Thalassemia Patients Research Articles

Prediction the Occurrence of Thalassemia With Hematological Phenotype by Diagnosis of Abnormal HbA1c.

The current investigation aims to analyze the occurrence of thalassemia in patients who participated in hemoglobin A1c (HbA1c) testing in clinical laboratory showing high hemoglobin F (HbF) level (≥ 1.5%) or abnormal Hb peak and predict the main influence factors by using different statistical models. The current investigation is a single-center retrospective cohort study. HbA1c concentration was detected by using TOSOH HLC-723G8 glycated hemoglobin analyzer. SNaPshot SNP (Single Nucleotide Polymorphism) typing and AccuCopy technology were employed to detect mutations in thalassemia-related pathogenic genes. A total of 126 patients endured high HbF levels or abnormal Hb peak during HbA1c detection, and 66.7% of subjects (n = 84) showed thalassemia mutations. Three heterozygosity mutations, including c.52A>T (p.K18*), c.-78A>G, and c.126_129delCTTT(p.F42Lfs*19) present in HBB gene, were also identified. --SEA/αα mutation demonstrated the youngest ages (p < 0.001). 17 M (p < 0.001) and 41/42 M (p < 0.01) mutations with β-thalassemia showed higher HbF levels compared with patients without thalassemia mutations. Except for -α3.7, mutations in thalassemia showed lower levels of mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) compared with patients without thalassemia mutations. Patients with thalassemia mutations showed younger age (p < 0.001), lower Hb (p < 0.001), MCV and MCH levels (p < 0.001), higher red blood cell (RBC)count (p < 0.001), and platelet distribution width (PDW) level (p = 0.007) than patients without thalassemia mutations. Three statistical models indicate MCV is the most valuable independent factor for predicting thalassemia and ROC (receiver operating characteristic) curves analysis of AUC (Area Under the Curve) of 0.855 (95% CI [0.787-0.923], p < 0.001) with MCV. High HbF level (≥ 1.5%) or abnormal Hb peak present in HbA1c testing indicated high incident rate of thalassemia. MCV is the most valuable independent predicting factor for subjects having thalassemia.

A Survey of Acute Transfusion Reactions in Thalassemic Patients in Pakistan: A Single Centre Experience

Background: Blood transfusion reactions are characterized as adverse reactions linked to whole blood or any of its constituent parts, encompassing a spectrum of severity levels, from minor to potentially life-threatening. The administration of blood products is a common practice to enhance the hemodynamic status and overall clinical well-being of patients. However, it's important to note that transfusing blood components comes with potential complications, both infectious and non-infectious in nature. Objective: The current study aim to evaluate the type and frequency of transfusion reactions in thalassemic patients at Hamza Foundation Welfare Hospital and Blood Services, Peshawar. Method: The current study was a descriptive cross-sectional study. The data was collected from 152 participants through a self-generated questionnaire during the 4 months (from April to July 2022) study period. Results: The overall frequency of febrile non-hemolytic reactions (FNHTR), allergic transfusion reactions (ATR), and acute hemolytic transfusion reactions (AHTR) was 84%. Among the 152 participants, 91 (59.8%) were males, and 61 (40.2%) were females. Of the total males, 83 (55.6%) experienced transfusion reactions, while 46 (30%) of the females had transfusion reactions. Specifically, 56 males and 36 females experienced FNHTRs, 22 males and 4 females experienced ATRs, and 5 males and 6 females experienced AHTRs. Fever was observed predominant symptom 69.7% and 52.6% among FNHTR and AHTR, anxiety was predominantly observed in 34.8% in ATRs. Conclusion: Among the transfusion reaction types, FNHTRs emerged as the most common, followed by ATRs and AHTRs. Key words: Febrile Non-Hemolytic Reaction, Allergic Transfusion Reaction, Hemolytic Transfusion Reactions

Vamifeport: Monography of the First Oral Ferroportin Inhibitor.

