Sickle Cell Disease Patients Research Articles

Morbidity pattern and impact of hydroxyurea therapy among sickle cell patients in Raipur district of Chhattisgarh.

Sickle cell disease (SCD) is a disorder marked by a single-point mutation in the beta-globin gene. Hydroxyurea is a globally accepted disease-modifying agent that sounds to be effective in managing clinically and probably preventing complications of SCD. The current study aims to document the morbidity pattern and impact of Hydroxyurea therapy in the Outpatient Department of Sickle Cell Institute, Raipur. This cross-sectional study was conducted among randomly selected sixty-five patients (adults and children above six years). After obtaining informed consent, relevant data were collected in a predesigned pretested questionnaire. The appropriate statistical exercise was applied for the interpretation of results and inferences. Acute febrile illness 54 (83%) and 53 (81.5%) reported pain crisis observed to have the most common morbidity among the study subjects, followed by 55.4% (36), 33 (50.8%) jaundice and difficulty breathing, respectively. Joint pain was the most commonly observed complaint, particularly at the knee joint (76.9%). Other complaints such as hand-foot syndrome (24.6%), epistaxis (27.7%), and acute chest syndrome (21.5%). Vaso-occlusive crisis (72.4%), difficulty in walking (60.0%) and eyesight (35.4%), leg ulcers (9.2%), and dactylitis (3.1%) were also documented as clinical manifestations among study participants. Less than half (44.46%) had an awareness about SCD. Hydroxyurea therapy was highly significant in improving the patient's clinical picture (P < 0.01), especially following the frequency of hospitalization and the requirement for blood transfusion. Pain crisis is the most common morbidity among study participants with a low level of knowledge about SCD with febrile illness. Hydroxyurea therapy was found to be quite effective as a disease-modifying therapy, especially for reducing the frequency of blood transfusion and lowering hospitalization rates among SCD patients.

Time-restricted feeding does not improve nephropathy in humanized sickle cell disease mice

Sickle cell disease (SCD) is an autosomal recessive genetic disease caused by a point mutation in the hemoglobin gene. This substitution results in a “sickling” of red blood cells and subsequent vascular and organ damage. Current treatments, while increasing the lifespan of sickle cell patients, has resulted in a higher prevalence of chronic complications like SCD nephropathy. Our group has previously shown that time-restricted feeding (TRF) in chronic high fat fed mice reduces kidney damage. Given the increased kidney damage in SCD, we hypothesize that TRF in humanized SCD mice will attenuate sickle cell nephropathy. To test this hypothesis, we studied 18-22-week-old male SCD mice. Mice underwent 3 weeks of TRF, only having access to food during the active, dark period (Zeitgeber Time (ZT) 12 to 24). The control group had access to food ad libitum (ad-lib). At the end of the 3 weeks, at 21-25 week old ages, 12 hour urine was collected in metabolic cages as well as kidneys and plasma collection at ZT3 (inactive period). Excretion of urinary kidney damage markers (albumin and NGAL-1) showed no difference between TRF and ad-lib in both the active and inactive collection periods. Urinary excretion of endothelin-1 is known to be upregulated in SCD patients; however, TRF did not change this marker in SCD mice. TRF did not change plasma levels of cytokines or soluble adhesion molecules. Histological analysis of kidneys was conducted as an additional marker of kidney damage. We analyzed iron levels in the kidney with Prussian blue staining as well as fibrosis with Masson’s trichrome. TRF did not change kidney iron accumulation or kidney fibrosis. Immunohistochemical staining for CD3+ T cells did not show a difference in glomerular T cell infiltration in the TRF group compared to the ad-lib group. In conclusion, TRF does not appear to have an effect on renal inflammation or kidney function in SCD mice, but future studies need to be completed. R01 DK134562. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Predictive Factors for 30-Day Readmission and Increased Healthcare Utilization in Sickle Cell Disease Patients: A Single-Center Comparative Retrospective Study.

