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Genetic manipulation of hematopoietic stem cells (HSCs) is being developed as a therapeutic strategy for several inherited disorders. This field is rapidly evolving with several novel tools and techniques being employed to achieve desired genetic changes. While commercial products are now available for sickle cell disease, transfusion-dependent β-thalassemia, metachromatic leukodystrophy and adrenoleukodystrophy, several challenges remain in patient selection, HSC mobilization and collection, genetic manipulation of stem cells, conditioning, hematologic recovery and post-transplant complications, financial issues, equity of access and institutional and global preparedness. In this report, we explore the current state of development of these therapies and provide a comprehensive assessment of the challenges these therapies face as well as potential solutions. [ABSTRACT FROM AUTHOR]

Hemoglobinopathies are a group of autosomal recessive disorders characterized by either a reduced synthesis of one or more normal globin chains or the synthesis of a structurally abnormal globin chain or, in a few cases, by both that is, the reduced synthesis of a haemoglobin (Hb) variant. Depending on the mutations, these patients may exhibit distorted Hb patterns along with altered red cell indices, both of which can be used to support identification by diagnostic tools. The approach in the diagnosis of hemoglobinopathies and thalassemia depends upon the target geographical population and aim of testing. Red cell indices, Hb pattern analysis on high-performance liquid chromatography, and Hb capillary-zone electrophoresis are the first-line screening tests, and molecular testing helps confirm the diagnosis and is also useful in prenatal and preimplantation genetic diagnosis. Thalassemia patients need lifelong medical care, receiving trasfusions and supplemental therapies, and therefore, timely diagnosis and screening is essential. In the present paper, we review the potential pitfalls and interfering factors in their diagnosis. [ABSTRACT FROM AUTHOR]

Infertility is a common issue that threatens couples worldwide. Infertility can result from the male or female partner alone, or both partners. It can be due to multiple factors related to the patient's overall health or lifestyle. Causes related to patient health can be systemic or related to gonadal dysfunction. One of the systematic causes can be hematological. The two most common hemoglobinopathies that are thought to cause infertility, especially male infertility, are sickle cell disease (SCD) and thalassemia major (TM). These two hemoglobinopathies cause male infertility through pathophysiological alterations. Specifically, they alter the oxygen carrying ability of red blood cells (RBCs), causing tissue hypoxia that affects the normal physiological process of spermatogenesis, eventually inducing infertility. Semen analyses and other systemic blood testing can be used to investigate male infertility. Both hemoglobinopathies can be helped by blood transfusions, which can then alleviate male infertility. This paper aims to explore the relationship between hemoglobinopathies (SCD and TM) and their role in contributing to male infertility, in addition to the role of blood transfusions in addressing male infertility by correcting the root cause. [ABSTRACT FROM AUTHOR]

Thalassemic osteopathy includes low bone mass and impaired bone microarchitecture. We aimed to evaluate the prevalence and determinants of bone quantity (osteoporosis) and quality (microarchitecture) in a cohort of adult patients with transfusion-dependent thalassemia (TDT). Patients with TDT (n = 63) and age- and BMI-matched controls (n = 63) were recruited in the study. Areal bone mineral density (BMD) was measured using DXA Hologic scanner. P1NP and β-CTX were estimated by electrochemiluminescence assay. Bone geometry and volumetric BMD (vBMD) were estimated by second-generation high-resolution peripheral quantitative computed tomography. Bone turnover marker β-CTX was significantly lower in the TDT group, but there was no difference in P1NP levels. Low bone mass (Z ≤ −2) was present in greater proportion of patients both at lumbar spine (LS) (54 vs 0%; p = .001) and femoral neck (FN) (33 vs 8%; p = .001). Hypogonadism was associated with low BMD at FN (OR 10.0; 95% CI, 1.2–86; p = .01) and low hemoglobin with low BMD at LS (OR 1.58; 95% CI, 0.96–2.60; p = .07). The mean trabecular bone score was also significantly lower in patients compared with controls (1.261 ± 0.072 vs 1.389 ± 0.058). Total, cortical and trabecular vBMD were significantly lower in cases than controls. The trabecular number and cortical thickness were significantly lower and trabecular separation higher in cases than controls. Adults with TDT have significantly lower areal, cortical and trabecular vBMD. The bone microarchitecture is also significantly impaired in terms of lower number and wider spacing of trabeculae as well as lower cortical thickness and area at both radius and tibia. Graphical Abstract Lay Summary: Bone quantity and quality are likely to be affected in patients with thalassemia who are dependent on regular blood transfusions. This study evaluated bone health in adults with transfusion-dependent thalassemia (TDT) by comparing bone density and microarchitecture with age- and BMI-matched controls. Adults with TDT had significantly lower bone mineral density (both areal and volumetric), suggesting low bone quantity compared to healthy controls. Trabecular and cortical microarchitecture were also adversely affected, suggesting impaired bone quality. Overall, the study highlights that adults with TDT have significantly compromised bone quantity and quality, increasing their risk for osteoporosis and related fractures. [ABSTRACT FROM AUTHOR]

