Regular Blood Transfusions Research Articles

Cognitive performance, mental health, and quality of life in β-thalassemia individuals: a comprehensive analysis

IntroductionBeta-thalassemia is a prevalent autosomal recessive haemolytic disorder, particularly in the Middle East. Patients with beta-thalassemia major (βTM) require iron chelation therapy and regular blood transfusions, while those with beta-thalassemia intermedia (βTI) exhibit milder symptoms. This study aimed to evaluate cognitive function, behavioural problems, quality of life, and related aspects in individuals with βTM and βTI.MethodsThe cross-sectional study included 20 βTM participants, 20 βTI participants, and 19 healthy controls. Participants underwent psychiatric interviews, the Wechsler Adult Intelligence Scale (WAIS-III), Symptom Checklist-90 Revised (SCL-90R), and Short-Form Health Survey (SF-36). Clinical data and laboratory investigations were also collected.ResultsβTM participants exhibited lower vocabulary and picture completion scores on the WAIS-III compared to other groups. βTI participants had significantly higher scores on SCL-90R subscales for somatization, depression, anxiety, paranoid ideation, and psychoticism. Both patient groups reported poorer quality of life across all SF-36 domains compared with controls. Longer disease duration correlated with lower levels of somatization, interpersonal sensitivity, depression, anxiety, and paranoid ideation. Less frequent blood transfusions were associated with better physical and mental health summary scores but also higher somatization. Elevated serum iron levels corresponded with increased anxiety, hostility, and psychoticism symptoms, while higher serum ferritin related to more obsessive–compulsive behaviours but less somatization and psychoticism.ConclusionsIndividuals with thalassemia exhibit cognitive deficits, psychological disturbances, and diminished quality of life, with distinct patterns depending on disease severity. Regular monitoring and appropriate interventions are crucial for optimizing their overall well-being and functioning.

Molecular and haematological characterisation of haemolytic anaemia associated with biallelic KLF1 mutations: a case series

AimsKrüppel-like factor 1 (KLF1) is an erythroid-specific transcription factor playing an important role in erythropoiesis and haemoglobin (Hb) switching. Biallelic KLF1 mutations can cause haemolytic anaemia with thalassaemia-like syndromes but...

Plasma sphingomyelin levels were negatively correlated with ferritin levels in splenectomized thalassemia patients

Abstract Beta thalassemia results from decreased production of beta chains due to either mutations or deletions in the beta-globin gene, leading to impaired production of hemoglobin A. Thalassemia patients take frequent blood transfusions to compensate for hemolytic anemia and iron overload. Iron overload is monitored by serum ferritin levels in these patients. Extra-medullary hematopoiesis in beta thalassemia major leads to hypersplenism which often necessitates splenectomy to increase red cell life span and decrease transfusion need. Sphingomyelin is the second most abundant phospholipid in human plasma after phosphatidylcholine. In contrast to the well-defined roles of sphingolipids in cell membranes, their possible physiological role in lipoprotein metabolism has recently gained attention. Increased circulating levels of sphingomyelins and ceramides were observed in obesity, diabetes, and cardiovascular diseases. Although lipid abnormalities such as hypocholesterolemia and relatively increased triglycerides were reported in beta-thalassemia patients, there is no study investigating sphingolipid levels in thalassemia. Therefore, we investigate certain long chain and very long chain sphingomyelins and ceramides in beta-thalassemia patients who are under routine follow-up in our hospital. Thalassemia major patients who applied to the hospital for regular blood transfusion and gave consent were included in the study. Blood samples were obtained before transfusion. Plasma sphingomyelin (C16, C18 and C24) and ceramide (C16, C18, C20, C22, C24) species were measured by triple quadruple LC-ESI-MS/MS (Shimadzu, Japan). D-erythrosphingosine-D9 (Matreya) was used as an internal standard, all other lipid standards were from Avanti. Body iron stores of the patients were monitored by serum ferritin levels. A total of thirty patients were included in the study. All patients typically received regular erythrocyte suspension transfusions every three weeks and continuous oral iron chelation therapy. Twenty of the patients had a previous splenectomy. The mean age was 34.5 ±8.1 years in the splenectomy group and 32.8 ±8 years in the group without splenectomy. Mean ferritin levels were not different between the groups, being 1073.2±563.5 µg/L in splenectomy and 1709 ±1660.4 µg/L in non-splenectomy groups. All measured sphingolipid levels were similar between splenectomy and non-splenectomy groups. When correlation analysis was performed between measured sphingolipid and ferritin levels, significant negative correlations were found between sphingomyelin C16 (r= -0.591 p<0.006) and C18 (r= -0.594 p<0.006) with ferritin levels in the splenectomy group. However, this negative correlation was absent in the non-splenectomy group. In conclusion, we found that iron overload is associated with lower plasma sphingomyelin levels in splenectomized thalassemia patients. We have been working on the lipidomic analysis of the plasma and erythrocytes of thalassemia patients and other hemolytic anemias. The results may further help to get a better picture of lipid metabolism in thalassemia.