Over the last few years, several mechanisms that are involved in congenital diseases characterized by ineffective erythropoiesis have been described. Therefore, multiple new target drugs are being developed in preclinical models against the main regulators of normal erythropoiesis. Above all, the key mechanism that regulates systemic iron homeostasis, represented by the hepcidin-ferroportin axis, is considered to be the target for new therapies. The main hypothesis is that iron restriction, through blocking ferroportin (the unique iron transporter in mammals) in such diseases, ameliorates erythropoiesis. The action of vamifeport is different from the currently approved drugs in this setting since it acts straight on the ferroportin-hepcidin axis. The data presented in the sickle cell disease (SCD) Townes mouse model showed a preclinical proof-of-concept for the efficacy of oral ferroportin inhibitor. Vamifeport reduced hemoglobin concentration in red blood cells (RBCs) and diminished intravascular hemolysis and inflammation, improving hemodynamics and preventing vascular occlusive crises. On this basis, clinical trials were commenced in patients with SCD, non-transfusion-dependent (NTD) thalassemia and transfusion-dependent (TD) thalassemia. Preliminary data in NTD thalassemic patients also confirm the safety and efficacy in decreasing iron level. In conclusion, vamifeport represents a new option in the panorama of drugs targeting the hepcidin-ferroportin axis, but its efficacy is still under investigation as a single agent.

Assessment of Cardiac, Hepatic and Pancreatic Iron Overload in Transfusion Dependent Thalassemia Patients Using T2* Magnetic Resonance Imaging

Assessment of Cardiac, Hepatic and Pancreatic Iron Overload in Transfusion Dependent Thalassemia Patients Using T2* Magnetic Resonance Imaging

Renal Findings in Patients with Thalassemia at Abdominal Ultrasound: Should We Still Talk about "Incidentalomas"? Results of a Long-Term Follow-Up.

We retrospectively collected all ultrasound imaging data of our thalassemia patients over a period of 10 years with the aim of assessing the prevalence and the risk factors of renal stones and cysts. Moreover, we assessed the incidence of renal-cell carcinoma (RCC) among thalassemia patients (133 with thalassemia major (TM) and 157 with thalassemia intermedia (TI)) and its association with demographic and clinical findings. Renal stones were detected in 15.2% of patients. In the multivariable Cox regression analysis, the independent predictors were blood consumption, splenectomy, and proteinuria. Renal cysts were detected in 18.4% of patients. In the multivariable analysis, age emerged as the only independent predictor. After the first detection, 35% of the patients showed changes in the number, size, or grading of renal cysts. During the study period, the crude incidence rate of RCC was 75.9 cases per 100,000 person-years. The most frequent histological subtype (80%) included clear-cell RCC. In total, 80% of patients with RCC had TM and all were positive for hepatitis C virus antibodies. Thalassemia patients are significantly affected by asymptomatic renal diseases such as stones, cysts, and cancer, suggesting the need for regular screening by imaging.

Levels of IL-18 and IL-28 in thalassemia patients with viral infections

Thalassemia is an inherited hemoglobin disorder that requires lifelong medical care. Patients with thalassemia are very prone to infections by viruses, which may exacerbate their condition, leading to serious complications. Knowledge of the immune response in these patients could be very helpful in the effective management of their disease. The levels of IL-18 and IL-28 were evaluated in thalassemia patients with different viral infections to assess their potential as biomarkers and therapeutic targets. This was a retrospective analysis of clinical data on thalassemia patients with viral infections. Demographic, clinical, laboratory, IL-18, and IL-28 data at baseline were included in the study. In the present study, the authors assessed the correlations between interleukin levels, viral infection, treatment response, and overall survival. The study enrolled 250 patients with thalassemia and different viral infections. In these patients, the levels of IL-18 and IL-28 were found to be elevated with a significant correlation to viral load. Thus, a higher baseline interleukin level predicted a better treatment response and overall survival. Elevations in IL-18 and IL-28 in thalassemia patients with associated viral infections likely indicate immune system activation. Their correlation with viral load and treatment outcomes suggests their potential as biomarkers and targets for therapy. These findings further underline the protective role of IL-18 and IL-28, hence contributing to enhanced survival rates of the patients. Further studies for translation of these insights into practice may help modify clinical care for better patient outcomes.

