Sickle Cell Disease Patients Research Articles

The Influence of Demographic and Insurance Factors on Hospitalization Rates, Treatment Costs, and Length of Stay for Sickle Cell Disease Patients among African Americans

The Influence of Demographic and Insurance Factors on Hospitalization Rates, Treatment Costs, and Length of Stay for Sickle Cell Disease Patients among African Americans

Length of Stay, Readmission Rates, and Mortality Are Similar Between Hospitalized Individuals With Sickle Cell Disease With and Without COVID-19.

Background We sought to clarify the impact of COVID-19 on clinical outcomes in sickle cell disease patients, given their baseline hypercoagulable state in combination with COVID-19-related coagulopathies and other complications. Methods Retrospective chart review of two groups of sickle cell disease patients hospitalized between March 2020 to December 2021: Group 1 did not have COVID-19 (n = 95) and Group 2 did (n = 73). Results Groups 1 and 2 were similar in terms of age, race, sex, comorbid illnesses, genotype, hydroxyurea use, and opioid use. Group 1 and 2 patients had a mean hospital length of stay of 7.05 and 7.64 days, respectively (p = 0.981). ICU-level care was required for six (6.3%) Group 1 patients and four (5.5%) Group 2 patients (p = 1.000). Readmissions within 30 days occurred for 25 (26.3%) Group 1 patients, and 18 (24.7%) Group 2 patients (p = 0.807). Death occurred for one (1.05%) Group 1 patient and one (1.4%) Group 2 patient (p = 1.000). There were no significant differences in commonly ordered initial laboratory values (total bilirubin, hemoglobin, hematocrit, creatinine, lactate dehydrogenase, and D-dimer) between Group 1 and Group 2 patients. Conclusions We observed no significant differences in clinical outcomes among sickle cell disease patients hospitalized due to COVID-19 compared to those without COVID-19.

A contemporary evaluation of the frequency & factors associated with overt stroke across the lifespan: A Ghanaian sickle cell disease registry analysis

BackgroundStroke is a devastating complication of Sickle Cell Disease (SCD) with significant mortality and substantial morbidity. The burden of prevalent stroke in SCD is highest in sub-Saharan Africa and estimated at 4.2 % to 6.4 % in the era where evidence-based prevention strategies such as use of hydroxyurea therapy and transcranial doppler ultrasound were not routine care. PurposeTo assess the contemporary frequency and factors associated with prevalent stroke across the lifespan in an SCD registry at the tertiary medical center in Ghana. MethodsThis is a cross-sectional study conducted at the Komfo Anokye Teaching Hospital, a tertiary medical center in the middle belt of Ghana. The center has comprehensive Sickle Cell Clinics for children, adolescents, and adults with a patient registry established as part of the Sickle Pan-African Research Consortium (SPARCo)-Ghana study from 2017 to date. Data captured in the registry and analyzed for the present study include demographics, stroke status using the WHO criteria supplemented by the Questionnaire for Verifying Stroke Free Status (QVSFS), use of hydroxyurea, and complete blood count. Logistic regression modeling was utilized to assess factors associated with stroke. ResultsAmong a registry cohort of 4115 individuals with confirmed SCD, 35 (0.85 %, 95 % CI: 0.59–1.18 %) had overt or clinically confirmed stroke. The frequency of stroke differed significantly across the lifespan being 0.38 % (95 % CI: 0.12–0.64 %) among children <10 years, 1.23 % (95 % CI: 0.73–1.94 %) among adolescents aged 10 to 17 years, and 1.44 % (95 % CI: 0.66–2.71 %) among adults 18 years or more, p = 0.007. In adjusted analysis, each 10-year increase in age was associated with odds ratio, OR (95 % CI) of 1.90 (1.42–2.54) and hydroxyurea use, OR of 6.09 (2.65–13.99). The association between hydroxyurea and stroke observed in this cross-sectional study is not causal. ConclusionApproximately 1 in 120 SCD patients in this large Ghanaian cohort had clinically overt stroke. The gradual uptake of hydroxyurea therapy into routine care for SCD in this resource-limited setting, may partly explain the lower frequency of stroke.