Differential gut microbiota composition in β-Thalassemia patients and its correlation with iron overload

Recent research highlights the significant impact of the gut microbiota on health and disease. Thalassemia, a hereditary blood disorder, requires regular blood transfusions, leading to an accumulation of iron in the body. Such changes could potentially alter the intestinal microbiota, thereby increasing the susceptibility of thalassemic patients to infection. In this study, we analyzed the fecal microbiota of 70 non-transfusion-dependent (NTDT) β-thalassemia/HbE patients and 30 healthy controls. Our findings indicate that iron chelation intervention had no detectable effect on the microbiome profile of thalassemic patients. However, the cross-sectional analysis revealed that the bacterial diversity and community structure in patients were significantly less diverse and distinct compared to those of healthy subjects. Using reference frames, we were also able to demonstrate that bacterial taxa that are known to produce short chain fatty acids, from the genera Alistipes, Coprococcus, and Oscillospira, and those from the family Ruminococcaceae, were less prevalent in the patients. In contrast, bacterial taxa associated with an unhealthy gut, including the genus Clostridium and those from the families Fusobacteriaceae, Enterobacteriaceae, and Peptostrptococcaceae, were more prevalent in patients and found to be correlated with higher levels of ferritin. Collectively, these changes in the microbiota could be regarded as markers of raised ferritin levels, and therefore, awareness should be exercised as they could interfere, albeit indirectly, with the treatment of the co-morbidities of thalassemia.

Transfusion burden and willingness to pay for temporary alleviation of anemia status in transfusion-dependent beta-thalassemia patients in China

BackgroundTransfusion-dependent β-thalassemia (TDT) is one of the global public health concerns highlighted by the World Health Organization. Patients with TDT require regular blood transfusion to survive. However, the availability of blood resources is extremely limited. The purpose of this study was to investigate transfusion burden and willingness to pay (WTP) for temporary remission of anemia status among patients with TDT and to explore the associated factors.MethodsAdult patients with TDT were recruited through cluster sampling across several high-incidence provinces in China. Consenting patients completed online questionnaires on demographic information, transfusion burden and WTP with real-time WeChat communication assistance from researchers. The guiding techniques of double-bounded dichotomous choices and open-ended questions in the contingent valuation method (CVM) were used to obtain participants’ WTP for 1 unit of leukocyte-depleted red blood cells. WTP calculations were performed using maximum likelihood estimation, with further insights gained through subgroup analysis based on gender, family monthly income level and convenience of blood transfusion.ResultsThe analysis included 149 TDT patients from five high-incidence provinces, with an average monthly income of $198.5. Patients received an average of 3.7 units per transfusion, 15.4 times annually, with an average WTP of $70.4 per unit (95% CI [62.0, 78.9]). Estimated WTP for temporary anemia alleviation per transfusion totaled $260.6, exceeding monthly income by 1.32 times. Higher WTP was observed among males, higher-income households, and those with at least junior education. Lower WTP was noted among patients with lower transfusion volumes and those needing to travel for transfusion or during hospitalization for blood transfusion.ConclusionHigh WTP indicated a strong desire for temporary anemia relief. Most TDT patients faced significant economic and transfusion burden. The evident gap in meeting clinical needed underscores the urgent demand for innovative treatments to reduce transfusion dependency, potentially transforming TDT care and improving socioeconomic well-being and clinical outcomes. These findings supported evidence-based decision-making for TDT pharmacoeconomics and efficient healthcare resource allocation in China.

Vitamin D Deficiency among Blood Transfusion-Dependent Beta Thalassemia Children Admitted to Tertiary Level Pediatric Hospital in Nepal: A Descriptive Cross-Sectional Study