Through the Eyes of the Recipient: Navigating Transfusion Services Amidst COVID-19 in Multi-Transfused Thalassaemic Patients

Through the Eyes of the Recipient: Navigating Transfusion Services Amidst COVID-19 in Multi-Transfused Thalassaemic Patients

SNPscan Combined With CNVplex as a High-Performance Diagnostic Method for Thalassemia.

Thalassemia is a Mendelian-inherited blood disorder with severe consequences, including disability and mortality, making it a significant public health concern. Therefore, there is an urgent need for precise diagnostic technologies. We introduce two innovative diagnostic techniques for thalassemia, SNPscan and CNVplex, designed to enhance molecular diagnostics of thalassemia. The SNPscan and CNVplex assays utilize variations in PCR product length and fluorescence to identify multiple mutations. In the SNPscan method, we designed three probes per locus: two 5' and one 3', and incorporated allele identification link sequences into one of the 5' probes to distinguish the alleles. The detection system was designed for 67 previously reported loci in the Chinese population for a specific genetic condition. CNVplex identifies deletion types by analyzing the specific positions of probes within the globin gene. This innovative approach enables the detection of six distinct deletional mutations, enhancing the precision of thalassemia diagnostics. We evaluated and refined the methodologies in a training cohort of 100 individuals with confirmed HBA and HBB genotypes. The validation cohort, consisting of 1647 thalassemia patients and 100 healthy controls, underwent a double-blind study. Traditional diagnostic techniques served as the control methods. In the training set of 100 samples, 10 mutations (Hb QS, Hb CS, Hb Westmead, CD17, CD26, CD41-42, IVS-II-654, --SEA, -α3.7 and -α4.2) were identified, consistent with those identified by traditional methods. The validation study showed that SNPscan/CNVplex offered superior molecular diagnostic capabilities for thalassemia, with 100% accuracy compared to 99.43% for traditional methods. Notably, the assay identified three previously undetected mutations in 10 cases, including two deletion mutations (Chinese Gγ(Aγδβ)0 del and SEA-HPFH), and one non-deletion mutation (Hb Q-Thailand). The SNPscan/CNVplex assay is a cost-effective and user-friendly tool for diagnosing thalassemia, demonstrating high accuracy and reliability, and showing great potential as a primary diagnostic method in clinical practice.

Study of platelet activation, hypercoagulable state, and pulmonary hypertension in patients with transfusion-dependent beta-thalassemia

Abstract: BACKGROUND: Thalassemic patients require lifelong blood transfusions, which can lead to complications such as pulmonary arterial hypertension. The pathogenesis involves hypercoagulability, in which researches on coagulation abnormalities in this regard are limited. OBJECTIVES: The aims of the study was to investigate the mechanism of hypercoagulability and pulmonary hypertension in transfusion-dependent thalassemic patients and compare it with healthy controls. PATIENTS MATERIALS AND METHODS: This case–control analysis enrolled 50 transfusion-dependent thalassemia patients and 50 healthy controls. Complete blood counts, liver function tests, coagulation markers (P-selectin, protein C, antithrombin III, and fibrinogen), serum ferritin, and transthoracic echocardiography were performed, and blood transfusion/chelation history and splenectomy status were recorded. RESULTS: Thalassemia patients revealed severe anemia, leukocytosis, thrombocytosis, significantly elevated serum ferritin (1957.50 ± 2455.05 g/L), elevated liver enzymes serum glutamic oxaloacetic transaminase (22.01 ± 9.89 U/L), serum glutamic pyruvic transaminase (22.70 ± 9.78 U/L) in comparison to controls, and mean serum P-selectin was significantly higher in thalassemic patients (100.48 ± 53.29 ng/mL). Mean serum antithrombin-III and protein C were significantly lower in thalassemic patients (89.27 ± 16.08 units/h, 86.04 ± 25.21 μg/mL) in comparison to controls. CONCLUSIONS: Transfusion-dependent thalassemia is characterized by severe anemia and splenomegaly, leading to complex hemodynamic changes with evidence of platelet activation, hypercoagulable state, liver injury, and increased atherosclerosis. It induces pulmonary artery thrombosis contributing to the development of pulmonary artery hypertension.