Long-term outcomes of avascular necrosis in sickle cell disease using joint-specific patient-reported outcome measures: Results from a multicentre study.

Avascular necrosis (AVN) is a prevalent and progressive complication in young patients with sickle cell disease (SCD), but no study evaluated the long-term subjective and objective outcome measures. Oxford hip score (OHS) and Oxford shoulder scores (OSS) are validated joint-specific patient-reported outcome measures (PROMs). In this prospective multicentre study, 47 SCD patients with pre-existing diagnosis of AVN occurred at a median age of 35.9 (24.2-47.6) filled out the OHS and OSS at median follow-up of 9.4 years (4.5-12.9). No patient died after diagnosis of AVN. Hip AVN was present in 34 (72%) patients, with bilateral involvement in 25 (74%); 26 (59%) underwent total hip arthroplasty (THA) at a median age of 34.6 (22.6-49.5); and 4 (15%) required re-surgery. OHS revealed moderate to severe impairment both in patients underwent THA and no hip surgery. Shoulder AVN was present in 13 (6%) patients and OSS revealed mild to moderate impairment. A high rate of compromised joint function and pain was observed 10 years after diagnosis of AVN regardless of the type of treatment, outlying the need to improve the management of this sickle-related complication. OHS and OSS are validated joint-specific PROMs easy to use in all SCD centres.

Multicenter comparative study of polysomnography outcomes in children with the monogenic disorder sickle cell disease.

Sleep-disordered breathing (SDB) is prevalent in children with sickle cell disease (SCD) and is associated with worse outcomes. This study aims to compare the outcomes of polysomnography (PSG) performed for pediatric patients with SCD at three United States centers. We included children with SCD aged 0-21 who underwent PSG at three American Academy of Sleep Medicine accredited centers: the University of Alabama at Birmingham (UAB), the University of Florida (UF), and Duke University Hospital (DUH), between 2012 and 2022. Descriptive statistics were used as appropriate to compare the baseline characters and PSG outcomes among the different centers. A total of 210 children with SCD from the three centers were included, with comparable sex, SCD genotypes, hemoglobin, hematocrit levels, and chronic transfusion. Children from the different centers exhibited variations in age (P < .001), BMI (P < .05), mean corpuscular volume (P < .05), and hydroxyurea use (P < .05) at the time of the PSG. Overall, the three centers showed significantly different PSG outcomes. Patients from UF had worse obstructive sleep apnea, oxygenation, and periodic leg movement events, together with lower hydroxyurea usage. While those from DUH showed higher hypoventilation and arousal indices. This multicenter study underscores variations in PSG outcomes among pediatric SCD patients at different centers in the Southeast United States. These findings emphasize the need for standardized approaches to screen for SDB, refer to PSG, and interpret the results in children with SCD. These conclusions may apply to other genetic disorders associated with an increased risk of sleep-disordered breathing.

GBT1118, a Voxelotor Analog, Ameliorates Hepatopathy in Sickle Cell Disease.

Background and Objectives: In sickle cell disease (SCD), hepatopathy is a cumulative consequence of ischemia/reperfusion (I/R) injury from a vaso-occlusive crisis, tissue inflammation, and iron overload due to blood transfusion. Hepatopathy is a major contributing factor of shortened life span in SCD patients. We hypothesized that the voxelotor, a hemoglobin allosteric modifier, ameliorates sickle hepatopathy. Materials and Methods: Townes SCD mice and their controls were treated with either chow containing GBT1118, a voxelotor analog, or normal chow. We evaluated inflammation, fibrosis, apoptosis and ferroptosis in their livers using qPCR, ELISA, histology, and immunohistochemistry. Results: GBT1118 treatment resulted in reduced hemolysis, iron overload and inflammation in the liver of SCD mice. There were significant reductions in the liver enzyme levels and bile acids. Furthermore, GBT1118-treated mice exhibited reduced apoptosis, necrosis, and fibrosis. Increased ferroptosis as evident from elevated 4-hydroxynonenal (4-HNE) staining, malondialdehyde (MDA) levels, and expression of Ptgs2 and Slc7a11 mRNAs, were also significantly reduced after GBT1118 treatment. To explain the increased ferroptosis, we evaluated iron homeostasis markers in livers. SCD mice showed decreased expression of heme oxygenase-1, ferritin, hepcidin, and ferroportin mRNA levels. GBT1118 treatment significantly increased expressions of these genes. Conclusions: Our results suggest GBT1118 treatment in SCD confers the amelioration of sickle hepatopathy by reducing inflammation, fibrosis, apoptosis, iron overload and ferroptosis.

