Production Of Abnormal Hemoglobin Research Articles

Sickle Cell Anemia and Pregnancy Hemolysis: Clinical Considerations

Sickle cell anemia (SCA) is a hereditary blood disorder characterized by abnormal hemoglobin production, leading to chronic hemolysis and episodic vaso-occlusive crises (VOCs). Pregnancy in women with SCA poses significant clinical challenges due to the increased physiological demands, which exacerbate hemolysis and increase maternal and fetal risks. This review explores the pathophysiology of hemolysis in SCA during pregnancy, its clinical implications, and management strategies aimed at improving maternal and fetal outcomes. Hemolysis can result in severe anemia, acute chest syndrome, increased risk of infections, and adverse fetal outcomes, such as intrauterine growth restriction and preterm delivery. Management strategies for hemolysis in pregnancy include blood transfusions, pharmacological therapies, nutritional supplementation, and emerging treatments like gene therapy. Blood transfusions are widely used to mitigate anemia and reduce the number of circulating sickled cells, while pharmacological agents such as L-glutamine help address oxidative stress. Nutritional support, particularly with folic acid and antioxidants, is essential in promoting healthy red blood cell production and mitigating oxidative damage. Emerging therapies like gene editing offer promising future directions for more effective management of SCA and pregnancy-related hemolysis.

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.

Ovarian Tissue Cryopreservation for Fertility Preservation in Patients with Hemoglobin Disorders: A Comprehensive Review.

Hemoglobin diseases like sickle cell disease (SCD) and β-thalassemia (BT) present fertility challenges for affected patients. SCD and BT result from abnormal hemoglobin production or structure and pose numerous health concerns. Despite medical advancements improving the quality of life or even providing cures, SCD and BT pose unique fertility concerns for women. Young women with these disorders already contend with reduced ovarian reserve and a narrower fertile window, a situation that is compounded by the gonadotoxic effects of treatments like medications, transfusions, stem cell transplants, and gene therapy. While crucial for disease control, these interventions may lead to reproductive health issues, increasing infertility and early menopause risks. Ovarian tissue cryopreservation (OTC) offers potential for future motherhood to women with hemoglobin disorders facing infertility related to curative treatments. OTC involves surgically removing, preparing, and freezing ovarian tissue containing primordial follicles capable of producing mature oocytes, offering advantages over oocyte cryopreservation alone. However, the application of OTC for patients with hemoglobin disorders presents unique challenges, including special health risks, financial barriers, and access to care. This comprehensive literature review delves into the current state of ovarian tissue cryopreservation for fertility preservation in patients with hemoglobin disorders. Empowering patients with informed reproductive choices in the context of their hemoglobin disorders stands as the ultimate goal.

Green Synthesis of Phyllanthus Niruri Nanoparticles for the Treatment of Sickle Cell Anemia

Nanotechnology is currently the most active research area in modern materials science. While numerous chemical and physical methods exist for the synthesis of nanomaterials, the green synthesis approach is increasingly prominent. Plant-mediated synthesis of nanoparticles is a green chemical technique that integrates nanotechnology with botany. This novel method of synthesis ideally occurs at ambient temperatures, neutral pH, and is cost-effective and environmentally friendly. Given this goal, various routes have been explored for synthesizing nanomaterials. The present study aims to formulate and evaluate herbal nanoparticles derived from Phyllanthus niruri for the natural treatment of sickle cell anemia. Sickle cell anemia is characterized by the presence of sickle-shaped erythrocytes caused by abnormal hemoglobin production. This condition leads to clogging of capillaries and obstructs blood flow in the vessels, resulting in severe complications such as ischemia, hypoxia, and organ failure. While some drugs, such as hydroxyurea, are available for treating sickle cell anemia, they are often associated with severe adverse effects, limiting their frequent use. Therefore, this study focuses on designing herbal nanoparticles as an alternative treatment for sickle cell anemia. The plant material for this study was sourced from an authorized market, dried, and powdered for further processing.

“The Parental Perspective of Thalassemia in Bangladesh: Challenges for Prevention and Management of Thalassemia”