SCD poses a significant healthcare burden. Understanding the factors contributing to high healthcare utilization and readmissions is crucial for improving the quality of care provided. This retrospective comparative observational study was conducted at King Saud University Medical City and included 160 SCD patients. A comparison was made between patients with no readmission and patients with at least one 30-day readmission. Another comparison was done between high healthcare-utilizing patients and low healthcare-utilizing patients. A regression model for 30-day readmission prediction was created. Readmission was significantly higher in patients using opioids, following up with pain clinics, and having a history of AVN (p= 0.002, p=0.028 and p=0.025 respectively). Higher healthcare utilization was associated with older age, smoking, use of opioids and GABA analogs, and psychiatric illnesses, including depression, substance use disorder, and anxiety. Predictors of 30-day readmission were hydroxyurea use (odds ratio, 2.819 [95% CI,1.082 to 7.34], p = 0.034), follow-up with pain management clinics (odds ratio, 2.248 [95% CI,1.547 to 3.266], p = 0.001), and SCD genotype (SS genotype) (odds ratio, 1.754 [95% CI,1.012 to 3.042], p = 0.045). Using the Paracetamol/Codeine combination significantly reduced the likelihood of readmission within 30 days of discharge. This study identified factors associated with 30-day readmission rate and high healthcare utilization among SCD patients. Strategies to reduce readmissions may include specialized SCD clinics, educational programs for patients, improved physician awareness of mental health screening, and further research on the impact of opioid use. Limitations include retrospective nature, single-center design, reliance on self-reported data, and exclusion of critically ill patients. However, despite the limitations, this study could lay a foundation for future projects aiming to optimize care and outcomes for patients living with SCD.

Mildronate ameliorates kidney injury and reduces inflammation in Sickle Cell Disease mice

INTRODUCTION: Sickle cell disease (SCD) is a hereditary hemoglobin disorder characterized by hemolytic anemia, vaso-occlusive crisis and chronic inflammation that affects multiple organs including kidney, liver, brain, spleen, and heart. Renal disease, the most common complication in SCD, is a progressive disease that begins in childhood as glomerular hyperfiltration, then advances to albuminuria, following by a fast decline in glomerular filtration. It may further progress to a renal failure in adults. More than 50% of SCD patients develop chronic kidney disease (CKD), and 14-18% progress to the end-stage kidney disease. Renal injury in SCD results from a cascade of events starting with chronic red blood cells sickling and hemolysis leading to increased blood viscosity, microvascular obstruction and dilation, hypoxia in the medulla, oxidative stress, and inflammation. Mildronate (meldonium) is an anti-ischemic and anti-inflammatory medication approved in Eastern Europe. HYPOTHESIS: We hypothesized that mildronate administration reduces renal medullary hypoxia and decreases oxidative stress and inflammation ameliorating renal injury in SCD mice. METHODS: The study was approved by the Howard University IACUC. Townes SCD mice, expressing human HbS, and control mice, expressing human HbA, were injected with mildronate (400 mg/kg in saline) intraperitoneally or saline as vehicle control over the course of ten days. Blood was collected and used for hematological parameters analysis. Cytokines were measured by Bio-Plex suspension array in plasma. Hypoxyprobe Biotin kit (Hypoxyprobe Inc) was used for visualization of organ hypoxia. The effect of Mildronate on systemic and renal oxidative stress was measured by malondialdehyde (MDA) using ELISA (Abcam). Urinary KIM-1 was measured by TIM-1/KIM-1 ELISA kit (R&amp;D Systems). RESULTS: Mildornate injections did not affect hematological parameters of SCD mice including hematocrit, MCV, MCH, CMCH, erythrocytes and hemoglobin. Mildronate administration resulted in a significant reduction of the circulating pro-inflammatory cytokines IFN-γ, IL-1β and TNF-α and a trend toward reduction of IL-6, and IL-17 in SCD mice. We found higher level of hypoxia in the medulla of SCD mice compared to control mice. Mildronate injections did not reduced hypoxia in renal medulla of SCD mice. Also, mildronate injections did not change MDA levels in plasma or kidney of SCD mice. We found a significant reduction of proteinuria in SCD mice injected with mildronate compared to SCD mice injected with vehicle. Analysis of H&amp;E-stained kidneys showed significant reduction of glomerular size and medullar congestion areas in the mildronate injected SCD mice. Urinary KIM-1 levels were reduced by mildronate administration. CONCLUSIONS: Our results demonstrate that mildronate ameliorates glomerular and tubular injury in SCD mice and reduces capillary congestion. Mildronate improves renal function, in part by reducing inflammation but not through the reduction of hypoxia or oxidative stress. In future, we plan to assess the mildronate’s impact on kidney function and vessel inflammation. This work was supported by NIH grants R01HL125005, U54MD007597, and SC1HL150685. We thank Xiaomei Niu for helping with the Bio-Plex assay. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Insulin resistance and glucose homeostasis in Egyptian children with sickle cell anemia