Vestibular Dysfunction in Patients With Sickle Cell Disease: A Systematic Review.

Sickle cell disease (SCD) often leads to sensorineural hearing loss due to vaso-occlusive events in the cochlear vasculature. Although the vestibule and cochlea share a blood supply, information on vestibulopathy in SCD is limited. This systematic review aims to consolidate current knowledge on vestibular dysfunction in SCD patients. This study, registered on PROSPERO, involved a thorough electronic search using MEDLINE-Ovid, Embase, Google Scholar, The Cochrane Library, and Scopus databases from inception to December 2023. Data extraction adhered to PRISMA guidelines. Authors independently assessed bias and evidence quality using NIH Study Quality Assessment tools. Inclusion criteria covered articles mentioning vestibular symptoms in SCD patients, whereas exclusion criteria comprised non-English articles and vestibular symptoms limited to treatment side effects. Out of 2,495 studies, only 12 met the criteria. Among SCD patients undergoing head imaging, 19% reported inner ear complaints, and 70% experienced dizziness/imbalance. In a group of SCD children, there was a significant relationship between endothelial dysfunction and vertigo duration. The recommended imaging sequence was T1-weighted thin-section temporal bone MRIs, which revealed abnormal findings even without clinical symptoms. Imaging showed labyrinthine hemorrhage and labyrinthitis ossificans, mostly unilateral. Vestibular symptoms emerged with older age, suggesting cortical compensation kept most subjects asymptomatic. In asymptomatic adult SCD patients, there was no significant difference compared with controls in tracking test batteries and positional tests; however, saccadic latency was longer in SCD patients. The existing data on vestibulopathy in SCD were limited and often of poor quality. Although a connection between SCD and vestibular symptoms was noted, information on treatment approaches was scant. Further research in this area could contribute to the early diagnosis of vestibular dysfunction, potentially enhancing outcomes for SCD patients.

Impaired microvascular function in patients with sickle cell anemia and leg ulcers improved with healing.

Leg Ulcer (LU) pathophysiology is still not well understood in sickle cell anaemia (SCA). We hypothesised that SCA patients with LU would be characterised by lower microvascular reactivity. The aim of the present study was to compare the microcirculatory function (transcutaneous oxygen pressure (TcPO2) on the foot and laser Doppler flowmetry on the arm) and several blood biological parameters between nine SCA patients with active LU (LU+) and 56 SCA patients with no positive history of LU (LU-). We also tested the effects of plasma from LU+ and LU- patients on endothelial cell activation. We observed a reduction of the TcPO2 in LU+ compared to LU- patients. In addition, LU+ patients exhibited lower cutaneous microvascular vasodilatory capacity in response to acetylcholine, current and local heating compared to LU- patients. Inflammation and endothelial cell activation in response to plasma did not differ between the two groups. Among the nine patients from the LU+ group, eight were followed and six achieved healing in 4.4 ± 2.5 months. Among thus achieving healing, microvascular vasodilatory capacity in response to acetylcholine, current and local heating and TcPO2 improved after healing. In conclusion, microcirculatory function is impaired in patients with LU, and improves with healing.

A Study of the Clinical Profile of Iron Deficiency Anemia in Children With Sickle Cell Disease in a Tertiary Care Center.