Introduction: Thalassemia is a genetic blood disorder characterized by abnormal hemoglobin production, poses significant challenges for families worldwide. In Bangladesh, where the prevalence of thalassemia is notable, parents face unique hurdles in both preventing and managing this condition. Aim of the study: The aim of this study is to explore the parental perspective of thalassemia in Bangladesh, focusing on the challenges faced in the prevention and management of the disease. Methods: This was a cross section retrospective study conducted in the Department of Paediatrics of M Abdur Rahim Medical College, Dinajpur, Bangladesh during the period from June 2023 to December 2023. Result: Among the total of 320 caregivers, 46.9% were father, while 53.1% were mother respectively. Minority 14.1% of marriages were consanguineous, while the majority (85.9%) was not. The majority (82.8%) of respondents had one thalassemic child, while 17.2% had two or more thalassemic children. Before the diagnosis of thalassemia in their child, 90.9% of respondents had not heard about thalassemia. All respondents (100%) reported not undergoing thalassemia screening before marriage. The median age at diagnosis of thalassemia among the participants was 1.32 years. Beta thalassemia was diagnosed in 30.6% of the participants, while 68.8% had E-beta thalassemia. The majority 65.9% of respondents correctly identified thalassemia as a genetic disease, while 22.5% provided an incorrect response. Conclusion: Thalassemia presents significant challenges for affected individuals and their families in Bangladesh, ranging from limited access to diagnostic services and blood transfusions to social stigma and financial burdens.

Heme Scavenging by Hemopexin Attenuates Sepsis-Induced Proinflammatory Cytokines and Kidney Insuffciency in a Humanized Mouse Model of Sickle Cell Disease

Sickle cell disease (SCD) is a genetic blood disorder characterized by abnormal hemoglobin production, leading to sickle-shaped red blood cells (RBC). Alteration in RBC shape results in vasoocclusion, chronic hemolysis, and multiple organ damage. One of the severe complications of SCD is an increased susceptibility to infections, including sepsis, which can be life-threatening. Kidney injury, a common and severe complication of sepsis, contributes to the complexity and poor outcomes associated with morbidity and mortality in SCD. However, the mechanisms that underlie septic acute kidney injury (AKI) in SCD are poorly understood. Here, we examined the effects of sepsis in transgenic homozygous SCD (SS; Townes model) mice and their non-sickling (AA) counterparts. We tested the hypothesis that aggravation of inflammation and oxidative stress by free heme released during hemolysis contribute to sepsis-induced kidney insuffciency in SCD. AA and SS mice were subjected to 18 h of sham operation and cecal ligation and puncture (CLP), a pre-clinical model of polymicrobial sepsis, after which kidney function was evaluated by transdermal measurement of glomerular filtration rate (GFR). AKI biomarkers, renal oxidative stress, and cytokines levels were also investigated. We demonstrate that mid- to high-grade CLP (ligation of 60-75% of the cecum and multiple punctures with 21-gauge needles) caused 100% mortality in SS mice. Unlike AA mice (100% survival), SS mice subjected to low-grade CLP (LgCLP; ligation of <45% of the cecum and a single puncture with 21-gauge needles) exhibited 40% survival. LgCLP reduced body weight but did not exacerbate splenomegaly in SS mice. Basal plasma bilirubin, heme, and ferritin were significantly higher in SS than in AA mice. In contrast to AA, LgCLP amplified the increase in plasma bilirubin, heme, and ferritin in SS mice. LgCLP also decreased GFR and increased renal oxidative stress, AKI biomarkers, and kidney-to-body weight ratio in SS mice. Luminex multiplex cytokine analysis indicated that the plasma levels of multiple pro-inflammatory cytokines were elevated in septic SS mice. Heme scavenger hemopexin (HX) diminished LgCLP-induced plasma heme increase. HX also mitigated kidney insuffciency, inflammation, and mortality in the septic SS mice. Our findings suggest that free heme contributes to septic AKI in SCD mice and that HX therapy may attenuate the harmful effect of heme in SCD during sepsis. NHLBI: R01 HL151735. 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.

Frequency Of Beta Thalassemia Major Abo Blood Groups In Different Foundation Of District Peshawar

Background: Thalassemia major (TM) is an inherited hemolytic disorder occur due to abnormal hemoglobin production as a result of HBB (Haemoglobin Subunit Beta) gene mutation because HBB gene provides instructions for making of beta globin. The research study aim is to determine the frequency of beta thalassemia major ABO blood group in different foundation of district Peshawar. Methods: A descriptive cross-sectional study was conducted, involving 100 individuals with Thalassemia major from different foundations in Peshawar, including Hamza Foundation and Fatmid Foundation. The data was analyzed for statistical analysis using SPSS version 22.0 software. Results: The study analyzed the gender-wise distribution of Thalassemia major patients, revealing that out of the 100 individuals, 43 were female (43%) and 57 were male (57%). Moreover, the study examined the ABO blood types among the participants. The most prevalent blood type among the Thalassemia major patients was B+ (35.0%), followed by O+ (34.0%), A+ (26.0%), AB+ (4.0%), and O- (1.0%). Conclusion: Based on the results, it can be said that among those with Thalassemia major in the population under study, the B+ blood type is the most prevalent and well-known ABO blood group.

