Hereditary Hemoglobinopathies Research Articles

Malnutrition in sickle cell anemia: Prevalence, impact, and interventions: A Review.

Sickle Cell Anemia (SCA) is a hereditary hemoglobinopathy characterized by chronic hemolytic anemia, vaso-occlusive events, and a wide range of clinical complications. Malnutrition, often an underexplored aspect of this complex condition, plays a critical role in disease management and overall patient well-being. This publication provides a comprehensive review of the prevalence, impact, and interventions related to malnutrition in individuals with SCA. A thorough literature review reveals the multifaceted challenges faced by SCA patients in maintaining adequate nutrition. The pathophysiology of SCA, involving chronic inflammation, oxidative stress, and hypermetabolism, contributes to increased nutritional requirements and altered dietary patterns. Factors such as reduced appetite, nutrient malabsorption, dietary restrictions, and socioeconomic disparities further exacerbate the risk of malnutrition. Malnutrition is a prevalent issue among individuals with SCA, affecting patients of different age groups and disease severities. Nutritional deficiencies, including vitamins, minerals, and essential nutrients, are common in this population. The impact of malnutrition on disease outcomes is significant, with associations between nutrient status and complications such as pain crises, infections, and impaired quality of life. This paper also reviews nutritional interventions aimed at addressing malnutrition in SCA patients. While dietary counseling, supplementation, and personalized nutrition plans have shown promise in improving nutritional status, challenges such as patient adherence and access to healthcare must be addressed to optimize their effectiveness.

Revolutionary breakthrough: FDA approves CASGEVY™, the first CRISPR/Cas9 gene therapy for sickle cell disease

Revolutionary breakthrough: FDA approves CASGEVY™, the first CRISPR/Cas9 gene therapy for sickle cell disease

Managing gastrointestinal challenges: Diarrhea in sickle cell anemia.

Sickle cell anemia (SCA), a hereditary hemoglobinopathy, is characterized by the presence of abnormal hemoglobin and has long been associated with a wide range of complications. While much attention has been given to the condition hematological aspects, gastrointestinal complications, particularly diarrhea, have been relatively understudied and often overlooked. This publication delves into the management of gastrointestinal challenges, with a focus on diarrhea, in individuals living with SCA. The pathophysiology of SCA is intrinsically linked to gastrointestinal complications, and diarrhea is a common manifestation of this condition. This abstract publication outlines the key elements discussed in the full-length work, which includes the clinical presentation of diarrhea in these patients, the diagnostic tools used to evaluate the condition, and various management strategies to alleviate symptoms and enhance the overall quality of life for affected individuals. The paper emphasizes the importance of patient education, offering healthcare professionals valuable insights into how to inform and support patients in managing their conditions effectively. It also highlights the need for continued research to further our understanding of gastrointestinal challenges in SCA and to identify potential areas for future therapeutic interventions. Ultimately, the comprehensive management of diarrhea in individuals with SCA is vital for their overall well-being. This publication serves as a valuable resource for healthcare providers, researchers, and caregivers in addressing the gastrointestinal challenges that accompany SCA, ultimately working toward a better quality of life for those affected by this condition.

Biased agonism of protease-activated receptor-1 regulates thromboinflammation in murine sickle cell disease