Background: Quantitative detection of glucose-6-phosphate dehydrogenase (G6PD) is commonly done to screen for G6PD deficiency. However, current reference intervals (RIs) of G6PD are unsuitable for evaluating G6PD-activity levels with local populations or associating G6PD variants with hemolysis risk to aid clinical decision-making. We explored appropriate RIs and clinical decision limits (CDLs) for G6PD activity in individuals from Guangzhou, China. Methods: We enrolled 5,852 unrelated individuals between 2020 and 2022 and screened their samples in quantitative assays for G6PD activity. We conducted further investigations, including G6PD genotyping, thalassemia genotyping, follow-up analysis, and statistical analysis, for different groups. Results: In Guangzhou, the RIs for the G6PD activities were 11.20–20.04 U/g Hb in male and 12.29–23.16 U/g Hb in female. The adjusted male median and normal male median (NMM) values were 15.47 U/g Hb and 15.51 U/g Hb, respectively. A threshold of 45% of the NMM could be used as a CDL to estimate the probability of G6PD variants. Our results revealed high hemolysis-risk CDLs (male: <10% of the NMM, female: <30% of the NMM), medium hemolysis-risk CDLs (male: 10%–45% of the NMM, female: 30%–79% of the NMM), and low hemolysis-risk CDLs (male: ≥45% of the NMM, female: ≥79% of the NMM). Conclusions: Collectively, our findings contribute to a more accurate evaluation of G6PD-activity levels within the local population and provide valuable insights for clinical decision making. Specifically, identifying threshold values for G6PD variants and hemolysis risk enables improved prediction and management of G6PD deficiency, ultimately enhancing patient care and treatment outcomes. [ABSTRACT FROM AUTHOR]