Abstract 3853: T cell ferroptosis attenuates antitumor immune responses in sickle cell disease

Abstract Background: Sickle cell disease (SCD) is the most common inherited blood disorder and arises from homozygosity for the HbS mutation (GAG>GTG: βGlu6Val) leading to the production of abnormal hemoglobin that cause sickle shaped red blood cells (RBCs). Individuals with SCD are at higher risk than the general population for developing hematologic malignancies or solid tumors such as renal medullary carcinoma (RMC). Although relatively rare, RMC is one of the most aggressive kidney cancers and is the third most common kidney cancer among children and young adults who harbor sickle hemoglobinopathies such as SCD or sickle cell trait (SCT) which occurs due to heterozygosity for the HbS mutation. Molecular profiling studies have shown that most cases involve biallelic inactivation of the SMARCB1 gene, either through simultaneous hemizygous loss and translocation or by homozygous loss. The loss of SMARCB1 and subsequent dysregulation of chromatin remodeling are key factors contributing to the development and progression of renal medullary carcinoma. Despite manifesting an inflamed tumor immune microenvironment, RMC consistently demonstrates resistance to conventional immune checkpoint inhibitors (ICI). Ameliorating the efficacy of immunotherapy of RMC is vital for research and potential therapeutic interventions by targeting CD8+ T cells. Methods: CyTOF was performed by using the spleen of WT mice and SCD mouse model. mRNA was isolated from CD8+ T cells of Peripheral Blood Mononuclear Cell (PBMC) collected from healthy donors and SCD patients followed by bulk RNA sequencing. Hi-C was conducted using CD8+ T cells isolated from PBMC of healthy donors and SCD patients. We employed DNA FISH (Fluorescence in Situ Hybridization) to examine alterations in gene architecture within CD8+ T cells under varying conditions. Results: RMC tumors exhibit accelerated tumor growth and reduced numbers of tumor resident CD8+ T cells in SCD mice model compared with WT control. CD8+ T cells in the SCD associated tumor microenvironment (TME) are subjected to ferroptosis by downregulation of SLC7A11; however, SMARCB1 loss promotes the resistance of RMC tumor cells to ferroptosis. Genomic architecture of CD8+ T cells is altered under SCD conditions, potentially contributing to immune dysfunction. Conclusions: Our research has identified significant alterations in the 3D genome architecture of CD8+ T cells in individuals with SCD. These alterations lead to transcriptional inhibition of SLC7A11, resulting in CD8+ T cell ferroptosis and a hindered anti-tumor immune response in RMC. These findings elucidate the mechanistic relationship of SCD with ICI resistance in cancers such as RMC and provide novel avenues for therapeutically sensitizing tumors to immunotherapies in individuals with SCD. Keywords: Sickle Cell Disease, Renal Medullary Carcinoma, SMARCB1, Ferroptosis, Genomic Architecture Alteration, Hi-C, SLC7A11 Citation Format: Zilong Zhao, Benxia Hu, Yalan Deng, Melinda Soeung, Giannicola Genovese, Wenbo Li, Pavlos Msaouel, Liuqing Yang, Chunru Lin. T cell ferroptosis attenuates antitumor immune responses in sickle cell disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3853.

Iron Restricted Erythropoiesis Under Hepcidin Mimetic Treatment (PN23114) Improved Disease Parameters in a Mouse Model for Sickle Cell Disease