Background A single gene mutation produces sickle cell anemia (SCA), an autosomal recessive illness. The body can keep the glycemic state in normal range via various mechanisms depending mainly on pancreatic hormones. Aim Evaluation of glucose homeostasis and insulin resistance in a group of Egyptian sickle cell children. Patients and methods This cross-sectional comparative study was carried out on 80 participants aged from 5 to 16 years old of both sexes, 40 patients with sickle cell hemoglobinopathies and in a steady state (case group), and 40 healthy individuals as control (control group). Fasting blood glucose, fasting serum insulin, glycosylated hemoglobin were measured in all participants, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated. Serum fructosamine (SF) was measured in the cases group. Results Glucose homeostasis was kept normal in most patients with only 10% of them showed abnormal glycemia. HOMA–IR was significantly different between the two groups with 15% of patients had pathological HOMA-IR. The study found a strong positive correlation (r=0.479, &lt;0.001) between the HOMA-IR and the frequency of vaso-occlusive crisis per year before participants were recruited and between SF and fasting blood glucose (r=0.772, &lt;0.001). On comparing glycosylated hemoglobin between both groups there was no statistically significant difference between both groups (P value = 0.874) Conclusions and recommendations Normal glucose homeostasis was proved in the majority of patients. Insulin resistance was detected in a limited number of sickle cell anemia patients. Follow-up of glucose homeostasis is indicated in sickle cell cases.

A miniaturized wash-free microfluidic assay for electrical impedance-based assessment of red blood cell-mediated microvascular occlusion

The production of HbS — an abnormal hemoglobin (Hb) — in sickle cell disease (SCD) results in poorly deformable red blood cells (RBCs) that are prone to microcapillary occlusion, causing tissue ischemia and organ damage. Novel treatments, including gene therapy, may reduce SCD morbidity, but methods to functionally evaluate RBCs remain limited. Previously, we presented the microfluidic impedance red cell assay (MIRCA) for rapid assessment of RBC deformability, employing electrical impedance-based readout to measure RBC occlusion of progressively narrowing micropillar openings. We describe herein the design, development, validation, and clinical utility of the next-generation MIRCA assay, featuring enhanced portability, rapidity, and usability. It incorporates a miniaturized impedance analyzer and features a simplified wash-free operation that yields an occlusion index (OI) within 15 min as a new metric for RBC occlusion. We show a correlation between OI and percent fetal hemoglobin (%HbF), other laboratory biomarkers of RBC hemolysis, and SCD severity. To demonstrate the assay’s versatility, we tested RBC samples from treatment-naïve SCD patients in Uganda that yielded OI levels similar to those from hydroxyurea (HU)-treated patients in the U.S., highlighting the role of %HbF in protecting against microcapillary occlusion independent of other pharmacological effects. The MIRCA assay could also identify a subset of HU-treated patients with high occlusion risks, suggesting that they may require treatment adjustments including a second-line therapy to improve their outcomes. This work demonstrates the potential of the MIRCA assay for accelerated evaluation of RBC health, function, and therapeutic effect in an ex vivo model of the microcapillary networks.

Clinical and Laboratory Features of Sickle Cell Disease S/D Punjab: Impact of HbF and Hydroxyurea.