Quantifying non-transferrin-bound iron (NTBI) in human plasma: incorporating BODIPY-pyridylhydrazone (BODIPY-PH) within a thin green film linked to a portable fluorescence-based device.

Free iron in human serum or non-transferrin-bound iron (NTBI) can generate free radicals and lead to oxidative damage. Moreover, it is highly toxic to various tissues and a vital biomarker related to the iron-loading status of thalassemia and Alzheimer's patients. In NTBI in healthy individuals, NTBI levels are typically less than 1µM; current NTBI analysis usually requires advanced instrumentation and many-step sample pretreatment. To address this issue, we employed our invented BODIPY derivative, BODIPY-PH, as a fluorescence probe and trapped it onto the microcentrifuge tube lid using tapioca starch. The fluorescence intensity of BODIPY-PH increased with increasing NTBI concentration (turn-on). The developed portable reaction chamber facilitates rapid analysis (∼5min) using small sample volumes (10 μL sample in a total volume of 600 μL). Under optimum conditions, using the sample-developed portable fluorescence device and fluorescence spectrometer, we achieved impressive limits of detection (LOD) of 0.003 and 0.0015μM, respectively. Furthermore, the developed sensors show relatively high selectivity toward Fe3+ over other metal ions and biomolecules (i.e., Fe2+, Cr3+, Cu2+, and glucose). The sensor performance in serum samples of thalassemia patients exhibited no significant difference compared to the labeled value (obtained from standard methods). Overall, the developed fluorescence sensor is suitable for determining NTBI and offers high sensitivity, high selectivity, and a short incubation time (5min). Moreover, the method requires a limited number of reagents, is simple to use, and uses low-cost equipment to determine NTBI in human serum samples.

Assessment of the vitamin D level and demographic characteristics of children suffering from β-thalassemia in Thi-Qar province

Beta thalassemia is a genetic disorder inherited by autosomal recessive inheritance, is present all over the world . Lifelong transfusions are necessary for people with beta-thalassemia, which can result in an iron buildup in the skin, liver, and kidneys that reduces the production of vitamin D. This study aims to evaluate vitamin D levels, blood groups, and demographic characteristics in beta-thalassemia patients. The current study was conducted at the thalassemia center and hereditary blood disease in Thi-Qar Province with eighty-eight blood samples collected from individuals. It was divided into three groups according to age range, the first group (2-6), the second group (7- 11), and the third group (12- 15). In the current study, there was a significant decrease in Vit-D3 levels among thalassemia patients compared to the control group (p ≤ 0.05) . As for age between the patients group and the control group, the highest proportion of patients in the third age group. As for gender, the results of the study found a non-significant difference at the (P ≤ 0.05 ) level between the patients group and the control group. The most common blood group in thalassemia was O followed by blood groups A, B, and AB. It also shows that the majority of the population was positive Rh.