Sickle Cell Disease (SCD) is an inherited hemolytic disorder that results from a single point mutation in the hemoglobin-beta (HBB) gene that encodes for the beta-globin subunit of hemoglobin, causing the production of abnormal hemoglobin S (HbS). HbS polymerizes under low oxygen conditions, causing sickling effects on red blood cells (RBCs). Sickling of RBCs initiates vaso-occlusion, downstream inflammatory responses, and hemolysis (Zhang D, et al., Blood. 2016;127:801-9). Previous studies have shown that polymerization under low oxygen conditions is extremely sensitive to HbS concentrations within the RBCs (Hofrichter J, et al, Proc Natl Acad Sci USA. 1974;71:4864-8; Sunshine HR, et al. Nature. 1978;275:238-40). Controlling iron delivery for erythropoiesis provides a mechanism to potentially down-modulate the HbS concentration, thereby reducing the potential for HbS polymerization and sickling of RBCs (Parrow NL, et al., Blood. 2021;137:1553-5). The potent hepcidin mimetic peptide PN23114 targets the iron exporter membrane protein ferroportin to trigger its degradation, thus preventing iron export from cells. We hypothesize that the resulting pharmacodynamic effect of limiting iron availability for erythropoiesis should reduce HbS concentrations within the RBCs that may prevent sickling and hemolysis. Townes mice (genetically altered to contain the human SCD HbSS homozygous mutation) are a well-established experimental model for human SCD (Li-Chen W, et al., Blood. 2006;108:1183-8). They exhibit severe hemolysis as indicated by elevated bilirubin and lactate dehydrogenase (LDH) levels, and a shortened RBC half-life compared to wild type (WT) mice. These mice also develop vaso-occlusive events and elevated inflammatory responses (for example, increases in peripheral blood white blood cell [WBC] and neutrophil counts). To test whether iron restriction mediated by a hepcidin mimetic may alter outcomes in this model, PN23114 was administered subcutaneously to Townes HbSS mice. Mice were treated over 4-weeks (3 times weekly) with vehicle or PN23114 at 1 or 2.5 mg/kg (vehicle treated WT mice served as controls). At the end of 4 weeks, total bilirubin was elevated in the HbSS-vehicle group compared to WT-vehicle (Figure 1A). Total bilirubin was dose-dependently reduced by PN23114 treatment compared to the HbSS-vehicle group (Figure 1A). LDH was also elevated in the HbSS-vehicle group and was dose-dependently reduced with PN23114 treatment (557±105 units/L in WT-vehicle, 809±145 units/L in HbSS-vehicle, 611±341 units/L in HbSS-PN23114-1mg/kg and 372±71 units/L in HbSS-PN23114-2.5mg/kg groups). Peripheral blood WBC counts were dose-dependently reduced by PN23114 treatment compared to HbSS-vehicle (Figure 1B), with concomitant decreases in peripheral blood neutrophil counts. Reduction in hemoglobin values was observed with PN23114 treatment in HbSS (5.9±0.9 g/dL in HbSS-1mg/kg group and 4.4±0.4 g/dL in HbSS-2.5 mg/kg group) compared to the HbSS-vehicle group (7.1±0.3 g/dL). These results suggest that pharmacologic iron restriction with PN23114, a hepcidin mimetic peptide, led to a reduction in hemolysis and inflammatory markers in a SCD model. Therefore, a hepcidin mimetic therapeutic could potentially be a novel approach to prevent hemolysis, inflammation and downstream clinical complications associated with human SCD.

Comparative Analysis of Hematological Parameters in Indian Sickle Cell Anemia Patients Treated with Low Dose (10mg/kg/day) Versus Standard Dose (20mg/kg/day) Hydroxyurea

Introduction: Sickle cell anemia (SCA) is a hereditary genetic disorder characterized by the production of abnormal hemoglobin (HbS), which leads to altered physiological properties. Hydroxyurea (HU) is an established oral drug that has demonstrated the ability to ameliorate the severity of the disease mainly by increasing the production of fetal hemoglobin (HbF), thereby reducing sickle cell crises. Studies in the Indian population have shown positive clinical outcomes with a low dose (10 mg/kg/day) of hydroxyurea. Low dose is recommended by most of the physicians in India due to fear of adverse events and noncompliance of patients for regular monitoring of blood parameters. However, the effectiveness of low-dose HU compared to the standard dose (20 mg/kg/day) in reducing sickle cell anemia crises remains uncertain due to the diverse clinical severity of SCD in the Indian population. To address this question, the study aimed to conduct a national level randomized control trial involving SCA patients from various ethnic backgrounds to definitively establish the benefits of low-dose HU for Indian patients compared to the standard dose. Materials and Methods: Till date the study enrolled 140 sickle cell anemia patients (2-14 years) after informed consent. Patients were randomly assigned to either low (ARM 1: 10 mg/kg/day) or standard (ARM 2: 20 mg/kg/day) doses of hydroxyurea. 37 patients had been followed up for 6 months' time point of hydroxyurea therapy. Three ml of whole blood samples were collected in K2-EDTA tube, anthropometric details and clinical parameters of patients were studied. Results: 18 participants were allotted ARM 1 with a mean age of 8.9 ± 2.8 years and 19 were allotted ARM 2 with a mean age of 8.6 ± 2.5 years. All patients were followed upto 6 months after hydroxyurea treatment. The clinical severity was classified as class 1 and class II based on the clinical events of patients. It was found that 26 patients are classified under the class I category of severity while 10 patients classified under the class II category of severity. 6(60%) participants with baseline HbF level below 15% had Class II severity whereas 3(11.5%) participants with baseline HbF level of more than 15% had Class II severity. The effect of hydroxyurea dose on haematological indices was also studied which revealed that there was significant decrease in WBC, platelet count by 2.18 ± 2.24 10 3/µl, 24 ± 136.6 10 3/µl in ARM 1 compared to ARM II 4.08 ± 2.6 10 3/µl, 50 ± 127.39 10 3/µl. A rise in hemoglobin level by 0.18 ± 0.71 gm/dl in ARM I, 0.71 ± 0.77 gm/dl in ARM II and MCV by 3.29 ± 2.61 fl in ARM1, 5.28 ± 3.57 fl in ARM II. The difference was found statistically significant in both the ARMS. (P<0.001). The RBC count in patients did not show a significant elevation in both the ARMS. The absolute neutrophil count in patients were significantly reduced in ARM II by 2874 ± 1748 per µl compared to 1963 ± 1748 per µl in ARM I. Two patients in ARM II showed a reduced ANC level below 1000 thus, hydroxyurea therapy among those two patients was stopped and resumed after a week. Interestingly the rise in HbF was significantly higher in ARM II by 4.81 ± 2.71 % compared to 1.55 ± 2.32 % in ARM I. The critical clinical events such as VOC, Stroke, ACS was not observed in patients at baseline and after 6 months of HU follow up. Conclusion: The study demonstrated that hydroxyurea treatment in sickle cell anemia patients led to a significant increase in HbF levels in ARM II compared to ARM I. Haematological parameters like WBC Count, platelets, ANC was significantly lower in ARM II with 2(10.5%) of patients in ARM II having ANC below 1000 warranting close monitoring during treatment. Furthermore, the absence of critical clinical events during the 6-month follow-up period suggests the potential benefits of hydroxyurea therapy in managing sickle cell anemia in both ARMS with a long term follow up providing more accurate results to arrive at conclusion.