Introduction: Children with beta thalassemia are on regular blood transfusions, which could result in iron deposition in the liver causing decreased synthesis of Vitamin D-25OH. There are limited publications on the association of Vitamin D deficiency with blood transfusion-dependent thalassemia in the Nepalese population. This study aims to determine the prevalence of Vitamin D deficiency among blood transfusion-dependent beta-thalassemia patients.Methods: This was a descriptive cross-sectional study conducted among beta-thalassemia major patients under 15 years of age, receiving regular blood transfusion, from July 17, 2022, to July 16, 2023, after ethical approval obtained from Ethical Review Committee, Kanti Children’s Hospital (reference number 155). Data were collected using convenience sampling, and descriptive analyses were performed using Microsoft Excel and Statistical Package for Social Sciences (SPSS) 2024.Results: A total of 127 blood transfusion-dependent beta-thalassemia major patients were included in the study, of whom 82 (64.56%) were male. Among these patients, 104 (81.88%) were aged between 5 and 14 year. Almost one-third 41 (32.28%) had Vitamin D insufficiency, and a quarter, 34 (26.77%), had Vitamin D deficiency. Ten percent of the children were underweight, and a quarter were stunted.Conclusions: Children with blood transfusion dependent beta thalassemia major are at a greater risk for Vitamin D deficiency and iron overload

Prevalence of Hypothyroidism in Children with Transfusion Dependent Thalassemia Patient Attending in A Tertiary Care Hospital of Bangladesh

Background: Blood transfusions and iron chelation are standard treatments for β-thalassemia major and Hb E-Beta-Thalassemia. However, repeated transfusions raise body iron levels, leading to secondary hemosiderosis and complications in the heart, endocrine system, and liver. Thyroid dysfunction results from gland infiltration, chronic hypoxia, free radical damage, and iron overload. This study aimed to find out the prevalence of hypothyroidism in transfusion-dependent thalassemic children attending Bangladesh Shishu Hospital & Institute. Methods: A descriptive cross-sectional study was conducted at the Thalassemia Centre, Department of Hematology and Oncology, Bangladesh Shishu Hospital & Institute, from December 2019 to November 2020. The study included 140 children with thalassemia, aged 5 to 16 years, who were receiving blood transfusions. Data were collected using a structured questionnaire with participant consent. Statistical analysis was performed using SPSS version 23.0. Results: In this study, hypothyroidism was observed in 26.2% of patients, with 23.5% having subclinical and 2.9% overt hypothyroidism. In most of the patients (n=85), aged 11-16 years, 58.3% had normal thyroid function, 36.5% had subclinical, and 4.7% had overt hypothyroidism, which was statistically significant (p<0.05). Of the 91 patients with hemoglobin levels below 11.5 g/dL, 85.7% had normal thyroid function, 13.2% had subclinical hypothyroidism, and 1.1% had overt hypothyroidism, also significant (p<0.05). In the group with ferritin levels of 1200-2000 ng/mL, 78.1% had normal thyroid function, 18.8% had subclinical hypothyroidism, and 3.1% had overt hypothyroidism, which was not statistically significant (p>0.05). Conclusion: Subclinical hypothyroidism is commonly seen in thalassemia patients aged 5 to 16 years who undergo regular blood transfusions. Regular physical exams and thyroid function assessments are crucial to detect overt hypothyroidism early. Timely hormone replacement can

Attenuation of TNF-α and Iron Levels in Renal Hemosiderosis by Phaleria macrocarpa (Scheff.) Boerl Extract in a Rat Iron Overload Model

Regular blood transfusions are typically used to treat the genetic anemia known as thalassemia, which can lead to an increase in the body's total iron levels. The condition of excess iron can be toxic to the body due to the formation of free radicals that are harmful and can damage cells and tissues. So the availability of free iron will form the basis of iron toxicity because it accelerates the Fenton reaction to produce an increase in the amount of ROS that cannot be suppressed so that saturation of the antioxidant system can occur. Excess iron has been known to be a risk factor for organ dysfunction and damage that results in various organ diseases such as liver, heart and kidney, diabetes mellitus, and neurodegenerative diseases. Mangiferin is an active compound has been shown to act as an iron chelating agent by forming complexes with iron. The complex formed can reduce iron accumulation in thalassemia patients who receive blood transfusions on a regular basis. Mahkota Dewa (Phaleria macrocarpa) is a well-known medicinal plant native to Papua, Indonesia, and it also includes the active ingredient mangiferin. This study aims to determine the effectiveness of the ethanolic extract of Phaleria macrocarpa fruit as an iron chelating agent observed in the kidneys in a rat model of excess iron

Study on the role of iron chelators in the management of iron overload among transfusion-dependent thalassemia (TDT) pediatric patients