Role of Quercetin Supplementation on Iron Parameters in Blood Transfusion-Dependent Thalassemia Patients

Background: Thalassemia is a group of inherited blood disorders that affect the production of hemoglobin, a protein in red blood cells that carries oxygen throughout the body. Iron overload is a condition in which the body absorbs and stores too much iron. In addition to repeated blood transfusions, increased gastrointestinal tract (GIT) iron absorption plays an important role in iron overload with thalassemia. Quercetin, a common flavonoid present in fruits and vegetables, exhibits diverse biological effects. Objective: To assess the effect of quercetin on iron overload parameters in blood transfusion-dependent thalassemia patients (TDT). Methods: A randomized, double-blind, placebo-placebo group-led study was conducted on 110 TDT patients, more than 12 years of age, who were supplemented with either quercetin or a placebo capsule daily (500 mg) for 3 months. A blood sample was obtained for laboratory parameters at baseline and at the end of 3 months. Results: At the baseline time of the study, the demographic features and iron overload parameters of patients and the placebo group were not statistically different, while after three months of supplementation, there was a significant decrease in levels of serum iron, UIBC, serum ferritin and ferritin saturation rate, and a significant increase in TIBC in the patients compared with the placebo group. Conclusions: The study shows the significant role of quercetin on iron overload parameters in blood transfusion-dependent thalassemia patients.

The Effect of Parental Support on the Quality of Life of Children with Thalassemia

Introduction: Thalassaemia is a blood disorder that is passed down from parents to their children. Patients should receive blood transfusions regularly. Children with thalassaemia will undergo treatment for a long time. These extreme impacts cause various physical, emotional, social, and environmental disorders that can reduce the quality of life of people with persistent thalassaemia major. Objectives: This study aims to determine the effect of family support on the quality of life in children with thalassaemia major. Methods: This research is a type of quantitative correlation with the cross-sectional approach. The sample of all thalassemia patients in April-August 2022 until 2024 Agustus, was 120 pediatric patients selected using the total sampling technique. Bivariate analysis using chi square. Results: The age characteristics of children with thalassaemia were 83 (69.2%), the majority of females were 65 (54.2%). Family support was mostly positive for 63 (52.5%) and the quality of life of children with thalassaemia was mostly for 64 respondents (65.8%) in the normal category. There is a relationship of family support for the quality of life of children with thalassaemia at the Dr. Soedirman Regional General Hospital, Kebumen. Conclusions: Support family and friends, as well as providing a adequate for parents is very important in improving the quality of life of children Thalassaemia.

Genotype Distribution and Clinical Characteristics of Thalassemia Patients Needing Transfusion in Yangjiang, Western Guangdong

Plain Language SummaryThis study is a retrospective research that investigates the genotype distribution and iron metabolic imbalance in thalassemia patients requiring blood transfusion. Eighty-four thalassemia patients needing transfusion were enrolled in the study and underwent genotype analysis. Among these patients, 56 were transfusion-dependent and 28 were non-transfusion-dependent. Of the 56 transfusion-dependent patients, 48 were observed for 3 years, and their iron overload status was analyzed in this study. Our research found that among the 84 thalassemia patients needing transfusion, there were six types of α-thalassemia deletions and nine types of β-thalassemia mutations. Among the 56 transfusion-dependent patients, three types of α-thalassemia genotypes and 15 types of β-thalassemia genotypes were identified. Among the 48 transfusion-dependent thalassemia patients observed for 3 years, 40 patients exhibited iron overload with SF levels exceeding 1,000 ng/mL. The recent SF levels were lower than those 3 years ago. Our study found that β-thalassemia is the most common type of transfusion-dependent thalassemia. Standard blood transfusion and iron chelation therapy are necessary for transfusion-dependent thalassemia patients. While some patients show a reduction in SF levels after 3 years of treatment, there are still individuals who exhibit elevated levels necessitating ongoing management.

Exploring Perceptions of Marriage and Reproductive Health Among Thalassemia Patients in Banyumas Regency

Exploring Perceptions of Marriage and Reproductive Health Among Thalassemia Patients in Banyumas Regency

Oropharyngeal Cancer in a Thalassemic Patient: Role of Iron Overload in Carcinogenesis