The Quality of Life of Sickle Cell Disease Patients in Saudi Arabia 2023

The quality of life of sickle cell disease patients in Saudi Arabia 2023. Sickle cell disease (SCD) is a genetic blood disorder that affects millions of people around the world. It is caused by a mutation in the hemoglobin gene that results in the production of abnormal hemoglobin, which is the protein responsible for carrying oxygen in the blood. SCD is relatively common in Saudi Arabia, with a prevalence of around 2.3%, while the carrier state for SCD, sickle cell trait (SCT), is estimated to be 3.1%. The southern region of the country has the highest prevalence of both SCD and SCT, followed by the eastern region, with lower rates in the central and northern regions. The high prevalence of SCD and SCT in Saudi Arabia poses significant challenges to the healthcare system, with individuals experiencing complications such as pain crises, infections, and stroke, leading to increased hospitalizations and costly treatments. The government has taken steps to address this issue through newborn screening programs and comprehensive care provision, but further efforts are required to ensure equitable access to healthcare for all affected individuals. The disease can have a significant impact on the quality of life of patients due to its chronic nature, pain, and complications. In this study, we aimed to comprehensively investigate various aspects of SCD patients' experiences in Saudi Arabia. We explored the experiences of SCD patients, focusing on their encounters with pain, hospitalizations, and interactions with healthcare providers, the impact of SCD on the social lives and relationships of patients and the educational and support needs of both SCD patients and their families By addressing these research objectives, we gain a comprehensive understanding of the challenges and needs of SCD patients in Saudi Arabia, ultimately contributing to the development of more patient-centered and effective care strategies. Data Collection methods, instruments used, measurements: Patients were recruited through treating doctors during routine consultations utilizing an online based comprehensive survey. Result: The recruitment period for this study was from March 1, 2023, to the end of June of the same year. A total of 75 patients participated in the survey. However, only 50 responses were included in the analysis due to missing or conflicting data found in the excluded answers. The median age of the surveyed patients was 28 years, indicating an improvement in the care provided compared to previous published articles. Among the participants, 66.7% were males, and all the responses came from individuals affected by the disease. The majority of the patients (83.3%) resided in the southern region of the kingdom, followed by (16.7%) from the eastern region. Regarding patient support, all included participants stated that their support came solely from their families, as they declined any support from other patients, religious groups, or healthcare professionals. The main sources of support were the parents, followed by life partners and siblings. Although the patients expressed satisfaction with their family support, (50%) were unsure if support from outside the family was necessary. Regarding pain status, 50% of the patients reported experiencing pain more than three times in the last six months. Medical attention was sought in 50% of these cases, and 33.3% of the attacks required admission. In managing their crises, all patients used opioid-based analgesics. However, only (66.7%) used hydration in addition to home remedies, hot compressions, and local treatments, while (16.7%) used non-opioid-based medications. Despite experiencing emotional distress due to the disease symptoms, anxiety, and feelings of being dismissed, none of the patients sought emotional support from certified professional personnel. The disease had a notable impact on the professional lives of the patients, with 50% being unemployed, and others considering quitting their jobs, refusing promotions, or needing job assistance. The treatment goals from the patients' perspective were to reduce disease complications, improve their quality of life, and decrease pain crises and hospital admissions. Unfortunately, less than 49% of the patients achieved these treatment goals with the provided medications.