Sickle cell disease (SCD) is a major public health issue worldwide with high morbidity and mortality. SCD SD Punjab is the third most common genotype of SCD in Oman and is associated with several serious complications. The aim of the study is to establish the clinical and laboratory features of SCD patients with SD double heterozygotes and study the impact of haemoglobin F, hydroxyurea, and other modulators on the disease severity. We analysed the electronic medical records of 52 consecutive SCD patients who were diagnosed as double heterozygote SD Punjab between 2006 and 2022. The study was approved by the local medical research and ethics committee. The data captured included SCD-related complications and current clinical and laboratory indices. Data from other studies on other SCD genotypes were used as historical controls. 52 patients (31 males, 21 females) who formed this cohort had a median age of 32 years with an interquartile range (IQR) of 21-39.8 years. 37(71.2%) had <3 VOC per year, whereas 15 (28.8%) patients had ≥3 vasooclusive (VOC) episodes per year. SCD-related complications included Acute Chest Syndrome (ACS) (48%), Gall stones (26.9%), Avascular necrosis (AVN) (28.8%), Stroke (13.5%) and splenic sequestration (7.7%), whereas 5 (9.6%) patients of this cohort died. Surgical and Autosplenectomy were seen in 18 (34.6%). These findings were similar to other SCD genotypes in this community. 19 (57.6%) were taking Hydroxyurea (HU) amongst the 33 patients who were prescribed HU. Haematological parameters showed a median (IQR) Hb (g/dl), MCV (fl), Retic count (%), WBC count(×109/L) and Platelet count(×109/L) of 9.7 (8.5-11.3), 74.9 (68.4-79.8), 4 (3.2-5.7), 9.9 (8.1-12.6) and 309 (239-428) respectively. The haemoglobin electrophoresis showed an elevated HbF, whereas serum bilirubin and LDH were elevated amongst the biochemical parameters. The use of hydroxyurea showed no impact on VOC, ACS, AVN, Stroke or mortality. SD Punjab is the third most common SCD genotype in Oman and was associated with recurrent VOC, ACS, AVN, and gall stones comparable to other SCD genotypes. Patients with > 3 VOC/year had significantly increased incidence of Stroke, AVN, and gallstones. However, HU was not associated with improved prognosis and better survival in this cohort of patients.

Hemoglobin scavenger receptor CD163 as a potential biomarker of hemolysis-induced hepatobiliary injury in sickle cell disease.

Sickle cell disease (SCD)-associated chronic hemolysis promotes oxidative stress, inflammation, and thrombosis leading to organ damage, including liver damage. Hemoglobin scavenger receptor CD163 plays a protective role in SCD by scavenging both hemoglobin-haptoglobin complexes and cell-free hemoglobin. A limited number of studies in the past have shown a positive correlation of CD163 expression with poor disease outcomes in patients with SCD. However, the role and regulation of CD163 in SCD-related hepatobiliary injury have not been fully elucidated yet. Here we show that chronic liver injury in SCD patients is associated with elevated levels of hepatic membrane-bound CD163. Hemolysis and increase in hepatic heme, hemoglobin, and iron levels elevate CD163 expression in the SCD mouse liver. Mechanistically we show that heme oxygenase-1 (HO-1) positively regulates membrane-bound CD163 expression independent of nuclear factor erythroid 2-related factor 2 (NRF2) signaling in SCD liver. We further demonstrate that the interaction between CD163 and HO-1 is not dependent on CD163-hemoglobin binding. These findings indicate that CD163 is a potential biomarker of SCD-associated hepatobiliary injury. Understanding the role of HO-1 in membrane-bound CD163 regulation may help identify novel therapeutic targets for hemolysis-induced chronic liver injury.

Assessment of visual and blood-related parameters among children with sickle cell anaemia at Murtala Muhammad Specialist Hospital in Kano, Nigeria.

Sickle cell disease (SCD) is a prevalent genetic disease worldwide and particularly in Nigeria. Retinopathy is a known complication of SCD, underscoring the need to assess visual parameters in children. This study aimed to evaluate the visual acuity (VA), color vision (CV), packed cell volume (PCV), and erythrocyte sedimentation rate (ESR) of Sickle cell anemic (SCA) patients attending the Sickle cell counseling unit of Murtala Muhammad Specialist Hospital (MMSH) in Kano. It was a descriptive cross-sectional study consisting of 60 participants, including 30 SCA patients and 30 healthy controls without systemic or ocular diseases, aged between 8 and 14 years. Visual acuity, CV, PCV, and ESR were assessed using Snellen Chart, Ishihara chart, Hematocrit test, and Westergren Method respectively. Data were analyzed using SPSS version 22.0. Statistical significance was set at P &lt; 0.05. Both SCA patients and controls demonstrated limited knowledge about VA, CV, and ESR tests, and a significant percentage had never undergone these tests. SCA patients exhibited mild to moderate visual impairment (VI) in both eyes, while controls had no VI. Abnormally low PCV and ESR values were observed in all SCA patients, whereas controls had normal values. Gender differences were observed in ESR levels, with females showing higher levels. Significant differences were found between controls and SCA patients in terms of VA, ESR, and PCV values. There was a general lack of awareness regarding the importance of VA and CV tests in the community. Visual impairment and abnormal PCV and ESR values were exclusive to the SCA patients, indicating their association with the disease.