ABSTRACT The thalassemia syndromes are inherited α and β globin biosynthesis disorders. Patients with β thalassemia major require intensive blood transfusions to survive. Chronic blood transfusions can lead to blood-borne infections, alloimmunization, febrile reactions, and lethal iron overload. With the recent advances in treatment approaches and improvements in chelation therapy, thalassemic patients are living longer. Because of this, new complications are emerging, the majority of which are related to the treatment, and few are related to the primary pathology. One of the rarely reported complications is malignancy. The role of iron in carcinogenesis is still debatable. The role of iron in colorectal, liver, kidney, lung, and stomach cancer either as a cancer initiator or as a promoter is well documented. The most probable causes are iron autooxidation, pro-inflammatory cytokines activation of oxidative responsive transcription factors, and iron-induced hypoxia signaling. However, there is hardly any literature mentioning the role of iron in head-and-neck cancers. We report a case of oropharyngeal cancer in a thalassemia patient and discuss the possibility of association between the two diseases with emphasis on the aggressiveness of the cancer in the background of thalassemia and iron overload.

The burden of thalassemia disorder: Past and present: The feedback of patients experience in the COVID-19 pandemic crisis

Abstract: Thalassemia is a genetic blood condition and one of the emerging global public health concerns in the world, with an estimated prevalence of 300,000,000 . The genes controlling hemoglobin production are affected, leading to an anemia of variable severity. Carriers of this hereditary anemia are found globally, but a high frequency is observed around the Mediterranean basin, in the Middle East, in the Indian subcontinent, and in Southeast Asia, so called the thalassemia belt. This article aims to review the history and factors of spreading of thalassemia, to identify the burden of the disease on individuals, population, and public health, and the issues that thalassemia patients have experienced during the pandemic of COVID-19. Online literature and previous studies on the disease are used to prepare this article. We identified various factors that have contributed to the spread of thalassemia in the last decades and affected the health condition of individuals and population. The recent worldwide pandemic of COVID-19 worsened the situation and made it more complicated for most patients, especially in the emerging countries.

Gene sequencing of Pseudomonas aeruginosa isolated from thalassemia patients in Thi-Qar Governorate

Gene sequencing of Pseudomonas aeruginosa isolated from thalassemia patients in Thi-Qar Governorate

Soluble Fms-like tyrosine kinase-1 as an endothelial dysfunction biomarker associated with pulmonary hypertension in adult patients with beta-thalassemia major.

The etiology of vascular problems in beta-thalassemia has been linked to endothelial damage. Antiangiogenic proteins such as soluble Fms-like tyrosine kinase-1 (sFLT-1) inhibit the signaling of vascular endothelial growth factor and placental growth factor, resulting in a decrease in the development of new blood vessels. Additionally, they promote the maturation of existing blood vessels and lead to endothelial dysfunction. This study aimed to assess the role of sFLT-1 in adult patients with beta-thalassemia major (TM) as a biomarker of endothelial dysfunction and its association with pulmonary hypertension (PHT). A total of 90 subjects were recruited and categorized into two groups: 45 patients with beta-TM, who were further divided based on the presence or absence of PHT, and 45 healthy individuals served as a control group. Serum sFLT-1 was determined using the enzyme-linked immunosorbent assay technique. The results revealed that Beta-TM patients had higher sFLT-1 levels than the control group. In addition, patients with PHT had significantly higher sFLT-1 levels compared to those without PHT. The levels of sFLT-1 were positively correlated with von Willebrand factor, serum ferritin, and high-sensitivity C-reactive protein. Regression analyses demonstrated a significant association between high sFLT-1 levels and the occurrence of PHT. Additionally, sFLT-1 (at a cutoff value of 8.84 pg/mL) demonstrated a sensitivity of 83.30% and a specificity of 80.0% in diagnosing thalassemic patients with PHT. In conclusion, beta-TM patients with elevated serum levels of sFLT-1 are at risk of developing endothelial dysfunction and subsequent development of PHT.

Sociodemographic Determinants of Adherence and Treatment Efficacy in Paediatric Thalassemia Patients from Sarbaz-Rask, Iran

Sociodemographic Determinants of Adherence and Treatment Efficacy in Paediatric Thalassemia Patients from Sarbaz-Rask, Iran