This study aims to investigate the efficacy and safety of Deferasirox, an oral iron chelator, in reducing iron burden in pediatric patients with transfusion-dependent beta-thalassemia. Thalassemia syndromes, particularly beta-thalassemia, are inherited hemoglobin disorders requiring regular blood transfusions, leading to iron overload and subsequent complications. Effective management of iron overload is crucial to prevent morbidity and mortality. It was a descriptive observational study on Children between the ages of 2 years and 12 years who present with transfusion-dependent thalassemia and areon blood transfusion and develop iron overload, which is evaluated by serum ferritin levels of more than 2000mcg/l are administered iron chelator Deferasirox (14 mg/kg/d)and patients are evaluated for myocardial, hepatic, pancreatic iron burden and conditions of iron toxicity with the help of Cardiac MRI T2, LIC (Liver Iron Concentration), MRI T2 Pancreas, LVEF (Left Ventricular Ejection Fraction). A total of 22 patients enrolled in the study; significant reductions were observed in mean serum ferritin levels (2,388 mcg/dl to 2,054 mcg/dl, p=0.0009), transferrin saturation (70.45% to 64.32%, p=0.00005), and serum transaminases (44.55 U/L to 40.27 U/L, p=0.003) at 6 months. Cardiac MRI T2* increased from 19.55 ms to 22.95 ms (p=0.045) at the end of 6 months and at the end of 12 months from 19.55 to 28.23 (p=0.0016), and LIC reduced from 20.73 mg Fe/g dw to 11.59 mg Fe/g dw (p=0.00005). Pancreatic T2 improved from 15.96 ms to 20.23 ms at 12 months (p=0.007). A transient increase in serum creatinine was observed at 6 months from 0.64+/-0.14 mg/dL to 0.7+/-0.13mg/dL(p=0.009), which returned to normal at the end of 12 months to 0.63 mg/dL, no additional therapy-related adverse events were reported. Deferasirox has demonstrated significant efficacy in reducing iron overload in pediatric patients with transfusion-dependent beta thalassemia over a 12-month period. The substantial improvements in serum ferritin, cardiac MRI T2*, LIC, transferrin saturation, and pancreatic T2, coupled with its excellent safety profile, support the use of DFX as a cornerstone in the management of iron overload in this vulnerable population.

Correlation of Liver Enzymes and Serum Ferritin in Patients With β-Thalassaemia Major

Background: β-Thalassemia major is a hereditary hematological disorder that necessitates regular blood transfusions, leading to iron overload and subsequent liver injury. Elevated serum liver enzymes and ferritin are commonly used to monitor liver function in these patients; however, their reliability in predicting true hepatic dysfunction remains unclear. Objective: To determine the sensitivity, specificity, and diagnostic accuracy of serum liver enzymes and ferritin in predicting liver dysfunction, with hypoalbuminemia as the gold standard, in pediatric patients with β-thalassemia major. Methods: This cross-sectional validation study was conducted at the Department of Paediatrics, Combined Military Hospital, Rawalpindi, from July 2022 to February 2024. A total of 75 pediatric patients with β-thalassemia major were included using consecutive non-probability sampling. Patients with concurrent liver diseases, metabolic disorders, or conditions that could alter liver enzyme levels were excluded. Blood samples were collected to measure serum Alanine Transaminase (ALT), Aspartate Transaminase (AST), γ-Glutamyltransferase (γ-GT), ferritin, and albumin levels. Hypoalbuminemia was defined as a serum albumin level <3.5 g/L. The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ALT, AST, γ-GT, and ferritin in predicting hypoalbuminemia were calculated using 2×2 contingency tables. Data were analyzed using SPSS version 25. Results: Among the 75 patients, 18 (24.0%) exhibited hypoalbuminemia. The sensitivity, specificity, and diagnostic accuracy of ALT in detecting hypoalbuminemia were 83.33%, 31.58%, and 44.00%, respectively. For AST, these values were 50.00%, 29.82%, and 34.67%, respectively. γ-GT showed a sensitivity of 83.33%, specificity of 14.04%, and diagnostic accuracy of 30.67%. Ferritin had a sensitivity of 83.33%, specificity of 19.30%, and diagnostic accuracy of 34.67%. None of the markers showed satisfactory predictive value for hypoalbuminemia. There was a partial correlation between hyperferritinemia and elevated liver enzymes, with γ-GT showing the highest sensitivity (91.80%) and diagnostic accuracy (82.67%). Conclusion: Serum liver enzymes and ferritin are not reliable markers for predicting liver dysfunction as indicated by hypoalbuminemia in pediatric patients with β-thalassemia major. These findings suggest that additional clinical assessments and more specific biomarkers are necessary for accurate evaluation of liver health in this population.

The Diagnostic Performance of Serum Glycosylated Ferritin in Patients Undergoing Regular Blood Transfusion: An Indicator of Iron Overload to Initiate Iron Chelation Therapy.