Background Sickle cell disease (SCD) and iron deficiency anemia (IDA) are significant global health concerns, particularly in pediatric populations. This study investigates the prevalence, clinical impact, and management challenges of IDA in children with SCD. Methods A prospective observational study was conducted at the Department of Pediatrics, Jawaharlal Nehru Medical College(JNMC) and Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi, from June 2022 to May 2024. The study included 60 children diagnosed with SCD. Comprehensive assessments were performed, including medical histories, physical examinations, and hematological investigations. Diagnosis of IDA was based on hemoglobin levels, mean corpuscular volume (MCV), red cell distribution width (RDW), peripheral blood smears, serum iron levels,and serum ferritin concentrations. Results Of the 60 participants, 15% exhibited iron deficiency. No significant gender differences were found in iron deficiency status. A significant association was observed between SCD type and the presence of pallor (p = 0.025) and sickle cell crises (p = 0.023). The study also found no significant association between SCD type and the presence of organomegaly (p = 0.079) or iron deficiency status (p = 0.675). The mean hemoglobin levels varied across SCD types, with sickle cell anemia patients showing lower levels than those with sickle cell trait or disease. Conclusion Diagnosing and managing IDA in children with SCD is complex due to overlapping hematological features and the risk of iron overload from frequent transfusions. Tailored diagnostic and therapeutic approaches are essential to improving hemoglobin levels, reducing complications, and enhancing the quality of life for affected children. This study provides valuable insights for refining clinical practices and emphasizes the need for a multidisciplinary approach to managing these intertwined conditions.

Black Americans With Sickle Cell Disease (SCD) Demonstrate Accelerated Epigenetic Pace of Aging Compared to Black Americans Without SCD.

Sickle cell disease (SCD) is a chronic medical condition characterized by red blood cell sickling, vaso-occlusion, hemolytic anemia, and subsequently, end-organ damage and reduced survival. Because of this significant pathophysiology and early mortality, we hypothesized that patients with SCD are experiencing accelerated biological aging compared with individuals without SCD. We utilized the DunedinPACE measure to compare the epigenetic pace of aging in 131 Black Americans with SCD to 1391 Black American veterans without SCD. SCD patients displayed a significantly accelerated pace of aging (DunedinPACE mean difference of 0.057 points) compared with the veterans without SCD, whereby SCD patients were aging ≈0.7 months more per year than those without SCD (p = 4.49 × 10-8). This was true, even though the SCD patients were significantly younger according to chronological age than the individuals without SCD, making the epigenetic aging discrepancy even more apparent. This association became stronger when we removed individuals with posttraumatic stress disorder from the non-SCD group (p = 2.18 × 10-9), and stronger still when we restricted the SCD patients to those with hemoglobin SS and Sβ0 thalassemia genotypes (p = 1.61 × 10-10). These data support our hypothesis that individuals with SCD experience accelerated biological aging as measured by global epigenetic variation. The assessment of epigenetic measures of biological aging may prove useful to identify which SCD patients would most benefit from clinical interventions to reduce mortality.

Buprenorphine: Opioid Agonist-Antagonist for Refractory Pain of Sickle Cell Disease Patients During Hematopoietic Stem Cell Transplant, Uncontrolled By Full-Agonist Opioids.

Bone marrow transplant (BMT) offers potential cure for cancer and a spectrum of otherwise incur- able diseases. The BMT process can cause multi-systemic pain in patients with sickle cell disease (SCD) refractory to high-dose opioid analgesics during BMT because of their pre-existing opioid-tolerance. Because of frequent pain resulting in hyperalgesia and chronic opioid use, SCD patients undergoing BMT often experience excruciating pain uncontrolled by exceedingly high-dose opioids with severe and intolerable adverse effects. There is a small but growing body of literature about the successful buprenorphine effect for SCD's chronic pain management that had failed sufficient pain relief by the traditional full-agonist opioids in the outpatient setting. However, the buprenorphine use for acute inpatient pain management has not been previously researched. Pilot prospective clinical trial with buprenorphine-based pain management for acute BMT-related pain was initiated for SCD patients' pain uncontrolled by full-agonist opioids. Procedures/data/observations: Buprenorphine was started as scheduled and as-needed analgesics, supplemented by full-agonist opioids upon consultation for uncontrolled BMT-related pain of SCD patients. Patients' 24-hour opioid requirement by morphine equivalent daily doses (MEDD) were assessed at 3 time points: 1)immediately before pain escalation; 2)consultation; 3)discharge. MEDDs were compared to those of patients treated with full-agonist opioids only. Cases treated by full-agonist opioids (morphine/hydromorphone/fentanyl/methadone/oxycodone) had MEDD escalation by 1230-16300% by discharge compared to immediately before BMT-related pain escalation. Buprenorphine-supported cases had significantly smaller MEDD increase by 220-317%. Our case series suggests superior pain control by adding Buprenorphine prior to opioid dose escalation during BMT for SCD. Buprenorphine may provide the advantageous effect for other patients with complex pain background and experiencing difficult pain management during BMT due to pre-existing hyperalgesia and high opioid-tolerance. The evidence for buprenorphine's analgesic effect is moderate but growing, and more randomized controlled trials comparing the buprenorphine and other standard opioids are needed.