AbstractSickle cell disease (SCD) is a hereditary hemoglobinopathy marked by hemolytic anemia and vaso-occlusive events (VOEs). Chronic endothelial activation, inflammation, and coagulation activation contribute to vascular congestion, VOEs, and end-organ damage. Coagulation proteases such as thrombin and activated protein C (APC) modulate inflammation and endothelial dysfunction by activating protease-activated receptor 1 (PAR1), a G-protein–coupled receptor. Thrombin cleaves PAR1 at Arg41, while APC cleaves PAR1 at Arg46, initiating either proinflammatory or cytoprotective signaling, respectively, a signaling conundrum known as biased agonism. Our prior research established the role of thrombin and PAR1 in vascular stasis in an SCD mouse model. However, the role of APC and APC-biased PAR1 signaling in thrombin generation, inflammation, and endothelial activation in SCD remains unexplored. Inhibition of APC in SCD mice increased thrombin generation, inflammation, and endothelial activation during both steady state and tumor necrosis factor α challenge. To dissect the individual contributions of thrombin-PAR1 and APC-PAR1 signaling, we used transgenic mice with point mutations at 2 PAR1 cleavage sites, ArgR41Gln (R41Q) imparting insensitivity to thrombin and Arg46Gln (R46Q) imparting insensitivity to APC. Sickle bone marrow chimeras expressing PAR1-R41Q exhibited reduced thrombo-inflammatory responses compared with wild type PAR1 or PAR1-R46Q mice. These findings highlight the potential benefit of reducing thrombin-dependent PAR1 activation while preserving APC-PAR1 signaling in SCD thromboinflammation. These results also suggest that pharmacological strategies promoting biased PAR1 signaling could effectively mitigate vascular complications associated with SCD.

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.

Spinal Manifestation of Sickle Cell Disease. A Report On 35 Patients with Literature Review

Background: Sickle cell disease is a hereditary hemoglobinopathy affecting the spine in a wide range of pathology. Despite the several pathological involvements, some patients remain asymptomatic even with positive imaging findings. Objectives: Theme of this study is to report the various pathological disorders involving the spine of patients with sickle cell disease in Basra “south of Iraq” Patients and method: 35 Homozygous and heterozygous sickle cell patients were included in this study. 22 Males and 13 females, their age range from 6 to 69 years they were evaluated clinically, and also by laboratory imaging studies like plain radiography, computerized tomography, magnetic resonance imaging and mineral bone density “DEXA scan “ Results: 54% of the patients were homozygous, and the remaining were heterozygous, 66% of them were asymptomatic, back pain was the complaint in 60% while spine tenderness was reported in 40%, 31% had tenderness in the sacroiliac region and only 6% had neurological claudication and focal neurological deficit. Biconcave vertebra was confirmed in 72% of the patients and mainly localized in the lumbar Spine, MRI findings of vertebral infarction were observed in 58% of the studied patients while sacroiliac joint changes appeared in 60%, 60% of those who had DEXA scan showed low mineral bone density in the lumbar spine Conclusion: Sickle cell disease involve the whole Spine in a wide range of pathological process, some show clinical symptoms, and some remain asymptomatic in spite of changes. The structural changes are more obvious in the homozygous group (55) the lumber spine is dominantly involved, disc prolapse, and neurological deficit is rare while the low mineral changes is common. We did not report a case of spondylodiscitis in this series, though it is very much expected, so routine screening of the spine in sticklers is mandatory

Is There any Relationship Between the Repeated Complications of Sickle Cell Disease and the Potential Development of Acute Leukemia?

Sickle cell disease (SCD) is a severe monogenic hereditary hemoglobinopathy that is characterized by repeated clinical and biological manifestations able to generate stress erythopoiesis. A clonal hematopoiesis involving mainly variants of TP53, DNMT3A, ASXL1, and/or TET2 may be more prevalent in patients with SCD, suggesting that mutations in these genes may lead to an increased risk of leukemia. An increased prevalence of leukemia in patients with SCD has been confirmed by an increasing number of acute myeloid leukemia cases with myelodysplastic features reported in this patient population even in the absence of disease-modifying treatments. This leads to the hypothesis of a mechanism involving multifactorial causes through the pathophysiologic manifestations of SCD, in which cells are undergoing constant hematopoietic hyperplasia, inducing genomic damage and somatic mutations.

Angioid Streaks Remain a Challenge in Diagnosis, Management, and Treatment.