Background and objective Serum ferritin concentration and transferrin saturation are commonly employed to estimate body iron but are non-specific to iron overload. Glycosylated ferritin may be primarily elevated in cases of iron overload in patients undergoing regular blood transfusions. In this study, we aimed to estimate glycosylated ferritin and determine its cutoff values for iron overload in patients receiving blood transfusions regularly. We also endeavored to the examine correlation between serum ferritin and glycosylated ferritin in patients receiving regular blood transfusions. Methods We conducted a cross-sectional study involving 17 patients undergoing regular blood transfusions in the Department of Medical Oncology/Hematology, who had already received ≥10 transfusions without any iron chelation therapy or acute inflammation. All participants were evaluated based on a questionnaire to gather relevant medical details. Serum iron, ferritin, glycosylated ferritin, and unsaturated iron-binding capacity (UIBC) were estimated. Total iron-binding capacity (TIBC) and transferrin saturation were also calculated. Results Participants were divided into two groups based on transferrin saturation (≥50% as a reference for iron overload). The group with transferrin saturation ≥50% had significantly higher levels of serum ferritin, glycosylated ferritin, and iron, compared to the group with transferrin saturation <50%. Glycosylated ferritin showed a positive correlation with ferritin (rho=0.80) and transferrin saturation (rho=0.64), which was statistically significant. UIBCand TIBCshowed a negative association with glycosylated ferritin. The correlation of glycosylated ferritin with units of blood transfusion (Spearman's rho=0.60) was found to be better than that of serum ferritin (Spearman's rho=0.52). Conclusions Based on our findings, glycosylated ferritin could be a potential marker for transfusion-related iron overload. The optimal cutoff value for iron overload using serum glycosylated ferritin level was >587.55 ng/mL. Further extensive studies withlarger sample sizes will substantiate the role of glycosylated ferritin in predicting post-transfusion iron overload.

Analysis of Thalassemia Gene Mutation Types and Ethnic Distribution Characteristics in Hechi Area, Guangxi

To investigate the genotype, mutation type, and ethnic distribution characteristics of thalassemia in the population of Hechi area, Guangxi, and to provide a reference basis for prevention and control of thalassemia and eugenic counseling in the region. Gap-polymerase chain reaction (gap-PCR) and reverse dot blot (RDB) were used for genetic testing on suspected thalassemia persons, and the results were analyzed. Among 29 136 samples, a total of 17 016 (58.40%) positive samples for thalassemia genes were detected, with a higher detection rate in males than in females (χ2=49.917，P < 0.001). The detection rates of thalassemia genes were significant different among Zhuang, Han, Yao, Mulao, and Maonan ethnic groups (χ2=546.121, P < 0.001). The α-thalassemia genotypes were mainly --SEA /αα (16.67%), -α3.7/αα (8.90%), α CSα/αα (6.00%). Additionally, four rare genotypes were detected, including -- THAI/αα (47 cases), HKαα/αα (2 cases), --SEA /-α 21.9 (2 cases), and -- THAI/αCSα (1 case). The β-thalassemia genotypes were mainly β CD17/βN (7.49%), βCD41-42/βN (6.70%), βCD71-72/βN (0.44%). 108 cases of moderate and severe β-thalassemia were detected, of which 81 cases had a history of blood transfusion, the transfusion frequency of 60 cases was more than 10 times/year, and 10 cases received bone marrow transplantation. Thalassemia in Hechi area is predominantly deletion type --SEA /αα, the detection rate of thalassemia in ethnic minorities is higher than that in Han population. In this area, moderate and severe β-thalassemia have certain incidence, these patients mostly need regular blood transfusion and iron removal treatment, and very few patients have received bone marrow transplantation. This study provides a certain reference basis for prevention and control of thalassemia and eugenic counseling in the region.