Pulmonary Hypertension in Sickle Cell Disease: Novel Findings of Gene Polymorphisms Related to Pathophysiology.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD), affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of this disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is currently focused on the potential role of genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the transforming growth factor-beta (TGF-β) pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future, as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield reliable results that will allow a better understanding of SCD-related PH as a part of the disease's clinical spectrum. This review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

A novel high-titer, bifunctional lentiviral vector for autologous hematopoietic stem cell gene therapy of sickle cell disease

A major limitation of gene therapy for sickle cell disease (SCD) is the availability and access to a potentially curative one-time treatment, due to high treatment costs. We have developed a high-titer bifunctional lentiviral vector (LVV) in a vector backbone that has reduced size, high vector yields, and efficient gene transfer to human CD34+ hematopoietic stem and progenitor cells (HSPC). This LVV contains locus control region cores expressing an anti-sickling βAS3-globin gene and two microRNA adapted short hairpin RNA simultaneously targeting BCL11A and ZNF410 transcripts to maximally induce fetal hemoglobin (HbF) expression. This LVV induces high levels of anti-sickling hemoglobins (HbAAS3 + HbF), while concurrently reducing sickle hemoglobin (HbS). The reduction in HbS and increased anti-sickling hemoglobin impedes deoxygenated HbS polymerization and red blood cell sickling at low vector copy per cell in transduced SCD patient CD34+ cells differentiated into erythrocytes. The dual alterations in red cell hemoglobins ameliorated the SCD phenotype in the SCD Berkeley mouse model in vivo. With high titer and enhanced transduction of HSPC at low multiplicity of infection, this LVV will increase the number of patient doses of vector from production lots to reduce costs and help improve accessibility to gene therapy for SCD.

Osteonecrosis of the femoral and Humoral heads in sickle disease patients: Risk factor, Comorbiditis

ObjectivesAVN is the most common in Sickle Cell Disease patients, as SCD is common in the Jazan region of Saudi Arabia. The risk factors, and comorbidity regarding AVN of hip and shoulder joints in SCD patients were investigated in this study. MethodsThis retrospective cohort study was conducted at the two biggest hospitals in the Jazan region. A valid data collection sheet was used to collect information of SCD patients admitted to the wards or during follow-up. Staging for HAVN and SAVN was based on FICAT classification guidelines. Descriptive statistics and multivariate logistic regression were utilized. Resultstotal number of participants is 257, and 99 (38.5%) were under 14 years of age. About half of the participants are (134) females. Regarding participants' hemoglobin type, 78.6% had SCD, while 21.4% had sickle thalassemia. The occurrence of HAVN and SAVN is 14.8% and 5.4%, respectively. Of the 38 HAVN participants, 26.3% had comorbidities, and 5.3% had hypertension. The SAVN participants didn't report diabetes or hypertension. The vascular occlusive crisis is the most significant complication associated with SCD. Multivariate logistic regression determined some risk factors for SAVN and HAVN. ConclusionAVN is a frequent consequence of SCD, where the incidence rises with age. The vascular necrosis is the most significant complications. Continuing research on the prevention and non-surgical treatments of AVN caused by SCD must remain a top focus.

Platelet indices and neutrophil:lymphocyte ratio as a predictive tool in acute sickle cell vaso-occlusive crisis: A study protocol

Platelet indices and the neutrophil:lymphocyte ratio are newly emerging indicators of systemic inflammation in chronic diseases, such as hemoglobinopathies. The objectives of this study include estimation of platelet indices and neutrophil:lymphocyte ratio in sickle cell disease (SCD) patients with and without vaso-occlusive crisis. This cross-sectional study will be conducted in the Department of Medicine at a tertiary care teaching hospital situated in the rural area of Wardha district. The participants will include patients of SCD older than 18 years of age attending the sickle cell clinic. We hypothesize the use of neutrophil:lymphocyte ratio (NLR) and platelet indices as clinically significant predictive markers in acute sickle cell vaso-occlusive crisis.