Aim: Angioid streaks (ASs) are a rare retinal condition and compromise visual acuity when complicated with choroidal neovascularization (CNV). They represent crack-like dehiscences at the level of the Bruch's membrane. This objective narrative review aims to provide an overview of pathophysiology, current treatment modalities, and future perspectives on this condition. Materials and Methods: A literature search was performed using "PubMed", "Web of Science", "Scopus", "ScienceDirect", "Google Scholar", "medRxiv", and "bioRxiv." Results: ASs may be idiopathic, but they are also associated with systemic conditions, such as pseudoxanthoma elasticum, hereditary hemoglobinopathies, or Paget's disease. Currently, the main treatment is the use of anti-vascular endothelial growth factors (anti-VEGF) to treat secondary CNV, which is the major complication observed in this condition. If CNV is detected and treated promptly, patients with ASs have a good chance of maintaining functional vision. Other treatment modalities have been tried but have shown limited benefit and, therefore, have not managed to be more widely accepted. Conclusion: In summary, although there is no definitive cure yet, the use of anti-VEGF treatment for secondary CNV has provided the opportunity to maintain functional vision in individuals with AS, provided that CNV is detected and treated early.

Prospective observational study iron deficiency anemia clinical profile in children with sickle cell disease: a study protocol

Background Sickle cell disease, a hereditary hemoglobinopathy, presents complex clinical challenges including increased susceptibility to iron deficiency anemia (IDA). However, the clinical profile of IDA in pediatric patients with sickle cell disease still needs to be adequately characterized. This study aims to comprehensively investigate the prevalence, severity, associated risk factors, and potential impact of IDA on morbidity and mortality in this vulnerable population. Methods A prospective observational study will be conducted on 303 children from January 2024 to December 2024 at the Department of Pediatrics, Jawaharlal Nehru Medical College and AVBR Hospital, Sawangi, Wardha. Participants will include pediatric patients diagnosed with sickle cell disease, with informed consent from their parents or legal guardians. Data will be collected through clinical assessments, blood sample analyses for hematological parameters, and systematic recording of relevant clinical information. Statistical analyses, including Fisher’s exact test, Chi-square test, and Student’s t-test, will be used to assess the data, with a significance level set at p < 0.05. Expected outcomes This study aims to provide critical insights into the prevalence and clinical profile of IDA in children with sickle cell disease, shedding light on potential risk factors and correlations with comorbid conditions. Furthermore, it seeks to explore the relationship between IDA and disease-related morbidity and mortality.

Death due to sickle cell crisis: a case report.

Sickle cell disease (SCD) is the most common hereditary hemoglobinopathy worldwide. It results in characteristic acute and chronic findings on postmortem computed tomography (PMCT), macroscopic and microscopic examinations. While the diagnostic imaging and macroscopic features are not specific for SCD on their own, when coupled with microscopic features such as sickled erythrocytes and evidence of chronic venous congestion (i.e., Gamna-Gandy bodies), these clues can help alert forensic pathologists to the presence of SCD. Despite the prevalence of the disease and the constellation of findings alluded to above, SCD is not often explored in forensic pathology literature. This case demonstrates classic acute and chronic features of SCD on PMCT, macroscopic and microscopic examinations. It explores the pathophysiology leading to sudden and unexpected death in a person with SCD and possible pitfalls in attribution of cause of death.

Minor physical anomalies including palatal rugae pattern and palatal dimensions in children with sickle cell disease: A cross-sectional analytical study

BackgroundSickle cell disease (SCD) is the most common hereditary hemoglobinopathy, which delays growth leading to an altered skeleton and craniofacial pattern. Palatal rugae patterning has been considered the regulator of the development of the palate. The purpose of the research work was to study the morphology of the palate, rugae pattern, and its dimensions in SCD children and compare them with healthy normal children, and to evaluate its role as minor physical anomalies (MPAs). MethodsA cross-sectional case-control study was designed as per STROBE guidelines. The sample comprised 50 children diagnosed with sickle cell disease (Group SCD) and 50 normal healthy children as control (Group C) belonging to the same age group (10–18 years). Dental impressions were made, followed by the pouring of dental casts. The length of the palatal rugae was measured and categorized into primary (>5 mm), secondary (3 mm–5 mm), and fragmentary rugae (<3 mm). The shape of each primary palatal rugae was identified and categorized as curved, wavy, straight, circular and non-specific. Linear and angular measurements of the palatal rugae patterns and palatal dimensions (width, height, area) were measured and recorded. ResultsThe total number of palatal rugae and fragmentary rugae was lesser in Group SCD than in Group C (p < 0.05). The depth of the palate was significantly increased, whereas the area of the palate significantly decreased in Group SCD. ConclusionsThe children with SCD showed distinctive palatal rugae patterns and dimensions when compared with normal healthy children that can be attributed as potential MPAs for sickle cell disease. Children with SCD had an under-developed palatal rugae pattern with a deep, narrow and small palate when compared to healthy children.The dimensions of the palatal rugae pattern in SCD showed reduced distance between the incisive papilla and the first and last rugae, indicating a further decrease in the anteroposterior dimensions of the palate. These findings may aid in the early diagnosis and prevention of malocclusion in children with SCD by appropriate interceptive orthodontic treatment