Outcome of Pediatric Patients With Sickle Cell Anemia Admitted With Fever: A Retrospective Single-Center Study.

Pediatric patients with sickle cell anemia (SCA) are known to have an increased susceptibility to infections, leading to a higher incidence of fever among this population. However, there is limited literature specifically focusing on the outcomes of pediatric SCA patients presenting to the emergency department (ED) or hospital with a primary diagnosis of fever. The objective of this retrospective single-center study was to compare the characteristics of fever and associated symptoms among pediatric patients with SCA, and to investigate the risk factors associated with patients' outcomes and mortality in this specific population. The study was conducted at the King Salman Medical City, Maternity and Children's Hospital, Medina, Saudi Arabia, during the period from 2017 to 2022. All pediatric SCA patients under the age of 14, who presented to the ED of the hospital during the study period with a primary diagnosis of fever, were included. The study collected and analyzed clinical, laboratory, treatment, complications, and outcome data of the patients using appropriate statistical methods, including logistic regression. A total of 57 children were included in the analysis. The mean age of the patients was 7.1 ± 4.3 years, with 26 males (45.6%) and 31 females (54.4%). Among the cases, 8 (14%) exhibited fever along with gastrointestinal symptoms, 18 (31.6%) presented with musculoskeletal symptoms, 5 (8.8%) showed neurological symptoms, and approximately half of the cases (45.6%) displayed respiratory symptoms along with fever. Logistic regression analysis identified several significant factors associated with complications in this sample, including a very low level of hemoglobin (Hb) (<7 g/dL) with an odds ratio (OR) of 14.5 (95% CI=1.03-222.3), ICU admission with OR of 14 (95% CI=1.03-186.8), and a hospital stay duration of more than 10 days (OR=11.5; 95% CI=1.10-121.3). Additionally, fever associated with neurological symptoms, neutrophilia, history of splenectomy, and male sex showed positive associations with complications among the studied patients, although not significant. This study provides valuable insights into the characteristics and outcomes of febrile pediatric patients with SCA. The findings highlight the importance of early recognition and management of fever in this vulnerable population, particularly when certain risk factors are present.

Access to Allogeneic Cell Transplantation Based on Donor Search Prognosis: An Interventional Trial.

