers.Contribution:This study highlighted the need for continuing professional education to enhance the management of SCD in the setting.

Crowdsourced human-based computational approach for tagging peripheral blood smear sample images from Sickle Cell Disease patients using non-expert users

In this paper, we present a human-based computation approach for the analysis of peripheral blood smear (PBS) images images in patients with Sickle Cell Disease (SCD). We used the Mechanical Turk microtask market to crowdsource the labeling of PBS images. We then use the expert-tagged erythrocytesIDB dataset to assess the accuracy and reliability of our proposal. Our results showed that when a robust consensus is achieved among the Mechanical Turk workers, probability of error is very low, based on comparison with expert analysis. This suggests that our proposed approach can be used to annotate datasets of PBS images, which can then be used to train automated methods for the diagnosis of SCD. In future work, we plan to explore the potential integration of our findings with outcomes obtained through automated methodologies. This could lead to the development of more accurate and reliable methods for the diagnosis of SCD.

Therapy with bone marrow mesenchymal stem cells in bone regeneration in children with osteonecrosis secondary to sickle cell disease.

This study aimed to describe the evolution of bone regeneration in children with hip osteonecrosis associated with sickle cell disease, treated with bone marrow-derived mesenchymal stem cell implants at the Professor Edgar Santos University Hospital Complex. A non-randomized clinical trial was conducted with 48 patients of both sexes, aged between 11 and 18years, diagnosed with femoral head osteonecrosis secondary to sickle cell disease. Patient selection was based on strict criteria, including confirmed diagnosis of sickle cell anemia and a stage of osteonecrosis compatible with the proposed treatment. Bone regeneration assessment was performed through radiographic examinations and magnetic resonance imaging, following the Ficat & Arlet criteria and the Salter-Thompson classification. Statistical analysis revealed a significant association between the patients' age and positive treatment outcomes, suggesting that autologous bone marrow cell implantation is a safe and effective approach in the early stages of osteonecrosis. The majority of patients (87.5%) reported complete pain relief, while 10.42% experienced significant symptom improvement. Only one patient (2.08%) did not observe improvement. The results indicate that cell therapy can regenerate or slow the progression of bone necrosis, reducing the need for more invasive surgical procedures. The study demonstrates the potential of bone marrow-derived mesenchymal stem cell implantation in treating hip osteonecrosis in children with sickle cell disease, emphasizing the importance of long-term monitoring of bone structure stability.

Acute unilateral childhood proptosis as a presenting symptom of sickle cell disease

Although rare, orbital bone marrow infarction is a serious complication in patients with sickle cell disease (SCD). Ophthalmologists should have a high index of suspicion for this disease in cases of acute childhood proptosis. Appropriate early management will prevent optic nerve dysfunction and permanent vision loss. Here, we present a case where the patient presented to the ophthalmologist with complaints of pain and proptosis, which led to the diagnosis of SCD.

Implementación de la PCR digital para el diagnóstico prenatal no invasivo de la enfermedad de células falciformes. Estudio piloto

Sickle Cell Disease (SCD) is one of the most prevalent autosomal recessive disease, affecting over 600,000 newborns globally each year. In Spain, the Spanish Registry of Hemoglobinopathies (REHem) has registered 1142 cases. Despite improvements in treatments, prophylaxis, and vaccines, it remains a chronic condition requiring lifelong care. Allogeneic transplantation is the only cure, contingent upon the availability of an HLA-compatible donor. SCD is considered a rare disease in some population, resulting from a mutation of a single nucleotide in codon 6 GAG&gt;GTG (HBB: c.20A&gt;T) of the β-globin gene, producing hemoglobin S (HbS), altering the shape of red blood cells and obstructing circulation, leading to severe complications in multiple organs. Heterozygous individuals (βS/βA) have the ‘sickle cell trait,’ typically asymptomatic. Homozygotes experience symptomatic disease, with chronic and acute infarctions in organs and tissues, episodes of intense pain, cerebral infarctions, splenomegaly, massive hemolytic episodes, and acute chest syndrome, causing a risk of premature death increasing the threat of premature mortality. Prenatal diagnosis provides expecting couples with information about the fetus’s genetic health, enabling informed decision-making. Although conventional techniques are invasive and carry risks, Non-Invasive Prenatal Diagnosis (NIPD) has been developed using cell free fetal DNA (cffDNA) in maternal blood to determine the fetus’s genotype. However, the co-presence of maternal DNA and cffDNA, along with the low concentration of the latter, has been a challenge in non-invasive studies. We present the results of a pilot study where the use of digital PCR (dPCR) has been established for NIPD of SCD, a highly sensitive technique allowing the detection of mutations in low-frequency samples, presenting itself as a safe alternative for SCD diagnosis.