Unraveling DEHP influence on hemoglobin S polymerization in sickle cell disease: Ex vivo, in vitro and in silico analysis

Sickle cell disease (SCD) is a hereditary hemoglobinopathy, caused by a mutation at position 6 of the β-globin chain and patients are frequently exposed to several blood transfusions in order to maintain physiological function. Transfusion blood bags are composed of PVC and phthalates (as DEHP) are often introduced to the material in order to confer malleability. In this sense, DEHP can easily elute to the blood and cause harmful effects. This study aimed to unravel DEHP effect on SCD patient's hemoglobin function. We found that HbS polymerization using whole erythrocytes is decreased by DEHP in ex vivo experiments and this effect might be mediated by the DEHP-VAL6 interaction, evaluated in silico. Isolated HbS exhibited less polymerization at low DEHP concentrations and increased polymerization rate at higher concentration. When analyzing the propensity to aggregate, HbS is more inclined to aggregate when compared to HbA due to the residue 6 mutation. Circular dichroism showed characteristic hemoglobin peaks for oxygenated HbS that are lost when oxygen is sequestered, and DEHP at higher concentration mildly recovers a peak close to the second hemoglobin one. Finally, by transmission electron microscopy we demonstrated that high DEHP concentration increased polymer formation with a more organized structure. These findings show for the first-time the beneficial effect of low-dose DEHP on HbS polymerization.

Beyond pulmonary embolism: Alternative diagnosis and incidental findings on CT pulmonary angiography in sickle cell disease.

Sickle cell disease (SCD) is a genetic hematological disorder associated with severe complications, such as vaso-occlusive crises, acute chest syndrome (ACS), and an increased risk of thromboembolic events, including pulmonary embolism (PE). The diagnosis of PE in SCD patients presents challenges due to the overlapping symptoms with other pulmonary conditions. Our previous study revealed that nearly 96% of computed tomography pulmonary angiography (CTPA) scans in SCD patients were negative for PE, highlighting a gap in understanding the significance of CTPA findings when PE is absent. In this retrospective follow-up study conducted at the Salmaniya Medical Complex in Bahrain, we examined SCD patients with HbSS genotypes who underwent CTPA from January 1, 2018, to December 31, 2021, for suspected PE, but the results were negative. The aim of this study was to identify alternative diagnoses and incidental findings from CTPA scans. Experienced radiologists reviewed the CTPA images and reports to assess potential alternative diagnoses and incidental findings, incorporating an additional analysis of chest X-rays to evaluate the diagnostic value of CTPA. Incidental findings were classified based on their location and clinical significance. Among the 230 evaluated SCD patients (average age 39.7 years; 53% male) who were CTPA negative for PE, 142 (61.7%) had identifiable alternative diagnoses, primarily pneumonia (49.1%). Notably, 88.0% of these alternative diagnoses had been previously suggested by chest radiographs. Furthermore, incidental findings were noted in 164 (71.3%) patients, with 11.0% deemed clinically significant, necessitating immediate action, and 87.8% considered potentially significant, requiring further assessment. Notable incidental findings included thoracic abnormalities such as cardiomegaly (12.2%) and an enlarged pulmonary artery (11.3%), as well as upper abdominal pathologies such as hepatomegaly (19.6%), splenomegaly (20.9%), and gallstones (10.4%). This study underscores the limited additional diagnostic yield of CTPA for identifying alternative diagnoses to PE in SCD patients, with the majority of diagnoses, such as pneumonia, already suggested by chest radiographs. The frequent incidental findings, most of which necessitate further evaluation, highlight the need for a cautious and tailored approach to using CTPA in the SCD population.