Patients requiring allogeneic hematopoietic cell transplantation have variable likelihoods of identifying an 8/8 HLA-matched unrelated donor. A Search Prognosis calculator can estimate the likelihood. To determine if using a search algorithm based on donor search prognosis can result in similar incidence of transplant between patients Very Likely (>90%) vs Very Unlikely (<10%) to have a matched unrelated donor. This interventional trial utilized a Search Prognosis-based biologic assignment algorithm to guide donor selection. Trial enrollment from June 13, 2019-May 13, 2022; analysis of data as of September 7, 2023 with median follow-up post-evaluability of 14.5 months. National multi-center Blood and Marrow Transplantation Clinical Trials Network 1702 study of US participating transplant centers. Acute myeloid and lymphoid leukemias, myelodysplastic syndrome, Hodgkin's and non-Hodgkin's lymphomas, severe aplastic anemia, and sickle cell disease patients referred to participating transplant centers were invited to participate. 2225 patients were enrolled and 1751 were declared evaluable for this study. Patients were declared evaluable once it was determined no suitable HLA-matched related donor was available. Patients assigned to the Very Likely arm were to proceed with matched unrelated donor, while Very Unlikely were to utilize alternative donors. A third stratum, Less Likely (∼25%) to find a matched unrelated donor, were observed under standard center practices, but were not part of the primary objective. Cumulative incidence of transplantation by Search Prognosis arm. Evaluable patients included 1751 of which 413 (24%) were from racial/ethnic minorities. Search prognosis was 958 (55%) Very Likely, 517 (30%) Less Likely and 276 (16%) Very Unlikely. 1171 (67%) received HCT, 384 (22%) died without HCT, and 196 (11%) remained alive without HCT. Among the 1,234 patients, the adjusted cumulative incidence (95% CI) of HCT at 6-months was 59.8% (56.7-62.8) in the Very Likely group versus 52.3% (46.1-58.5) in the Very Unlikely (P=0.113). A prospective Search Prognosis-based algorithm can be effectively implemented in a national multicenter clinical trial. This approach resulted in rapid alternative donor identification and comparable rates of HCT in patients Very Likely and Very Unlikely to find a matched unrelated donor. Trial Registration: NCT#03904134.

Clinical Outcomes of Sickle Cell Disease Patients With Myocardial Infarction Undergoing Percutaneous Coronary Intervention: A Nationwide Analysis.

Sickle cell disease (SCD) patients are predisposed to various cardiovascular complications due to the nature and progression of the disease; the clinical outcomes of SCD patients experiencing myocardial infarction (MI) and undergoing percutaneous coronary intervention (PCI) are not well known. This study aims to explore a comprehensive nationwide analysis of the clinical outcomes in SCD patients who have suffered an MI and subsequently undergone PCI. Italso identifies potential complications and compares their outcomes with non-SCD counterparts with the same interventions. We conducted a retrospective analysis of SCD patients who have suffered an MI and subsequently undergone PCI using the National Inpatient Sample (NIS) database from 2016 to 2020. The primary outcome was mortality, while the secondary outcomes were the average length of stay, comorbid conditions, and cardiovascular outcomes. Logistic, linear, and Poisson regression model analysis applied for outcomes and adjusting co-founders. P-value <0.05 was considered significant. A total of 775 patients were analyzed for MI who had PCI with SCD, with a mean age of 58±1.06years. SCD patients exhibited higher rates of comorbidities, including diabetes mellitus (45.81% vs. 37.84%), obesity (23.87% vs. 20.85%), and chronic kidney disease (CKD) (29.03% vs. 17.36%). Heart failure was more common among SCD patients with 34.19% vs. 26.02% in non-SCD patients(OR 1.5, CI 1.1-2.1, p-value=0.02). Other cardiovascular complications such as stroke, ventricular arrhythmias, atrial fibrillation, pulmonary edema, cardiogenic shock, cardiac arrest, and mortality did not significantly differ betweenSCD and non-SCD(P-values >0.05). The study observed that SCD patients experienced a significantly higher incidence of heart failure than non-SCD patients. This implies that SCD patients undergoing PCI for MIexhibit distinct clinical outcomes compared to their non-SCD counterparts.

Genetic variants associated with white blood cell count amongst individuals with sickle cell disease.

Sickle cell disease (SCD) is a Mendelian disorder characterized by a point mutation in the β-globin gene that leads to sickling of erythrocytes. Several studies have shown that absolute neutrophil count is strongly associated with clinical severity of SCD, suggesting an apparent role of white blood cells (WBC) in SCD pathology. However, the mechanism by which genetic variants lead to WBC count differences in SCD patients remains unclear. Genome-wide association (GWA) analyses were carried out amongst a cohort of 2409 Brazil SCD participants. Association of WBC count and genetic markers were investigated in homozygous sickle cell anaemia participants and compound heterozygous sickle cell haemoglobin C participants. GWA analysis showed that variants in genes TERT, ACKR1, and FAM3C are associated with WBC count variation. The well-studied association between WBC count and Duffy null phenotype (variant in ACKR1) in healthy populations was replicated, reinforcing the influence of the SNP rs2814778 (T>C) in WBC count. Genetics plays an important role in regulating WBC count in patients with SCD. Our results point to possible mechanisms involved in WBC count variation and as increased WBC count is associated with more severe SCD, these results could suggest potential therapeutic targets for individuals with SCD.