STUDY OF THE LONG-TERM EFFECTS OF DIABETES ON THE OVERALL HEALTH AND QUALITY OF LIFE IN THALASSEMIA PATIENTS

Thalassemia is a genetic blood disorder characterized by chronic anemia, requiring regular blood transfusions and chelation therapy. Diabetes mellitus is a common complication in thalassemia patients, primarily due to iron overload affecting the pancreas. This study investigates the long-term effects of diabetes on the overall health and quality of life in thalassemia patients. The research aims to understand how diabetes exacerbates complications associated with thalassemia and to identify strategies for improved management and care. The study includes a cohort of thalassemia patients with diabetes, compared to a control group of thalassemia patients without diabetes. Parameters assessed include glycemic control, incidence of diabetes-related complications, and overall health markers such as liver function, cardiovascular health, and renal function. Quality of life is measured using standardized questionnaires addressing physical, emotional, and social well-being. Preliminary findings indicate that thalassemia patients with diabetes have a significantly higher incidence of comorbid conditions, including cardiovascular disease and renal impairment (De Sanctis et al., 2016). Additionally, the quality of life in these patients is notably lower, with increased reports of fatigue, pain, and psychological distress (Haines et al., 2013). Effective management of diabetes in thalassemia patients, through regular monitoring and tailored treatment plans, is crucial in mitigating these adverse effects and improving patient outcomes (Farmaki et al., 2006). This study underscores the importance of integrated care approaches for thalassemia patients with diabetes, emphasizing the need for multidisciplinary teams to address the complex interplay of these conditions. Further research is needed to develop targeted interventions that can enhance the long-term health and quality of life for this vulnerable patient population. Results: study indicated that plant extracts exhibited higher inhibition than antibiotics. The minimum inhibitory concentration (MIC) while the results of the lowest inhibitory concentration of carvacrol for the bacterial species under study showed that it had an effect at a concentration of 615 µg/ml against Escherichia coli, 307.5 µg/ml for the species Corynebacterium stratium, Morganella morganii and Pseudomonas aeruginosa, and the least effect was 76.875 µg/ml on Staphylococcus aureus, it gave less results than the antibiotic used Carvacrol (Absorbance was measured at Wavelength 600) .

A novel PEG-mediated approach to entrap hemoglobin (Hb) within ZIF-8 nanoparticles: Balancing crystalline structure, Hb content and functionality

Hemoglobin (Hb)-based oxygen carriers are investigated as a potential alternative or supplement to regular blood transfusions, particularly in critical and life-threatening scenarios. These include situations like severe trauma in remote areas, battlefield conditions, instances where blood transfusion is not feasible due to compatibility concerns, or when patients decline transfusions based on religious beliefs.This study introduces a novel method utilizing poly(ethylene glycol) (PEG) to entrap Hb within ZIF-8 nanoparticles (i.e., Hb@ZIF-8 NPs). Through meticulous screening, we achieved Hb@ZIF-8 NPs with a record-high Hb concentration of 34 mg mL−1. These NPs, sized at 168 nm, displayed exceptional properties: a remarkable 95 % oxyhemoglobin content, excellent encapsulation efficiency of 85 %, and resistance to Hb oxidation into methemoglobin (metHb). The addition of PEG emerged as a crucial factor amplifying Hb entrapment within ZIF-8, especially at higher Hb concentrations, reaching an unprecedented 34 mg mL−1. Importantly, PEG exhibited a protective effect, preventing metHb conversion in Hb@ZIF-8 NPs at elevated Hb concentrations.

Immunophenotypic Evaluation of Circulating Monocyte Subsets in Beta Thalassemia Major Patients

Abstract Background β-thalassemia is a major public health problem in Egypt with particularly high incidence due to strong cultural preference for consanguineous marriages, and the high carrier rate. Iron overload, which is caused by increased gut iron absorption secondary to ineffective erythropoiesis, and regular blood transfusion is linked to accumulation within different organs with subsequent organ dysfunction. Monocytes are important lineages of innate immunity which activate the adaptive immune response and play a pivotal role in the host response to pathogens. Human blood monocyte subsets classification is based on the expression of CD14 and CD16 cell surface receptors. Aim of the Work To evaluate the circulating monocyte subsets in β-thalassemia major (β-TM) patients and its potential role in prediction of iron overload and chronic inflammation in β- thalassemia major patients. Patients and Methods A Case-Control study conducted on 40 previously diagnosed beta thalassemia major patients attending the outpatient clinic of Ain Shams University Pediatric Hospital, and 20 age and sex matched healthy control subjects. CBC, iron profile, CRP and immunophenotyping for monocyte subsets classification were done. Results Non classical monocytes were found statistically significantly higher in thalassemic patients especially in those with serum ferritin level &amp;lt; 1000 ng/ml (P value &amp;lt; 0.01). In addition, classical monocytes were found to be statistically significantly lower among the patients’ group (P value &amp;lt; 0.01). A negative correlation was found between intermediate monocytes and Transferrin saturation percent (TS%) suggesting its protective role in iron overload thalassemia patients. By using ROC curve, non- classical monocytes predicted ferritin &amp;lt; 1000 ng/ml at a cutoff point of 17.8 % and 0.05 x 10∧9/L for relative and absolute counts respectively. Conclusion All monocyte subsets proposed to have role in predicting iron overload and chronic inflammation β-TM patients. We recommend further studies on β-TM patients with the engagement of activity assays of monocyte subsets to clarify the co-regulatory role in iron hemostasis and chronic inflammation.