Iron overload causes cognitive impairment in thalassemia patients. The gut-brain axis plays an important role in cognitive function. However, the association between gut/blood microbiome, cognition, and iron burden in thalassemia patients has not been thoroughly investigated. We aimed to determine those associations in thalassemia patients with different blood-transfusion regimens. Sixty participants: healthy controls, transfusion-dependent thalassemia (TDT) patients, and non-transfusion-dependent (NTDT) patients, were recruited to evaluate iron overload, cognition, and gut/blood microbiome. TDT patients exhibited greater iron overload than NTDT patients. Most thalassemia patients developed gut dysbiosis, and approximately 25% of the patients developed minor cognitive impairment. Increased Fusobacteriota and Verrucomicrobiota with decreased Fibrobacterota were observed in both TDT and NTDT groups. TDT patients showed more abundant beneficial bacteria: Verrucomicrobia. Iron overload was correlated with cognitive impairment. Increased Butyricimonas and decreased Paraclostridium were associated with higher cognitive function. No trace of blood microbiota was observed. Differences in blood bacterial profiles of thalassemia patients and controls were insignificant. These findings suggest iron overload plays a role in the imbalance of gut microbiota and impaired cognitive function in thalassemia patients. Harnessing probiotic potential from those microbes could prevent the gut-brain disturbance in thalassemia patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Concurrent recurrence of acute disseminated encephalomyelitis (ADEM) and poststreptococcal glomerulonephritis (PSGN) in a thalassemia intermedia patient is rare and underscores the complexity of autoimmune disorders. This case emphasizes the importance of considering ADEM in the differential diagnosis of children presenting with PSGN accompanied by neurological symptoms. Post‐streptococcal glomerulonephritis (PSGN) is a common group A streptococcal (GAS) infection sequela. The pathophysiology of PSGN involves immune complex deposition, with type 3 hypersensitivity reaction triggered by GAS. Certain neurological conditions may also arise following a GAS infection, possibly due to molecular mimicry in the brain, a pathophysiology similar to rheumatic fever, another common sequel of GAS infection. We present the case of a child with β‐thalassemia intermedia who exhibited the classic triad (edema, hypertension, hematuria) of PSGN along with neurological manifestations, including a low glasgow coma scale (GCS) score and seizures. Magnetic resonance imaging (MRI) of the brain indicated changes consistent with acute disseminated encephalomyelitis (ADEM). Initially treated with methylprednisolone, the patient eventually received intravenous immunoglobulin (IVIG) due to lack of response. The patient had a good outcome, with complete resolution of all symptoms and no residual neurological deficits. This case underscores the importance of considering ADEM in the differential diagnosis for patients presenting with neurological signs and symptoms following a recent throat infection with GAS. Furthermore, given the increased risk of infection in thalassemia, patients with thalassemia who have a throat infection and neurological symptoms should be evaluated for the possible presence of ADEM. [ABSTRACT FROM AUTHOR]

Objective: In thalassemia major, repeated blood transfusions result in iron overload causing organ damage. The objective of this study was assessment of liver enzymes in patients with Thalassemia major and to observe their association with ferritin. Method: A cross-sectional study was performed, at Islamabad Medical and Dental College and its affiliated Akbar Niazi Teaching Hospital from November 2021 till August 2022. Serum ferritin, AST, ALT, and total bilirubin levels were determined, in 135 patients of beta thalassemia major receiving transfusions. Data analysis was performed using SPSS Version 20. For categorical variables, calculation of frequencies and percentages was performed. Mean (± standard deviation) was determined for quantitative variables. ANOVA with post hoc Tukey’s test was used for determining association between liver enzymes and serum ferritin. A p-value of <0.05 was considered significant. The correlation between ferritin and LFTs was determined by Pearson’s correlation coefficient. Results: Patients had an age range of 7-30 years, and males constituted 51% of sample. Mean level of ferritin was 6062.61 + 3641.79 ng/ml, with an insignificant difference between the genders (p =0.366). The levels of AST, ALT and bilirubin were perceived to show a significant increase in patients with ferritin levels >5000ng/ml, when compared with patients having ferritin levels < 2,500 ng/ml. A significant positive correlation of increasing serum ferritin levels was observed with ALT (r= 0.682), to a lesser extent with AST (r = 0.532), and only a weak correlation with serum bilirubin (r = 0.350) Conclusion: Liver damage was caused by increased iron deposition. LFTs should be performed regularly to detect and reduce liver damage by increasing chelation therapy, thereby reducing morbidity and mortality due to thalassemia. [ABSTRACT FROM AUTHOR]

Neutrophil dysfunction is a form of immune suppression in patients with β-thalassemia (Beta-thal), although data on this are limited. In this study, blood from patients and healthy volunteers was analyzed. Flow cytometry analysis demonstrated an increase in immature neutrophils (CD16− CD62L+) and aged (senescent) neutrophils (CD16+ CD62L−) in Beta-thal patients compared to healthy volunteers. The Beta-thal neutrophils demonstrated less prominent chemotaxis and phagocytosis than healthy neutrophils at the baseline. With phorbol myristate acetate (PMA) or lipopolysaccharide (LPS) stimulations, some of the indicators, including the flow cytometry markers (CD11b, CD62L, CD66b, CD63, apoptosis, and reactive oxygen species) and neutrophil extracellular traps (NETs; detected by anti-citrullinated histone 3 immunofluorescence), were lower than the control. Additionally, low-density neutrophils (LDNs), which are found in the peripheral blood mononuclear cell (PBMC) fraction, were observed in Beta-thal patients but not in the control group. The expression of CD11b, CD66b, CD63, arginase I, and ROS in LDNs was higher than the regular normal-density neutrophils (NDNs). The proliferation rate of CD3+ T cells isolated from the PBMC fraction of healthy volunteers was higher than that of the cells from patients with Beta-thal. The incubation of red blood cell (RBC) lysate plus ferric ions with healthy NDNs transformed the NDNs into the aged neutrophils (decreased CD62L) and LDNs. In conclusion, iron overload induces neutrophil diversity along with some dysfunctions. [ABSTRACT FROM AUTHOR]