Design and Implementation of a Sickle Cell Disease Electronic Registry in Resource Limited Setting in Nigeria—A Pilot Study

Background: Sickle cell disease (SCD) is an autosomal recessive haemoglobin disorder, affecting about 7.74 million individuals worldwide, but it is more prevalent among Africans and Asians. SCD is characterised by many complications, and it is a major health issue in Nigeria, the country with the largest burden of the disease globally. This work aims to present the design and implementation of electronic registries (ER) for SCD in a tertiary hospital in Nigeria. Methods: Registry design was initiated during a staff exchange programme within the ARISE initiative (EU grant agreement no. 824021). Ethical approval was obtained, and paper records were retrieved and transferred into one adult and one paediatric database, developed with Microsoft Access. Results: Data from 2659 SCD patients were entered in the ERs, including 698 (26.3%) adults and 1961 (73.7%) children. There were 287 (41%) male adults, 404 (58%) female and 7 (1%) patients whose gender was missing. There were 1041 (53.1%) male children, 906 (46.2%) female and 14 (0.7%) whose gender was missing. Information on phenotype was available for 2385 subjects, and most of them (2082, 87.3%) were SS. The most prevalent SCD-related complication was painful events (26.6% in adults and 68.7% in children, considering valid cases). Conclusions: About 60% of SCD patients in the centre were included in the ERs providing useful, hands-on recommendations for future ER design in SCD. These ERs might be an appropriate tool for collecting and analysing SCD patients’ data.

A - 87 Exploring the Utility of the Montreal Cognitive Assessment to Identify Neurocognitive Deficits among Adult Patients with Sickle Cell Disease

Abstract Objective Neurocognitive deficits associated with sickle cell disease (SCD) have been well established in the pediatric population but studies examining the adult neurocognitive profile are lacking. This study examined the utility of the Montreal Cognitive Assessment (MoCA) to screen patients for cognitive impairments within a multidisciplinary adult sickle cell clinic. Method Patients who presented to their scheduled appointment at the UCSF Benioff Children’s Hospital Oakland Adult Sickle Cell Clinic were provided psychoeducation and offered neurocognitive screening. Those that accepted completed a brief clinical interview and were screened with the MoCA by neuropsychology externs or a licensed clinical psychologist. Results A sample of 24 patients (M age = 37.63, age range = 18–75; female =58.33%) were screened with the MoCA. Of patients screened, 41.67% (n = 10) were identified as mildly impaired (M score = 22) and 16.67% (n = 4) were identified as moderately impaired (M score = 15.5), consistent with other studies in the literature. Overall MoCA score and the memory subdomain were both negatively correlated with increasing age (r = −0.15, p &amp;lt; 0.05 and r = −0.06, p &amp;lt; 0.05 respectively). Conclusions Utilizing the MoCA, our study demonstrates a notable prevalence of cognitive impairment identified in 58.43% of adult SCD patients, with a marked decline associated with advancing age. These findings suggest the MoCA’s utility; however, further research is needed to understand the validity of this measure in detecting the varying levels of cognitive impairment in adult SCD patients. Such measures could significantly enhance the care and quality of life for individuals with SCD and address age disparities in SCD, where resources for adult patients are much more limited.

Secretory Phospholipase A2 as a Promising Biomarker for Predicting Acute Chest Syndrome in Children With Sickle Cell Disease: A Systematic Review and Meta-Analysis.