Correlation between Serum Ferritin and Thyroid Hormones Level in Children with Thalassemia

Background: Thalassemia is a group of hereditary blood disorder characterized by reduced or absent globin chain synthesis resulting in transfusion dependent anaemia and iron overload. Due to regular blood transfusion and inadequate chelation therapy patient develop multiorgan dysfunction. Objectives: To find any correlation between serum ferritin and thyroid hormones level in children with transfusion dependent thalassemia. Methods: This cross-sectional study was carried out in the department of Paediatrics and department of Medicine, Sylhet MAG Osmani Medical College Hospital between June, 2021 to May, 2022, on one hundred children with transfusion dependent thalassemia who were on more than 12 times blood transfusion but did not take any chelation therapy and whose serum ferritin level were &gt; 1000 ng/ml. Assessment of their thyroid hormones level and statistically its correlation with serum ferritin were done. Result: A total of 53 (53%) male and 47 (47%) female were included in this study. The mean age of the patients was 9.47 ±3.63 years. Mean serum ferritin was 1980±1126.19 ng/ml, mean serum TSH was 3.55±2.08 µIU/ml, mean serum free T4 was 1.10±0.18 ng/ml, mean serum free T3 was 3.64±0.37 pg/ml. Subclinical hypothyroidism and euthyroid were found in 20 patients (20%) and 80 patients (80%) respectively. No overt hypothyroidism or hyperthyroidism were found. Mean serum ferritin in subclinical hypothyroid and euthyroid were 2407±995.37 ng/ml and 1875.59±1131.18 ng/ml respectively which difference was statistically significant (P value &lt;0.05). Scattered diagram was done and it showed linear correlation between serum ferritin and serum TSH of subclinical hypothyroid group. No linear correlation was found between serum ferritin and F.T3 and F.T4 on scattered diagram. Positive (Pearson) correlation was found between serum ferritin and serum TSH of subclinical hypothyroid group and strong positive (Pearson) correlation (r=0.74, P=0.02) was found between them. Conclusion: This study showed that good percentages of children with transfusion dependent thalassemia are suffering from subclinical hypothyroidism. There is positive correlation between serum ferritin level and subclinical hypothyroidism.

#2308 The effect of Dapagliflozin on albuminuria and biomarkers associated with renal function in patients with β-thalassemia and/or sickle-cell disease

Abstract Background and Aims Patients with β-thalassemia present already from the 1st year of life with serious anemia thus needing regular blood transfusions in order to attain normal hemoglobin levels. Chronic anemia, iron overload and the use of iron chelating agents have been associated with renal dysfunction. In sickle-cell syndromes, which include sickle-cell anemia and sickle-cell trait, patients present with typical kidney functional and structural defects, resulting in urinary concentrating defects, distal nephron dysfunction and albuminuria. Sodium–glucose cotransporter-2 inhibitors (SGLT-2i) have shown beneficial effects on renal outcomes in large clinical trials with the added benefit of a substantial decrease in albuminuria. The aim of this prospective, non randomized open label study is to investigate the effect of Dapagliflozin at a dose of 10 mg daily on albuminuria and the overall progression of CKD in patients with β-thalassemia and/or sickle-cell disease undergoing regular blood transfusions. Method In this study we included adult patients undergoing regular blood transfusions with a baseline albuminuria of ACR&amp;gt;30 mg/gCr (assessed with a spot urine sample) who received treatment with Dapagliflozin, a second group with no albuminuria that did not receive treatment and a group of adults with no kidney disease (Controls). In all patients renal function biomarkers were measured in urine and serum with commercial ELISA kits (NGAL and uPAR in serum, MMP9 and KIM-1 in urine), while in patients that received Dapagliflozin additional measurements of ACR and eGFR (CKD-EPI formula) were performed after 3 months of treatment initiation. Results In this study we included 16 patients (7 males) with β-thalassemia and/or sickle-cell disease with ACR&amp;gt;30 mg/gCr, 35 patients (17 males) with β-thalassemia and/or sickle-cell disease without albuminuria and 20 controls (13 males). Patients that received Dapagliflozin showed a significant reduction in albuminuria three months post-initiation of treatment (ACR: 0.52 ± 1.2 vs. 0.3 ± 0.68 mg/g, p=0.006) while kidney function showed a slight non-significant reduction (eGFR: 99.3 ± 21.7 vs. 94.7 ± 28.9 ml/min/1.73m2, p=0.36). Concerning the urine and serum biomarkers of tubular dysfunction, inflammation and kidney disease progression, all were significantly increased in patients with β-thalassemia and/or sickle-cell disease in comparison to controls (Table 1). In patients that received treatment with Dapagliflozin, NGAL, MMP-9 and suPAR at 3 months post-treatment initiation did not show any significant reduction (Table 2). Conclusion Patients with β-thalassemia and/or sickle-cell disease show increased urine and serum levels of kidney damage biomarkers in comparison to healthy controls. Treatment of these patients with Dapagliflozin for 3 months has a significant effect in albuminuria reduction while it does not alter urine and serum levels of these biomarkers.