Studi Literatur: Kualitas Hidup Anak Usia Sekolah dengan Thalasemia

Thalassemia major is a hematological single gene disorder that is inherited and can cause anemia in affected children, the impact of which in the world is a major public concern in Southeast Asia, including Indonesia. Indonesia is one of the countries in the thalassemia belt. In Indonesia, thalassemia major is more common and a serious health problem; about 3 – 10% of people carry the thalassemia gene due to abnormal hemoglobin production. More frequent visits to the hospital have a negative impact on children's lives in terms of physical burden, psychological burden and scholastic performance. The method used in this study is Literature review, method journal search using PICOT description and journal selection using Prism Diagram. Results of literature study in this study, the outcome as measured by PedsQL was quality of life. Questions were categorized into 4 domains: physical health, emotional health, family function and support and school and career functioning. In this study, we found that the HRQoL scores of TDT patients were higher in all dimensions compared to scores of similar studies. According to the results of several studies conducted, using the PedQL 4.0 instrument in pediatric and adolescent patients, either by distributing the instrument or by good interview technique. to patients and parents resulted in patients having a higher HRQoL in the psychosocial domain and the lowest in the education domain. This low value can be related to frequent visits to the hospital for blood transfusions or iron chelation therapy treatment so that children cannot go to school because of their perceived weakness and do not have sufficient energy to participate in school activities. So that children who do not go to school experience cognitive decline which has a negative impact on their quality of life.

Impact of Hydroxyurea Therapy in Reducing Pain Crises, Hospital Admissions, and Length of Stay Among Sickle Cell Patients in the Eastern Region of Saudi Arabia.

Background In Saudi Arabia, sickle cell disease (SCD) is a major public health issue, especially in the eastern region. Sickle cell patients have major health-related issues, resulting in a poor quality of life and increased morbidity. Abnormal hemoglobin production in SCD causes various complications, such as vaso-occlusive crises, hemolytic episodes, and acute chest syndrome. These disease manifestations increase the need for hospital admission and long-term care. Most therapies for SCD are supportive and include episodic red blood cell transfusions, narcotics, antibiotics, and intravenous fluids. Hydroxyurea is a disease-modifying therapy. This study aimed to assess the effectiveness of hydroxyurea therapy on reducing pain crises, hospital admissions, and length of stay for SCD patients and discern reasons that would prevent SCD patients from using hydroxyurea as a treatment option. Methodology We conducted a descriptive cross-sectional study on SCD patients from the eastern Saudi Arabian province. The study included 202 SCD patients from hematology clinics and medical wards. We used a validated questionnaire tested for reliability after a pilot study of 15 randomly selected patients. We surveyed participants on demographic data, use of hydroxyurea, compliance with the regimen, hospitalization rates, durations, and complications. The study used IBM SPSS Statistics for Windows, Version 22.0. (IBM Corp., Armonk, NY) to analyze the data. All statistical analysis was done using two-tailed tests. P-values < 0.05 were considered statistically significant. Results The study included 202 participants who agreed to participate and completed the study questionnaire. The respondents comprised 150 SCD patients (74.3%) and 52 caregivers of SCD patients (25.7%). Patient ages ranged from one year to older than 36 years (mean age: 26.8 ± 12.3 years). The most common reason for not using hydroxyurea was that it was never offered to patients as a treatment option (40.9% of respondents), followed by respondents who had never heard of it (34.4%), think that they do not need it (24.7%), and fears of long-term consequences (23.7%). More hydroxyurea users (35.1%) suffered no acute painful crises during the last year than nonusers (32%), and more nonusers suffered more than four crises (20%) than hydroxyurea users (9.1%; p=.046). As for hospitalization due to SCD-related complications, 66.2% of hydroxyurea users were never hospitalized, while 51.2% of nonusers were never hospitalized. While 19.5% of hydroxyurea users were hospitalized one to two times, 28.8% of nonusers were hospitalized one to two times (p=.049). Conclusions The study revealed that hydroxyurea is effective in reducing painful vaso-occlusive crises and the number of hospital admissions. The prevalence of hydroxyurea use among SCD patients in the eastern province of Saudi Arabia remains low. Therefore, education campaigns and programs to increase awareness among health care providers regarding the benefits of hydroxyurea use are warranted in our region to help improve patient outcomes.

The Impact of Optical Coherence Tomography in the Early Identification of Children with Sickle Cell Retinopathy.