Patients with sickle cell disease (SCD) in Germany exhibit a substantial genetic diversity in the β‐globin genotype. Data collected by the national German SCD registry reflect this diversity and allowed us to analyze the phenotypes associated with different SCD genotypes. Our study focused on 90 patients with HbS/β‐thalassaemia (HbS/β‐thal) and compared these to patients with HbSS and HbSC. Patients with HbS/β‐thal were classified into three groups: HbS/β0‐thal (no HbA), HbS/β+‐thal (HbA < 14%), and HbS/β++‐thal (HbA≥14%). In comparison to HbSS, patients with HbS/β++‐thal had higher Hb‐levels, lower hemolytic activity and rarely required red blood cell transfusions. HbS/β0‐thal and HbS/β+‐thal closely resembled each other and are jointly referred to as HbS/β0/+‐thal. Compared to HbSS, patients with HbS/β0/+‐thal experienced a similar frequency of vasoocclusive crises and degree of hemolysis. However, the frequency of red blood cell transfusions (0.6 vs. 0.39/year, p =.0049) and splenic sequestration crises (42.4 vs. 15.5% of patients, p = 3.799e‐05) was higher in HbS/β0/+‐thal than in HbSS, but close to zero in HbS/β++‐thal. In conclusion, the level of HbA expression determines the phenotype of HbS/β+‐thal. HbS/β‐thal expressing no or little HbA is hematologically similar to HbSS, but causes a previously unknown high risk of splenic sequestration. [ABSTRACT FROM AUTHOR]

Background: Third-generation sequencing (TGS) based on long-read technology has been gradually used in identifying thalassemia and hemoglobin (Hb) variants. The aim of the present study was to explore genotype varieties of thalassemia and Hb variants in Quanzhou region of Southeast China by TGS. Methods: Included in this study were 6,174 subjects with thalassemia traits from Quanzhou region of Southeast China. All of them underwent common thalassemia gene testing using the DNA reverse dot-blot hybridization technology. Subjects who were suspected as rare thalassemia carriers were further subjected to TGS to identify rare or novel α- and β-globin gene variants, and the results were verified by Sanger sequencing and/or gap PCR. Results: Of the 6,174 included subjects, 2,390 (38.71%) were identified as α- and β-globin gene mutation carriers, including 40 carrying rare or novel α- and β-thalassemia mutations. The αCD30(−GAG)α and Hb Lepore-Boston-Washington were first reported in Fujian province Southeast China. Moreover, the βCD15(TGG> TAG), βIVS−II−761, β0-Filipino(~ 45 kb deletion), and Hb Lepore-Quanzhou were first identified in the Chinese population. In addition, 35 cases of Hb variants were detected, the rare Hb variants of Hb Jilin and Hb Beijing were first reported in Fujian province of China. Among them, one case with compound αααanti3.7 and Hb G-Honolulu variants was identified in this study. Conclusion: Our findings may provide valuable data for enriching the spectrum of thalassemia and highlight the clinical application value of TGS-based α- and β-globin genetic testing. [ABSTRACT FROM AUTHOR]