Clinical Implications of Neutrophil-to-Lymphocyte Ratio in Sickle Cell Disease

Sickle Cell Disease (SCD) is a hereditary hemoglobinopathy characterized by chronic hemolytic anemia and vaso-occlusive events. In recent years, the Neutrophil-to-Lymphocyte Ratio (NLR) has emerged as a potential biomarker with prognostic and diagnostic significance in various medical conditions. This review explores the clinical implications of NLR in the context of SCD, shedding light on its role as a valuable indicator of inflammation, disease severity, and treatment response. The inflammatory state is a key contributor to the pathophysiology of SCD, influencing disease progression and complications. NLR, calculated from routine complete blood counts, reflects the balance between the immune response’s cellular components and has been implicated in assessing the inflammatory status in various diseases. In the context of SCD, elevated NLR has been associated with increased vaso-occlusive events, suggesting its potential utility as a predictive marker for disease complications. In conclusion, this perspective review consolidates current knowledge on the clinical implications of NLR in Sickle Cell Disease. It highlights the potential of NLR as a readily available and cost-effective biomarker for assessing inflammation, predicting disease severity, and monitoring treatment response in individuals with SCD. As the understanding of the immunological aspects of SCD continues to evolve, NLR stands out as a promising parameter that may contribute to a more comprehensive approach to managing this complex hematologic disorder.

Oxidative Stress and Redox Signaling in the Pathophysiology of Sickle Cell Disease: A Review

Sickle Cell Disease (SCD) is a hereditary hemoglobinopathy characterized by the aberrant hemoglobin S, resulting in the formation of sickle-shaped red blood cells and a cascade of clinical complications. While the molecular aspects of SCD are well-elucidated, recent investigations underscore the critical influence of oxidative stress and redox signaling in the disease’s pathophysiology. This comprehensive review synthesizes current knowledge on the interplay between oxidative stress, redox signaling, and SCD, providing insights into potential therapeutic targets. Discussions encompass the generation of reactive oxygen species (ROS), antioxidant defense mechanisms, and the activation of redox-sensitive signaling pathways. The consequences of oxidative stress, such as vaso-occlusion, inflammation, and endothelial dysfunction, are examined in detail. Furthermore, the review evaluates existing antioxidant therapies, explores potential strategies targeting redox signaling pathways, and discusses emerging therapeutic targets. By elucidating the intricate relationship between oxidative stress and SCD, this review aims to advance our understanding of the disease’s complexity and pave the way for innovative therapeutic interventions, offering renewed hope for enhanced patient care and management.

Cardiovascular complications of sickle cell disease: A primer for the general clinician

Sickle cell disease (SCD) is the most common hereditary hemoglobinopathy and mainly affects individuals of African ancestry. As survival has improved especially in high-income countries, increased rates of cardiopulmonary complications such as pulmonary hypertension, heart failure with diastolic dysfunction, and sudden death are encountered in clinical practice. These complications are the leading causes of morbidity and mortality as these individuals survive into adulthood. Understanding the need for, early identification, timely intervention, and implementation of preventive strategies are critical in reversing this trend and improving quality of life and survival rates. This manuscript aims to provide a comprehensive review of the pathogenesis of cardiovascular complications associated with sickle cell disease and equip the clinician with tools to facilitate the early diagnosis and management of patients with SCD as increasing numbers survive into adulthood.