Electrocardiographic Abnormalities in Adult Homozygous Sickle Cell Disease Patients in Nnamdi Azikiwe University Teaching Hospital, Nnewi, South-Eastern Nigeria

Background; Sickle cell anaemia is the most common monogenic hematologic disorder in Nigeria. Cardiovascular pathology, resulting in electrocardiographic abnormalities are a common finding in adult sickle cell patients.&#x0D; Objective; This study investigated the pattern of electrocardiographic (ECG) abnormalities in steady state adult sickle cell anaemia (HbSS) patients and compared the findings with that of age and sex matched Haemoglobin AA(HbAA) controls.&#x0D; Methodology; Fifty steady state adult HbSS participants were recruited from the haematology clinic at Nnamdi Azikiwe University Teaching Hospital while fifty age and sex matched HbAA controls were recruited from the hospital community. Participants underwent resting 12 lead ECG using a Schiller CARDIOVIT AT-1 ECG machine. Data was analyzed using Statistical Package for Social Sciences version 21.&#x0D; Results; The prevalence of ECG abnormalities amongst the adult sickle cell participants and controls was 70% and 10% respectively. ECG abnormalities were more common amongst male sickle cell participants and left ventricle hypertrophy was the most frequent ECG abnormality detected.&#x0D; Conclusion; There is a high prevalence of ECG abnormalities amongst adult sickle cell anaemia patients. Regular Electrocardiography is recommended for early detection of these abnormalities for early treatment and improved quality of life.&#x0D; Keywords: Electrocardiographic Abnormalities, Sickle Cell Disease Patients, Nnamdi Azikiwe University, Haemoglobin AA

Emergency Department Utilization by Pediatric Patients With Sickle Cell Disease in Basrah, Iraq.

Background Patients with sickle cell disease (SCD) often present in the Emergency Department (ED) with acute and debilitating pain and other SCD-related complications. Objectives The objective is to analyze the causes of ED visits of pediatric patients with SCD, assess the burden of ED admission due to SCD in relation to other pediatric diseases, the treatment given, and the outcomes. Methods A prospective analytical study was conducted on children and adolescents with SCD, 1-14 years old who had been admitted to the ED at Basrah Maternity and Children Hospital over a six-month period. Patient's sociodemographic and clinical data, drug history, length of ED stay, complications, outcome, and readmissions were recorded. Results A total of 422 patients with SCD were admitted to ED during the study period representing 4.10% of the total admitted cases; 276(65.40%) of them were recruited in this study, and their mean age was 7.84 ±3.47 years. The main cause for ED admission was pain (73.91%), followed by infection (10.14%) and hemolytic crisis (6.15%). The mean duration of stay at ED was 6.11±1.87 hours. All admitted SCD patients had received analgesia; non-steroidal anti-inflammatory drugs (NSAIDs) were the commonest (80.4%), followed by acetaminophen (39.5%), and opioid narcotic (18.5%). Readmission within 30-days was reported in 82(29.71%) patients and was associated with the number of ED visits/last year (B=0.151, P=0.023), length of stay at ED (B=0.140, P=0.034) and severe disease (B=0.253, P<0.001). Conclusions Acute painful episodes were the main cause of ED admission. Although most patients with pain did receive NSAIDs, only a small percentage of them did receive opioids. About one-third of patients have been readmitted within 30 days, and readmission was associated with the number of ED visits/last year, disease severity, and length of ED stay. These findings can help in establishing local guidelines for managing such patients in the ED especially pain management.

Multi-center study on mortality in children, and adults with sickle cell anemia-risk factors and causes of death

Sickle cell disease (SCD) is a major public health burden worldwide with increasing morbidity and mortality. The study evaluates the risk factors associated with mortality in SCD patients, between the years 2006 and 2020 at three hospitals in Oman. The analysis includes clinical manifestations, haematological, biochemical, and radiological parameters, use of antibiotics, and blood and exchange transfusions. Our cohort included 123 patients (82 males, 41 females), with a median age of 27 (Interquartile Range 21–35 years). SCD related complications included acute chest syndrome (ACS) in 52.8%, splenic sequestration in 21.1%, right upper quadrant syndrome in 19.5%, more than > 6 VOC/year in 17.9%, and stroke in 13.8%. At the terminal admission, patients had cough, reduced O2 saturation, crepitation and fever in 24.4%, 49.6%, 53.6% and 68.3% respectively. Abnormal chest X-ray and chest CT scan were seen in 57.7%, and 76.4% respectively. Laboratory parameters showed a significant drop in hemoglobin (Hb) and platelet counts from baseline, with a significant rise in WBC, LDH and CRP from baseline (p < 0.05, Wilcoxon Signed Ranks test). All patients received antibiotics, whereas, 95.9% and 93.5% received simple blood transfusions, and exchange transfusions respectively, and 66.6% required non-invasive ventilation. Among the causes of death, ACS is seen in 32 (26%), sepsis in 49 (40%), and miscellaneous in 42 (34%). Sudden death was seen in 32 (26%) of patients. Male gender, with low HbF, rapid drop in Hb and platelet, and increased in WBC, LDH, ferritin, and CRP, correlated significantly with mortality in this cohort.