Performance evaluation of the Hemotype SCTM rapid test for the diagnosis of sickle cell disease

Introduction: The use of Rapid Orientation Diagnostic Tests ("RODTs") could play an important role in the mass screening of certain diseases. It saves a great deal of time while managing the flow of samples and the difficulties associated with their storage. This study aimed to identify the impact of the delay between sampling and analysis on the analytical performance of the Hemotype RODT SCTM. Methods: This was a descriptive cross-sectional study conducted over one month. The Immunology-Hematology Department of the CHU de Cocody served as the study setting. The study population consisted of sickle cell patients and hemoglobin C carriers of all ages and sexes. We performed hemoglobin electrophoresis on all samples on the day of collection (D0) and the Hemotype SCTM rapid test on D0, D2, D4, and D6. Sensitivity and specificity were used to determine analytical performance, and the chi2 test was used to compare qualitative variables. Results: The study involved 102 patients with a median age of 16 years (IQR: 9-24). Half of the participants (56.96%) were SSFA2 homozygous sickle cell disease major. On average, 87.1% of RODT results were valid from D0 to D6. At D0, the RODT had a sensitivity of 75% and a specificity of 81.40% for Hb A; Hb S had a sensitivity of 79.80% and a specificity of 100%; Hb C had a sensitivity of 35.71% and a specificity of 98.65%. The sensitivity of Hb C and the specificity of Hb A had increased statistically significantly over time. Cross-referencing the RODT results from D0 to D6 with those of electrophoresis showed a concordance of 86.95% for the AA phenotype, 79.52% for AS; 88.52% for SS; and 95.45% for SC. Conclusion: The HemoTypeSC™ test, with a sensitivity of 75% and specificity of 98% is suitable in certain areas where access to electrophoresis is limited. This performance is not impaired on samples stored for 6 days

Differential sensitivity to hypoxia enables shape‐based classification of sickle cell disease and trait blood samples at point of care

AbstractRed 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.

Real-world observational study on the long-term effect of L-glutamine treatment on renal parameters of adult and pediatric patients with sickle cell disease.

Sickle cell disease (SCD) is a rare genetic blood condition affecting millions worldwide. Oxidative stress is a key player in the pathogenesis of SCD and its comorbid consequences. Renal function impairment is a common complication of SCD in both pediatric and adult patients with serious consequences leading to increased risk of mortality. In this observational real-world study, we are reporting the long-term (120 weeks) renal function in 10 patients treated with L-glutamine. Ten patients (4 pediatric and 6 adults), with confirmed diagnoses of SCD (HbSS genotype), were enrolled, these included four patients from Qatar with Arab Indian haplotype and six patients from French Guiana with African haplotype. All patients were treated with L-glutamine oral powder (~0.3 g/kg body weight, Endari®) twice daily for 120 weeks. Clinical events and laboratory parameters (renal function, hemoglobin, reticulocytes, and lactate dehydrogenase [LDH]) were measured at baseline, 48, and 120 weeks. The study showed that with L-glutamine treatment there were improvements in renal and hematological parameters with no vaso-occlusive crisis at both 48-and 120-week follow-up time points in all 10 patients. Improvements were seen in the albumin creatinine ratio (ACR) from baseline to 48 weeks (mean [Standard deviation SD] ACR: -4.19 [9.81] mg/g) and 120 weeks (mean [SD] ACR: -12.31 [21.09] mg/g). Mean (SD) increase in hemoglobin concentrations from baseline to 48 weeks and 120 weeks was 0.72 (1) g/dL and 1.41 (0.79) g/dL, respectively. Mean (SD) reticulocyte counts and LDH levels decreased from baseline to 48 weeks (mean [SD] change from baseline to 48 weeks, reticulocyte counts: -40.30 [101.58] × 109 cells/L; LDH levels: -259 [154.93] U/L) and 120 weeks (mean [SD] change from baseline to 120 weeks, reticulocyte counts: -58.30 [128.38] × 109 cells/L; LDH levels: -344.80 [274.63] U/L). This is one of the first studies that assessed the long-term renal outcomes in SCD using L-glutamine. L-glutamine improved the renal function in patients with SCD along with improvements in clinical outcomes and hemolysis, from 48 weeks and sustained through 120 weeks of treatment.