Myeloid Neoplasia in Patients with Hereditary Hemoglobinopathies and Hemolytic Anemias (HHAs)

Background: Studies have shown an increased incidence of myeloid neoplasia (MN) in patients with sickle cell disease (SCD). It is hypothesized that increased erythropoietic stress may influence acquisition of molecular drivers of MN in SCD. However, present understanding of MN presentation and outcomes in SCD and other hereditary hemoglobinopathies and hemolytic anemias (HHAs) is limited to case reports. Systematic evaluation of MNs in patients with HHAs will better contextualize the risk of MN in this population relative to non-HHA controls. Methods: Patients with HHAs were identified from the Mass General Brigham Research Patient Data Repository using ICD-10 codes. Evaluated HHAs included sickle cell disease (SCD), sickle cell trait (SCT), thalassemia major, thalassemia trait, other hemoglobinopathy traits, and hereditary spherocytosis or elliptocytosis. A final HHA-MN cohort included patients with laboratory confirmed HHA diagnoses as well as incident myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), Ph+ chronic myelogenous leukemia (Ph+ CML), Ph negative myeloproliferative neoplasms (Ph- MPNs) or acute myeloid leukemia (AML). A control cohort of non-HHA MN patients was obtained from the Dana-Farber Hematologic Malignancies Data Repository. Clinical, molecular, and survival data were summarized and compared between HHA-MN and controls. Results: The HHA-MN cohort included 62 patients with HHAs and incident MN (Table 1). HHAs included SCD (n = 6, 9.7%), SCT (n = 9, 14.5%), thalassemia trait (n = 36, 58.1%), thalassemia major (n = 2, 3.2%), hereditary spherocytosis or elliptocytosis (n = 4, 6.5%), and other hemoglobinopathy traits (n = 5, 8.1%). MN was diagnosed at a median age of 61 years [IQR: 48, 70] in the HHA-MN cohort and incident MNs included AML (n = 12, 19.4%), MDS/CMML (n = 22, 35.4%), Ph+ CML (n = 6, 9.7%), and Ph- MPNs (n = 22, 35.4%). A control population of 3388 MN patients without HHA included cases of AML (n = 754, 22.2%), MDS/CMML (n= 1272, 37.5%), Ph+ CML (n = 354, 10.4%), and Ph- MPNs (n = 1008, 29.7%). Compared to HHA patients, control patients were older at MN diagnosis (median age 65 years [IQR: 56, 73], p = 0.0071), driven by significantly younger ages at AML diagnosis for HHA-MN patients (median age 50 years [IQR: 33, 63] vs 65 years [IQR: 57, 73], p =0.0044). AML was the most common MN in SCD (n = 4, 66.7%) whereas incident MDS/CMML was the predominant MN among individuals with thalassemia trait (n = 12, 33.3%) or hereditary spherocytosis and elliptocytosis (n = 2, 50%). Diagnostic cytogenetic data were available for 45 patients in the HHA-MN cohort (72.6% of cohort). Complex karyotype, defined as 3 or more chromosomal aberrations, was observed in 3 of 11 (27.3%) AML, 3 of 19 (15.8%) MDS/CMML and 1 of 17 (5.9%) Ph- MPN cases. Of the 33 HHA-MN patients with available diagnostic next generation sequencing, 60.6% had 2 or more pathogenic mutations at MN diagnosis. Including 2 cases of TP53-mutant AML in patients with SCD, the majority (90%) of AML and 38.9% of MDS/CMML diagnosed in HHA-MN patients were intermediate to adverse risk by ELN criteria or intermediate to very high risk by IPSS-R, respectively. High risk disease was also common in our control MN cohort, where 88.3% of AML cases were intermediate or adverse risk by ELN criteria and 55.9% of MDS/CMML cases were intermediate to very high risk by IPSS-R. Survival varied by subtype of HHA and MN (Figure 1). Survival was lowest for SCD (33.3% at 60-months) and highest for thalassemia traits (67.1% at 60 months). In HHA patients compared to controls, 60-month survival was 65.0% overall (vs 56.4%), 14.3% for AML (vs 23.8%), 51.0% for MDS/CMML (vs 43.9%), 90.5% in Ph- MPN (vs 80.6%), and 100% in Ph+ CML (vs 89.4%). Within the limitations of our sample size, survival differences were not statistically significant. Conclusion: In this retrospective analysis, we observe younger age of diagnosis of myeloid malignancy for patients with HHAs compared to non-HHA controls. Inferior survival in SCD and thalassemia major is largely explained by a higher proportion of AML diagnoses in patients with SCD. AML and MDS/CMML diagnosed in HHA patients tended to be intermediate or high-risk disease, with survival similar to the non-HHA control population that was also enriched for higher risk patients. Validation of our findings in an expanded cohort of HHA patients is currently underway.