Acute chest syndrome (ACS) is a severe and potentially life-threatening complication of sickle cell disease (SCD). Early identification of patients at risk for ACS is crucial for timely intervention. There is a potential association between ACS and elevated levels of secretory phospholipase A2 (sPLA2), an enzyme involved in the breakdown of phospholipids. sPLA2 has emerged as a promising biomarker for predicting ACS. This systematic review and meta-analysis aimed to assess the diagnostic value of PLA2 in predicting ACS among children with SCD. A comprehensive search was conducted across multiple databases, including MEDLINE, Embase, Cochrane Library, PubMed, and Web of Science. Studies assessing the relationship between sPLA2 levels and ACS in SCD patients were included. Pooled sensitivity, specificity, likelihood ratios, and the area under the receiver operating characteristic curve (AUC) were calculated to assess sPLA2's diagnostic accuracy. There is a potential association between significant association between elevated sPLA2 levels and increased ACS risk in SCD patients. The pooled sensitivity of sPLA2 for predicting ACS was 0.766 (95% CI: 0.620-0.877), with a pooled specificity of 0.736 (95% CI: 0.680-0.787). The AUC of the summary receiver operating characteristic (SROC) curve was 0.84, indicating good discriminatory ability. sPLA2 emerges as a promising biomarker for predicting ACS in SCD patients, potentially guiding risk stratification and early intervention strategies to enhance patient outcomes. Nonetheless, further prospective studies are warranted to validate its clinical utility and standardize sPLA2 assay protocols.

Detectability of white matter cerebral blood flow using arterial spin labeling MRI in patients with sickle cell disease: Relevance of flow territory, bolus arrival time, and hematocrit.

Sickle cell disease (SCD) is the most common genetic blood disorder, characterized by red cell hemolysis, anemia, and corresponding increased compensatory cerebral blood flow (CBF). SCD patients are at high risk for cerebral infarcts and CBF quantification is likely critical to assess infarct risk. Infarcts primarily localize to white matter (WM), yet arterial spin labeling (ASL) MRI, the most common non-invasive CBF approach, has poor WM CBF sensitivity owing to low WM CBF and long WM bolus arrival time (BAT). We hypothesize that anemia, and associated cerebral hyperemia, in SCD leads to improved WM detection with ASL. We performed 3-Tesla multi-delay pulsed ASL in SCD (n = 35; age = 30.5 ± 8.3 years) and control (n = 15; age = 28.7 ± 4.5 years) participants and applied t-tests at each inversion time within different flow territories, and determined which regions were significantly above noise floor (criteria: one-sided p < 0.05). Total WM CBF-weighted signal was primarily detectable outside of borderzone regions in SCD (CBF = 17.7 [range = 12.9-25.0] mL/100 g/min), but was largely unphysiological in control (CBF = 8.1 [range = 7.6-9.9)] mL/100 g/min) participants. WM BAT was reduced in SCD versus control participants (ΔBAT = 37 [range = 46-70] ms) and BAT directly correlated with hematocrit (Spearman's-ρ = 0.62; p < 0.001). Findings support the feasibility of WM CBF quantification using ASL in SCD participants for appropriately parameterized protocols.

Global awareness of antigenic peptides - Unraveling the impact on sickle cell anemia patients in the presence of pathogens: A narrative review.

Sickle cell anemia (SCA) is a genetic blood disorder characterized by the production of abnormal hemoglobin S (HbS), leading to sickle-shaped red blood cells and various complications, including increased susceptibility to infections. The presence of antigenic peptides, short amino acid sequences derived from pathogens or altered self-proteins, plays a crucial role in immune responses. This review explores the global awareness of antigenic peptides, their role in immune responses in SCA patients, and the challenges and opportunities in managing infections within this vulnerable population. Antigenic peptides are central to the adaptive immune response, facilitating the recognition and elimination of pathogens by T-cells. In SCA, altered antigen presentation and impaired T-cell responses due to chronic inflammation, functional asplenia, and ongoing hemolysis contribute to increased susceptibility to infections. Pathogens such as Streptococcus pneumoniae and Haemophilus influenzae pose significant risks to SCA patients, highlighting the importance of robust immune responses mediated by antigenic peptides. Strategies such as vaccination and immunotherapy aim to enhance immune function by targeting specific antigenic peptides, thereby reducing infection rates and improving patient outcomes. Advances in genomics and proteomics offer insights into individual variations in antigen presentation and immune responses, guiding the development of tailored therapeutic interventions. Global collaborations are essential to address disparities in healthcare access and implement effective preventive measures, ensuring equitable outcomes for SCA patients worldwide.