Introduction Sickle cell disease is characterized by the production of abnormal hemoglobin, which affects hemoglobin molecule stability during hypoxia and leads to the formation of sickle cells, resulting in increased hematic viscosity, hemolysis, and microvascular blockage. Vasoocclusion is assumed to be the primary cause of vision-threatening retinopathy in sickle cell disease. The aim of this study was to improve the early detection of sickle cell retinopathy (SCR) in children with sickle cell disease (SCD) and investigate the link between systemic and ocular symptoms. Methods This cross-sectional study comprised children with SCD. The patient files provided a detailed medical history. The laboratory tests included a blood count, reticulocyte count, and Hb electrophoresis. The slit lamp, fundus, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) were all part of the ophthalmological examination. Results The study comprised 15 children with sickle cell disease who met the inclusion and exclusion criteria, with a mean age of 11.15 ± 1.29 years. Nine of the children were males (60%) and six were females (40%). 8 (53.3%) of the children had Hb SS, three (20%) had Hb SC, three (20%) had Hb SB+, and one (6.7%) had Hb SB0. Four children (26.7%) had poor visual acuity. A fundus examination revealed significant abnormal findings in 12 of the 7 children's eyes (40 percent). Macular thinning was detected by OCT in 10 eyes of 7 children (33.3%). Flow voids at the deep retinal capillary plexus were detected by OCTA in 10 eyes of 7 children (33.3%). Longer disease duration, higher reticulocytic percent, more painful crises, and noncompliance with hydroxyurea medication were all linked to the existence of eye abnormalities on fundus examination and OCT. Conclusion OCTA can show early retinal damage in sickle cell patients with macular changes. Sickle cell retinopathy is usually associated with more severe disease.

Sickle cell disease: The importance of awareness and early detection of ocular manifestations

World Sickle Cell Awareness Day is celebrated every June 19 to raise awareness for sickle cell disease (SCD). Access to health services remains unequitable in countries affected by the disease and stigma surrounding patients hinders access to therapies. SCD is the most common severe monogenic disease in the world and is characterized by abnormal hemoglobin production. Major complications include vaso-occlusive events, hemolytic anemia, and inflammation. Microvascular events in the eye are namely responsible for sickle cell retinopathy with or without vasoproliferative changes. Methods included the electronic search of peer-reviewed English literature published until 2021, which was screened, appraised in full version, and incorporated into the review as deemed necessary. This review provides a summary of disease mechanisms and ocular manifestations, and highlights the importance of early diagnosis, close management with imaging technology, and therapeutic avenues for patients with SCD. In addition to significant healthcare barriers encountered by patients and their families, early diagnosis for SCD must be posed by physicians. It is crucial for the healthcare community to become better familiarized with the disease manifestations for early recognition and prevention of chronic complications and morbidity.

Newborn Screening Practices for Beta-Thalassemia in the United States.

Beta-thalassemia, a heritable condition of abnormal hemoglobin production, is not a core condition on the United States Recommended Uniform Screening Panel (RUSP) for state and territorial newborn screening (NBS) programs. However, screening for sickle cell disease (which is on the core RUSP) also detects reduced or absent levels of hemoglobin (Hb) A and certain other Hb variants associated with beta-thalassemia and, thus, allows for a timely referral to appropriate healthcare to minimize sequalae of the disease. The Association of Public Health Laboratories’ Hemoglobinopathy Workgroup administered a comprehensive survey of all U.S. NBS programs to assess beta-thalassemia testing methodologies, the cutoffs for defining beta-thalassemia major, and the reporting and follow-up practices. Forty-six (87%) of the programs responded. Thirty-nine of the 46 responding programs (85%) report some form of suspected beta-thalassemia; however, the screening methods, the percentage of Hb A used as a cutoff for an indication of beta-thalassemia major, and the screening follow-up vary widely. The standardization of technical and reporting procedures may improve access to specialty care prior to severe complications, increase genetic counseling, and provide data needed to better understand the public health impact and clinical outcomes of beta-thalassemia in the United States.

The Role of miRNAs as Therapeutic Tools in Sickle Cell Disease.

Background and Objectives: Sickle cell disorder (SCD) is a paradigmatic example of a complex monogenic disorder. SCD is characterized by the production of abnormal hemoglobin, primarily in the deoxygenated state, which makes erythrocytes susceptible to intracellular hemoglobin polymerization. Functional studies have affirmed that the dysregulation of miRNAs enhances clinical severity or has an ameliorating effect in SCD. miRNAs can be effectively regulated to reduce the pace of cell cycle progression, to reduce iron levels, to influence hemolysis and oxidative stress, and most importantly, to increase γ-globin gene expression and enhance the effectiveness of hydroxyurea. Results: This review highlights the roles played by some key miRNAs in hemoglobinopathies, especially in hematopoiesis, erythroid differentiation, and severity of anemia, which make miRNAs attractive molecular tools for innovative therapeutic approaches. Conclusions: In this era of targeted medicine, miRNAs mimics and antagomirs may be promising inducers of HbF synthesis which could ameliorate the clinical severity of SCD.