Il gioco delle parti: bronchiolite e drepanocitosi

The case of a 2-month-old Senegalese infant with severe anaemia and RSV-related bronchiolitis is described. The Authors stress the role of common infections in leading to the diagnosis of sickle cell anaemia.

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

BackgroundSickle 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).MethodsThis 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.ResultsThere 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.ConclusionsSupernormal 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).

Splenic Sequestration in Febrile Pediatric Sickle Cell Disease Patients

Introduction: Acute splenic sequestration is a rare complication of pediatric sickle cell disease (SCD). Acute splenic sequestration crisis (ASSC) is characterized by an acute decrease in hemoglobin and is associated with an increased risk for hypovolemic shock, often requiring blood transfusion during acute episodes and splenectomy to prevent recurrent episodes. Recent studies have also shown that chronic splenomegaly and resultant anemia (described as chronic or subacute sequestration) with potential benefit of splenectomy. However, non-life-threatening splenic sequestration in febrile, hospitalized children with SCD is a frequent occurrence that has not been well-described in current literature. Aim: To estimate the change in WBC, Hemoglobin, platelet count from inpatient and outpatient baseline to lowest recorded value (LRV) for each febrile hospitalization in sickle-cell disease patients while controlling for hydroxyurea use and patient age. Methods: A retrospective chart review was performed on febrile, hospitalized children with a diagnosis of SCD who presented to a tertiary care hospital from 2018-2021. Data including the magnitude of fever, presence of splenomegaly and trends in laboratory parameters such as complete blood count, and chemistries were recorded. Demographics, hydroxyurea use, transfusions and sickle cell phenotype were also recorded. For our primary outcome we estimated the change in Hgb, platelets, and WBC count from inpatient (first day of hospitalization) and outpatient (most recent outpatient values) baselines to the lowest recorded value (LRV) for each hospital encounter. We employed mixed models to account for within-subject correlation and adjusted for hydroxyurea use and categorized patient age. The beta coefficient and corresponding 95% confidence interval (CI) were reported for the model intercept and predictors. Results: Sixty-six unique patients (ages 0-17) accounted for a total of 117 hospital encounters. There was a statistically significant drop in WBC per microliter (-5.40, 95% CI: -6.89 - [-3.91]) , Hgb g/dL (-0.95, 95% CI : -1.25 - [-0.66]), and platelets per microliter (-60.95, 95% CI : -83.18 - [-38.71]) from the inpatient baseline to the LRV. There was a statistically significant drop in estimated Hgb g/dL (-1.83, 95% CI : -2.23 - [-1.42]) and platelets per microliter (-130.50, CI: -169.59 - [-91.41]) from outpatient baseline to the LRV. Hospital encounters with hydroxyurea had a significantly greater drop in estimated platelets per microliter from inpatient baseline to LRV (-54.43 CI : -93.64 - [-15.22]) but significantly greater increase in estimated Hgb g/dL from inpatient baseline to the LRV (1.11 CI : 0.45 - 1.78) compared to hospital encounters without hydroxyurea. Hospital encounters over the age of 8 were associated with a significantly greater decrease in HGB g/dL (-0.59 CI : -1.04 - [-0.14]) from inpatient baseline to the LRV compared to hospital encounters under the age of 8. Conclusion: Our study demonstrated features consistent with acute, non-life-threatening splenic sequestration in febrile pediatric SCD patients, as evidenced by a statistically significant drop in platelets, Hgb, and WBC count from the inpatient baseline. The largest acute drop was observed in platelets, which presents the strongest argument for sequestration, as drops in Hgb may be explained by rehydration or hyperhemolysis, and changes in WBC count may be related to infection. Hydroxyurea use may delay auto-infarction of the spleen, thus predisposing to splenic sequestration at an age later than classically associated with sequestration. The preservation of splenic function probably explains greater decrease in platelet count for patients on hydroxyurea. Our study has treatment implications: children with SCD experiencing non-life-threatening acute splenic sequestration recover spontaneously without the need for blood transfusion in many cases, thus avoiding long-term complications such as RBC alloimmunization or iron overload. Also, as the drop in WBC, hemoglobin, and platelets are not due to myelosuppression, they should not lead to modification of hydroxyurea therapy. Splenectomy should be reserved for the most severe and life-threatening episodes of sequestration. Further research may assist in correlating sickle cell phenotype and history of blood transfusion with the magnitude of sequestration in this population.