Long-Term Ovarian Function Assessment After Haematopoietic Stem Cell Transplantation in Female Sickle Cell Anaemia Survivors.

Haematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for sickle cell anaemia (SCA). While HSCT offers the possibility of disease remission, it can also lead to long-term complications, including gonadal dysfunction and premature menopause. We conducted a retrospective cohort study of female survivors who had hydroxyurea therapy and those who underwent post-HSCT follow-up for SCA at a teaching hospital in Lagos, Nigeria, between January 2019 and December 2022. Participants were eligible if they were at least five years post-HSCT or hydroxyurea treatment and had available serum samples for markers of ovarian function measurement. Demographic and clinical data were collected from the hospital register and patients' medical records. Serum levels of oestradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH) were measured using the Abbott Architect i1000SR chemiluminescent immunoassay analyzer (Abbott Diagnostics, Abbott Park, IL). Descriptive statistics and inferential analyses were used to assess the relationship between markers of ovarian function (FSH and AMH) and clinical parameters. There were statistically significant differences in the median serum levels of all the assessed endocrine hormones between the HSCT and non-HSCT (hydroxyurea) groups of SCA survivors. Up to 82.6% of the SCA survivors experienced ovarian dysfunction after HSCT treatment. Impaired ovarian function in SCA survivors was associated with a longer median follow-up duration than in SCA survivors who had normal ovarian function (12.0 vs. 7.5 years, p = 0.048). There were higher odds of impaired ovarian function in the SCA survivors who had myeloablative regimens than in those who had reduced intensity conditioning regimens (94.1% vs. 50.0%, p = 0.040). Our study highlights the significant impact of HSCT on long-term ovarian function in female SCA survivors. However, further prospective studies with larger sample sizes and longer follow-up periods are required to confirm our findings and elucidate the factors influencing ovarian function in SCA survivors of HSCT. In addition, studies are also needed to further elucidate the optimal transplant protocols and fertility preservation strategies to minimize gonadal toxicity and preserve reproductive potential in female SCA patients undergoing HSCT.

Good engraftment after reduced intensity targeted busulfan-based conditioning and matched related donor hematopoietic cell transplantation in hemoglobinopathies.

Hematopoietic cell transplantation (HCT) is an established curative therapy for transfusion-dependent thalassemia (TDT) and sickle cell disease (SCD). The latest American Society of Hematology guidelines recommend myeloablative preparative regimen in patients under 18years of age. The objective was to demonstrate safety and efficacy of a reduced intensity conditioning (RIC) regimen including high-dose fludarabine, anti-thymocyte globulin, and targeted busulfan as a single alkylator to sub-myeloablative exposures. Between 2012 and 2021, 11 patients with SCD and five patients with TDT and matched related donor (MRD) HCT were included. The median age at transplantation was 8.3years (range: 3.7-18.8years). The median administered busulfan AUC was 67.4mg/L×h (range: 60.7-80mg/L×h). Overall survival was 93.8% and event-free survival 87.5% with one engrafted SCD patient with pre-existing moyamoya disease succumbing after drainage of a subdural hematoma. One SCD patient developed a secondary graft failure and was treated with a second HCT. Myeloid chimerism was full in all other patients with a median follow-up time of 4.1years (range: 2.0-11.1years), whereas T-cell donor chimerism was frequently mixed. This RIC conditioning followed by MRD HCT is sufficiently myeloablative to cure pediatric patients with hemoglobinopathies without the need for additional total body irradiation or thiotepa.