Pretransfusion Hemoglobin F Level in Thalassemia Patients: Effect of Well-Balanced Versus Poor Transfusion

Background: Thalassemia is a common condition in Iraq. More than ten thousand patients registered in Iraq. If well-balanced hypertransfusion regimen to maintain pretransfusion hemoglobin level above the internationally agreed 9.0 gm/ dL could suppress the patients‘ bone marrow and shutdown the hematopoiesis to the extent of not producing any hemoglobin F. Patients and Methods: One hundred well-balanced transfusion-dependant thalassemia patients were evaluated for Hemoglobin F level prior to their scheduled transfusions. Hemoglobin level must have been more than 9.0 gm/ dL to qualify the patient to be entered into this group. All such patients must have showed minimal skeletal changes of thalassemia. Another hundred patients with frank features of thalassemia and poor history of blood transfusion were also enrolled in the study. We aimed at knowing whether HbF is significantly different in the two groups. It could indicate that patients‘ bone marrow could be totally turned off and no abnormal hemoglobin will be allowed to be produced. Results: Seventy nine percent of our enrolled transfusion-dependent thalassemia patients who fulfilled the criteria and were well managed showed correction of their HbF level to near zero! Thirty five percent of the poorly transfused patients also corrected their abnormal HbF level. Conclusions: This study showed that marrow micromilieu could be manipulated in patients with thalassemia in such a way so as to totally shutdown production of abnormal hemoglobin F as a result of provision of normal hemoglobin through blood transfusion. The fact that even one third of poorly transfused patients could show the same results indicates that any degree of transfusion support will have its impact on the marrow.

A case of severe multi-system disease in a sickle cell SC patient caused by parvovirus B19 infection

Sickle Cell Disease (SCD) is an inherited hemoglobinopathy, which results in production of abnormal hemoglobin S. HbSC disease is a variant of SCD, which shares a similar clinical complication profile to HbSS disease, but often thought to be a milder condition. In patients with SCD, Hb S in deoxygenated state undergoes polymerization, leading to hemolysis, vaso-occlusive events, and eventually end-organ damage. Among other complications in patients with SCD is increased risk of complications caused by parvovirus B19. We present a case of a 14-year-old female with HbSC disease who presented to the emergency room with complaint of abdominal pain and found to have splenic sequestration. Splenic sequestration progressed rapidly, Hemoglobin (hb) dropped to 4.6 g/dl and acute chest syndrome (ACS) developed. She was treated following the ACS protocol, received 4 units of Packed Red Blood Cells (PRBC) and subsequently underwent a single volume PRBC exchange transfusion. Considering her unusual presentation, with severe ARDS from alveolar hemorrhage requiring mechanical ventilation and multi-organ injury, several autoimmune and infectious conditions with a cytokine storm component including COVID-19 disease, were considered. Results of viral testing revealed parvovirus B19 IgM antibodies signifying an acute infection. She fully recovered with supportive care and was discharged home. Multisystem involvement simulating connective tissue disorders or malignancies with acute parvovirus B19 infection has been reported and is considered extremely rare. To our knowledge, there were no reports of pediatric patients with SC disease presenting with splenic sequestration and ACS in the setting of parvovirus B19 multisystem disease. Keywords: sickle cell disease; acute respiratory distress syndrome; acute chest syndrome; parvovirus B19.

Techniques for the Detection of Sickle Cell Disease: A Review.

Sickle cell disease (SCD) is a widespread disease caused by a mutation in the beta-globin gene that leads to the production of abnormal hemoglobin called hemoglobin S. The inheritance of the mutation could be homozygous or heterozygous combined with another hemoglobin mutation. SCD can be characterized by the presence of dense, sickled cells that causes hemolysis of blood cells, anemia, painful episodes, organ damage, and in some cases death. Early detection of SCD can help to reduce the mortality and manage the disease effectively. Therefore, different techniques have been developed to detect the sickle cell disease and the carrier states with high sensitivity and specificity. These techniques can be screening tests such as complete blood count, peripheral blood smears, and sickling test; confirmatory tests such as hemoglobin separation techniques; and genetic tests, which are more expensive and need to be done in centralized labs by highly skilled personnel. However, advanced portable point of care techniques have been developed to provide a low-cost, simple, and user-friendly device for detecting SCD, for instance coupling solubility tests with portable devices, using smartphone microscopic classifications, image processing techniques, rapid immunoassays, and sensor-based platforms. This review provides an overview of the current and emerging techniques for sickle cell disease detection and highlights the different potential methods that could be applied to help the early diagnosis of SCD.