Serum Zinc and Copper Levels in Children with Thalassemia Major

Background: Thalassemia is a frequent hereditary genetic with different clinical manifestations from mild to severe based on its genetic. Beta thalassemia major is the worse form of this disease caused by decreased or absent beta globin chains of hemoglobin. Regular blood transfusion is the main aim leads to iron overload and deposition of iron in different organs.Objectives: To determine different serum distribution levels and correlation of copper and zinc in transfusion dependent thalassemia patients Material and Methods: This was a descriptive cross-sectional study in which a non-probability convenient sampling technique was used for sample collection. This study was conducted in KPK in a total of 137 patients, who were diagnosed cases of thalassemia major by hemoglobin electrophoresis, enzyme linked immunosorbent assay (ELISA) method and receiving iron and folate therapy. SPSS version 22 was used and Pearson's correlation coefficient was applied. P-value 0.05 was considered significant.Results: In this study mean age was 6.7±3.49 years. 77 (56%) percent children were male while 64 (44%) children were female. Mean hemoglobin (Hb) level was 7.43±1.3 gm/dl. Mean SGPT score was 26.28 ± 7.51. Mean blood urea was 21.10 ± 8.49 mmol/l while mean serum creatinine level was 0.56 ± 0.26 mg/dl. Mean serum zinc level was 13.36 ± 11.12mg/dl while mean serum copper level was 1.21± 0.60 mg/dl and mean serum ferritin level was 6682 ± 533 Ug/l.Conclusion: This study showed hypozincemia in thalassemia major patients, but copper deficit was not present. There was no substantial variance between serum ferritin level and mean serum concentration of zinc and copper in this study. Ancillary assessments in this respect is recommended. Keywords: Copper, Thalassemia, Zinc

Analysis of Plasma Metabolic Profile in Children with Transfusion-Dependent Thalassemia

To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia (TDT), and reveal the changes of metabolic pattern in children with TDT. 23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected, and 11 healthy children who underwent physical examination during the same period were selected as the control group. The routine indexes between children with TDT and the control group were compared, and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry. An OPLS-DA model was established to perform differential analysis on the detected metabolites, and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites. The results of routine testing showed that the indexes of ferritin, bilirubin, total bile acid, glucose and triglycerides in children with TDT were significantly higher than those in healthy controls, while hemoglobin and total cholesterol were significantly lower (all P <0.05). However there was no significant difference in lactate dehydrogenase between the two groups (P >0.05). Compared with the control group, 190 differential metabolites (VIP>1) were identified in TDT children. Among them, 168 compounds such as arginine, proline and glycocholic acid were significantly increased, while the other 22 compounds such as myristic acid, eleostearic acid, palmitic acid and linoleic acid were significantly decreased. The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism. The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group. This finding is helpful to optimize the treatment choice for children with TDT, and provides a new idea for clinical treatment.

Study of Alloimmunization in Transfusion-dependent Thalassemia Patients at a Tertiary Care Hospital

Abstract: BACKGROUND: Alloantibodies against donor red blood cells (RBCs) are developed by patients with transfusion-dependent thalassemia (TDT), which causes the donor RBCs to hemolyze. This decreases the transfusion’s efficacy and increases the risk of adverse effects like iron overload. MATERIALS AND METHODS: Two hundred and five TDT patients with an average age of 11 ± 6 years enrolled in this study underwent the Direct Coombs Test (DCT) to determine the frequency of alloimmunization. RESULTS: Most cases were of thalassemia major (TM) (76.09%), followed by thalassemia intermedia (TI) and (21.95%). Most of the cases were diagnosed and started on regular blood transfusion therapy between the ages of 1 and 10 years. Majority of the cases were born of parental consanguinity. Only 13.17% of the patients underwent splenectomy, of which TM cases were the majority. Even though O-positive was the most frequent blood type, most of the operated and alloimmunized cases belonged to the B-positive blood type. Only 10.24% of the patients had alloimmunization, with 51.85% of them developing it after splenectomy. Among all study participants, no correlation was found between the blood group and the type of thalassemia, alloimmunization, or splenectomy. Among TDT cases, there was a significant correlation (P &lt; 0.0001) between alloimmunization and splenectomy. Alloimmunization and splenectomy correlated significantly with the total number of transfusions, the volume of blood transfused, and the transfusion initiation age. CONCLUSION: Our findings emphasize the significance of antigen typing in TDT patients before the first transfusion.