Mortality Trends and Causes of Death in Individuals with Thalassemia: A Population-Based Retrospective Study in the United States from 1999 to 2020

Background Thalassemia is a hereditary hemoglobinopathy that results in ineffective erythropoiesis. Patients with thalassemia have varying degrees of severity ranging from mild anemia to severe complications due to iron overload. Despite its clinical significance, the study on the mortality rate among patients with thalassemia in the United States (US) remains scarce. Objective This study aimed to analyze the trends in thalassemia-related mortality rate and the underlying causes of death among individuals with thalassemia. Methods We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database and performed serial cross-sectional analyses of national death certificate data for thalassemia-related mortality among patients of all ages. Thalassemia (International Classification of Diseases, Tenth Revision [ICD-10] D56) was listed as the contributing cause of death. We calculated age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and examined the trends over time by estimating the average annual percent change (AAPC) using the Joinpoint Regression Program. Subgroup analyses were performed by sex, age, race, census region, and urbanization level. Results From 1999 to 2020, there were 2,797 deaths related to thalassemia. Among these deaths, beta thalassemia accounted for 24.87%, alpha thalassemia accounted for 6.00%, thalassemia trait accounted for 2.52%, dominant thalassemia, hemoglobin C thalassemia, mixed thalassemia, or thalassemia with other hemoglobinopathies accounted for 1.92%, and unspecified thalassemia accounted for 64.37%. The baseline demographics of patients who met the inclusion criteria are shown in Table 1. Thalassemia-related mortality rate showed an overall decline in trend from 0.50 (95% CI, 0.41 - 0.58) per 1,000,000 individuals in 1999 to 0.34 (95% CI, 0.28 - 0.40) per 1,000,000 individuals in 2019, but increased to 0.48 (95% CI, 0.41 - 0.55) per 1,000,000 individuals in 2020 (Figure 1). The highest AAMR was observed among Asians (1.34 [95% CI, 1.20 - 1.47] per 1,000,000 individuals), followed by non-Hispanic Blacks (0.65 [95% CI, 0.59 - 0.71] per 1,000,000 individuals), non-Hispanic Whites (0.32 [95% CI, 0.30 - 0.33] per 1,000,000 individuals), and Hispanics (0.11 [95% CI, 0.08 - 0.14] per 1,000,000 individuals). The most common underlying causes of death among individuals with thalassemia were cardiovascular causes (26.0%), followed by hematological causes (20.7%), malignancy (17.8%), endocrine disorders (6.3%), respiratory causes (6.2%), disorders of the nervous system (5.0%), gastrointestinal diseases (4.9%), psychiatric disorders (3.3%), infection (3.0%), and other causes (6.7%). Among the cardiovascular causes, ischemic heart disease (11.0%) was the most common cause, followed by hypertensive disease (3.0%), cerebrovascular disease (1.7%), aortic valve disease (1.1%), cardiomyopathy (0.79%), and atrial fibrillation and flutter (0.79%). The urban population had a higher AAMR compared to the rural population (0.43 [95% CI, 0.41 - 0.45] per 1,000,000 individuals vs. 0.29 [95% CI, 0.26 - 0.32] per 1,000,000 individuals). Nevertheless, the rural areas exhibited an increasing trend in the AAMR (+6.90%) while the urban areas exhibited a decreasing trend in the AAMR (-11.36%) during the study period. Conclusion While there has been an overall decline in the thalassemia-related mortality rate, variations exist among different races, geographic regions, and urbanization levels. Our study emphasizes the need for targeted interventions to address these disparities.