Characteristics and Trends of Hospitalizations for Sickle-Cell Related Complications

Introduction There are approximately 100,000 people living with sickle cell disease (SCD) in the United States. As per the Center for Disease Control estimates, almost all patients with SCD will require hospitalization more than once a year and visit the emergency department at least 2-3 times a year on average. Previous studies have shown that SCD hospitalization trends are steadily increasing in the country. In November of 2019, two new drugs, crizanlizumab (to decrease the frequency of vaso-occlusive crises) and voxelotor (to increase hemoglobin response), were approved by the Food and Drug Administration (FDA) for the treatment of sickle cell disease. Around the same time, the entire health care system experienced disruption in the form of the COVID-19 pandemic. Hence, we conducted this retrospective study to assess SCD hospitalization trends from 2016-2020 and stratified them across various demographic factors to analyze the underlying causes. Methods We conducted a retrospective study from the National Inpatient Sample (NIS), which is a large all-payer database created by the Health Care Cost and Utilization Project (HCUP). We included all adult patients with a diagnosis of SCD (HbSS, HbSC, Sickle/b thal, and other variants) and identified their trends of hospitalizations for various SCD-related complications like vaso-occlusive crises, heart failure exacerbation, acute kidney injury, stroke, sepsis with and without septic shock, bacteremia, pneumonia, osteomyelitis, acute chest syndrome, splenic sequestration, and priapism. We then did a linear-to-linear analysis and ANOVA test to stratify these trends across various age, gender, income, and location groups. SPSS was used for the statistical analysis. Results Our study included a total of 19,250 patients who had at least one admission for sickle cell-related complications during 2016-2020. The average number of admissions for sickle cell pain crisis steadily increased from 10.2 per 100,000 in 2016 to 14.7 in 2019 and then decreased to 13.9 in 2020. Priapism steadily declined from 2.3% in 2016 to 1.4% in 2020 (p&amp;lt;0.001). Acute kidney injury complicated 4.9% of admissions in 2016 and steadily rose to 5.2% of admissions in 2020 (p = 0.88). Admissions complicated by bacteremia peaked in 2017 (0.9%) but have since been on a decline (0.5% in 2020) (p-0.02). Admissions complicated by pneumonia showed a steady decline from 6% in 2016 to 4.3% in 2020 (p&amp;lt;0.001). Admissions with osteomyelitis, splenic sequestration, acute chest syndrome, heart failure exacerbation, stroke, and sepsis complicated &amp;lt;1% of all admissions and were not statistically relevant. When stratified by age, it was noted that the age group of 18-39 had the most admissions. Females consistently had more admissions than males. Medicaid was the predominant insurance among all the admissions, followed by Medicare. Around 50% of the patients admitted for SCD-related complications were in the 0-25th percentile of median household income quartiles. The majority of admissions were seen in urban teaching hospitals. The majority of these admissions were also seen in the Southern regions. Conclusion Our results show that female patients in the age group 18-39 years, those covered by Medicaid and Medicare, and those in lower income quartiles comprised the majority of admissions for SCD-related complications. This demonstrates disparities in SCD care, wherein patients in lower socio-economic strata may not have access to newer advances in SCD treatment. Although it is optimistic to note that admissions for pain crises had a significant decline from 2019-2020, it remains to be seen whether these numbers are due to new therapies or due to the disruption of healthcare services caused by the pandemic. Analyzing more long-term trends after the year 2020 will help us understand this impact. The overall trend of infections and sepsis has been low, likely due to widespread vaccinations and early antibiotic treatments. It is interesting to note that although there was a downtrend for the majority of SCD complications, the incidence of AKI during admissions is steadily rising, validating the need to focus more on renal care in sickle cell patients.