Use of Race and Ethnicity in Sickle Cell Disease Research

Introduction Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by chronic hemolytic anemia, devastating ischemic pain crises and chronic organ damage, resulting in shortened lifespan. Ethnicity and race are often mentioned in SCD research. Possibly, since SCD is particularly prevalent amongst people who originate from sub-Saharan Africa. In research studies, ethno racial categories (ERCs) are frequently considered confounding variables. However, these ERCs are often large aggregate categories and include individuals with a diversity in phenotype, exposures and genetic make-up. Recent journal submission guidelines urge researchers, when applicable, to declare the relevance of the use of ERCs to the study as well as the modality through which an ERC is determined (e.g. self-identification, country of birth, visual identification by the observer). Providing such detailed information is important because true confounders with a specific feature might distort study results. However, when operationalizing ERCs in SCD research, there exists a risk of reification of already marginalized populations as both a social and a biological group. Therefore, contextualization is essential when deciding to use ERCs in SCD research. This study aims to provide an overview of how ethnicity and race are applied in SCD research. Methods We systematically searched the literature to explore the current practice of ERCs in SCD research across world regions. Embase and Medline were systematically searched in November 2022 for all published articles on SCD published from 2011 onwards. Studies were considered eligible when cases defined as individuals with SCD and controls individuals without SCD. A total of 1,105 articles in SCD research were included. Of these articles, 1,085 were domestic studies and 20 international studies. Statistical tests and models implemented in R included chi-square tests and univariate linear regression. Results In 27% (298/1,085) of all studies, ERC confounder adjustment occurred. This methodological practice was dependent on geographical region the research subjects were sourced from (p&amp;lt;0.05), as made visible in Figure 1. In 175/302 (57%) of studies with a North American study population ERC confounder adjustment took place, as well as in 45% [58/129]) of the studies reporting on a European study population. In contrast, in 6% (14/239) of sub-Saharan African study populations, ERC confounder adjustment was performed (Table 1). Of the twenty international studies, six operationalized ERCs as confounders. In five publications, the control group was sourced from the same country as the SCD cases. One study used a healthy Congolese reference population as a control cohort whilst the SCD patients were from France. ERC confounder adjustment also varied with the biomedical discipline in which the article was published. Compared to Hematological journals, articles published in journals with categories “Medicine, General &amp; Internal medicine” (OR=0.30, 95% CI -1.76 - -0.67, p&amp;lt;0.0001), were less likely to adjust for ERCs as confounders whereas articles in Ophthalmological journals (OR= 3.36, 95% CI 0.27 - 2.23, p=0.01) were more likely to do so. Of the studies that used ERC confounder adjustment, 80% (239/298) did not explain why this was relevant. Furthermore, in 70% (209/298) of these ERC-adjusted studies, it was unclear through which modality ERCs were determined. In the papers that described modalities, 49% (44/89) used ERCs from pre-existing databases, 18%(16/89) used sibling/relative recruitment, 30% (27/89) used self-reporting ERCs and 2% (2/89) used multiple ways to classify ethnicity or race. Moreover, in 28% (83/298) of the ERC-adjusted studies, it was not clear which specific categories were used. Conclusion ERC confounder adjustment is a common occurrence in SCD case-control studies in the United States and Europe. Furthermore, contrary to current author guideline recommendations, reporting on ethnicity and race in SCD studies is frequently inconsistent and incomplete. This confuses the possible relevance of ERCs to the study and inadvertently reinforces reification of these constructs. Moving forward, we recommend the promotion of global guidelines around the use of ERCs in case-control studies to stimulate further research into uncovering specific relevant mechanisms that create differences in health outcomes.

Relation between interferon-gamma gene expression and its serum level with thyroid hormone status and Ferritin level in Iraqi sickle cell anemia patients

The hereditary hemoglobinopathy known as sickle cell disease is characterized by abnormal hemoglobin synthesis, hemolytic anemia, and intermittent obstruction of tiny blood arteries. The current investigation aims to study the relationship between interferon-gamma gene expression and serum levels with thyroid hormone status and Ferritin levels in sickle cell anemia patients. Blood samples were collected from 50 patients suffering from SCA and 50 healthy volunteers as a control group. The results of the relation of IFN-γ serum level with T3, T4 and TSH levels showed a positive relationship between IFN-γ serum and TSH levels. At the same time, an inverse association to T3 and T4 levels with high significance also showed high IFN-γ gene expression (10.78 ±5.06 Fold) in the patient group as compared with control (2.079 ±0.52 Fold) at a significant difference, as well as the results found acquire strong positive association between IFN-γ serum level and IFN-γ mRNA expression in the patient group compared with the control group. The current study concluded that there was an inverse association among T3, T4 and IFN-γ serum with high significance, as high gene expression of IFN-γ, and a strong positive association between IFN-γ serum level and IFN-γ mRNA expression. Keywords: IFN-γ, SCA, Ferritin, TSH, T3, T4.

A Study on Knowledge, Attitudes, Practice and Awareness towards Pre-Marital Carrier Screening of Thalassemia among the University Students of Biological Faculty in Bangladesh: A Cross-Sectional Study

Thalassemia is a hereditary hemoglobinopathies that results from the absence of a globulin chain and it is a very common problem in Southeast Asia. Like many other countries’ community based premarital carrier screening (PMCS) of thalassemia is extremely rare in Bangladesh. This study aimed to investigate knowledge, attitude, practice, and awareness towards PMCS among University students in Bangladesh. A cross-sectional study was conducted from January to March 2020 using a self-administered questionnaire which was distributed to 911 Jahangirnagar University students aged 18 to 24. The questionnaire was composed of five parts: personal information, knowledge, attitudes, practice, and awareness. On the basis of the answers, knowledge, attitudes, practice, and awareness towards PMCS were evaluated. About (88.80%) of the total participating students thought that PMCS is necessary before marriage. In the case of thalassemia carrier parents, 81.00% of students replied that prenatal screening is important before pregnancy. 610 students (66.95%) of the total 911 students considered that thalassemia can be caused by marrying between blood relatives. Most of the students (79.80%) supported that thalassemia screening should be an obligatory procedure and 91.98% would like to raise social awareness about PMCS and thalassemia. The students of Jahangirnagar University have good knowledge about PMCS program and a positive attitude but it is difficult to implement in real life without continuing practice. The outcome of this study suggested the necessity of increasing student’s awareness of Bangladeshi PMCS program.

Hemolysis dictates monocyte differentiation via two distinct pathways in sickle cell disease vaso-occlusion.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by painful vaso-occlusive crises (VOC) and chronic hemolysis. The mononuclear phagocyte system is pivotal to SCD pathophysiology, but the mechanisms governing monocyte/macrophage differentiation remain unknown. This study examined the influence of hemolysis on circulating monocyte trajectories in SCD. We discovered that hemolysis stimulated CSF-1 production, partly by endothelial cells via Nrf2, promoting classical monocyte (CMo) differentiation into blood patrolling monocytes (PMo) in SCD mice. However, hemolysis also upregulated CCL-2 through IFN-I, inducing CMo transmigration and differentiation into tissue monocyte-derived macrophages. Blocking CMo transmigration by anti-P selectin antibody in SCD mice increased circulating PMo, corroborating that CMo-to-tissue macrophage differentiation occurs at the expense of CMo-to-blood PMo differentiation. We observed a positive correlation between plasma CSF-1/CCL-2 ratios and blood PMo levels in patients with SCD, underscoring the clinical significance of these two opposing factors in monocyte differentiation. Combined treatment with CSF-1 and anti-P selectin antibody more effectively increased PMo numbers and reduced stasis compared with single-agent therapies in SCD mice. Altogether, these data indicate that monocyte fates are regulated by the balance between two heme pathways, Nrf2/CSF-1 and IFN-I/CCL-2, and suggest that the CSF-1/CCL-2 ratio may present a diagnostic and therapeutic target in SCD.