Accurate and timely interpretation of microcytic anemia can be diagnostically challenging in the primary care setting. We sought to develop a novel model for distinguishing iron-deficiency anemia from thalassemia trait in the modern pediatric population. Demographic history and red blood cell indices were retrospectively characterized for 76 children referred to our pediatric hematology clinic for evaluation of microcytic anemia. Statistically significant variables were sequentially added into a logistic regression model to develop the final model. The final discriminating model incorporates red cell distribution width, mean corpuscular hemoglobin concentration, and red blood cell values. Favorable predictive performance is seen in the initial (sensitivity 89.2%, specificity 92.3%) and external validation cohort (sensitivity 84.4%, specificity 88.9%). This novel tool may aid in determining the cause of hypochromic, microcytic anemia in the primary care setting. Finally, the study cohort reflects an underrepresented group in the development of screening tools, and thus offers generalizability. [ABSTRACT FROM AUTHOR]

Single abnormal gene structure of disorders, specifically the alpha (α) and beta (β) thalassemia recessive disorders are focused. From the NCBI website, the preferred DNA sequencing is downloaded. The objective is to study the structure of Single Abnormal Gene using modified Box counting principle and FFD-Fuzzy Fractal Dimension analysis. Initially the fractal dimension method is used and analyzed single abnormal gene structure with the help of box counting method where the grids are segmented into triangles. Further the analysis is enhanced through grid and triangular method of improved box counting methods named as Ruby Triangular dimension which is the novelty of the research. Comparison of Grid Dimension with Triangular Dimension based fractal and fuzzy fractal dimension in the severity of disease from its secondary structure of the disorder related genes structures are performed. Further the complexity of the Single Abnormal Gene structure evaluated to generate a unique Attractor for the prediction of the α-thalassemia and β-thalassemia disorder in earlier diagnosis, refer as bifurcation theory. The results shows that the triangular Ruby Dimension based improved box counting method facilitate quick with more exactitude. In grid method the size of the image should be 2n pixels and shrink to at most 2048 pixels, whereas the triangular pixels may be reduced to 23 times than grid method. Hence, this novel Fuzzy Fractal Ruby Triangular Dimension method shows better results and can be applied for image of higher dimensions with the same procedure. [ABSTRACT FROM AUTHOR]

Background and Objectives: Adrenal insufficiency (AI) can be a significant concern in patients with transfusion-dependent homozygous beta thalassemia (bThal) due to the chronic disease burden and frequent blood transfusions that these patients require. The prevalence of AI in this population remains unclear, with studies often lacking control groups for comparison. This meta-analysis aimed to estimate the proportion of patients with transfusion-dependent bThal who exhibit evidence of AI. Materials and Methods: A systematic review following PRISMA guidelines identified 19 studies for analysis. Results: Despite the variability in the diagnostic methods used to ascertain AI, the meta-analysis revealed that approximately one-third of patients had evidence of AI, with the prevalence rising to 50% in studies focused on adults with bThal. Conclusions: These findings suggest an increased risk of AI in patients with bThal compared to the general population. Clinicians should consider tailored management strategies, including glucocorticoid coverage during surgical procedures, to mitigate the risk of adrenal crises in this vulnerable patient group. Further research is needed to optimize adrenal surveillance and management in patients with bThal. [ABSTRACT FROM AUTHOR]

Background: Thalassemia is a common monogenic disorder, and children with β-thalassemia major require regular blood transfusions and iron removal therapy. Klinefelter syndrome (KS) is a common sex chromosome abnormality, and 48,XXYY is rare. This report is the first to describe a fetus with a karyotype of 48,XXYY in prenatal diagnosis of β-thalassemia major. Methods: Amniotic fluid was collected by puncture for the prenatal diagnosis of thalassemia, and chromosomal karyotyping was also performed. PCR and reverse dot-blot hybridization (PCR-RDB) were used to identify 17 common β-thalassemia mutations in China. Karyotype analysis of amniotic fluid was performed. Results: The results of PCR-RDB revealed that the genotype of the fetus was a homozygote of CDs41-42 (-TTCT) in the HBB gene. The karyotype analysis displayed that the fetus had Klinefelter syndrome (KS), and the karyotype was the rare 48,XXYY. The fetus was diagnosed with β-thalassemia major and KS. Conclusions: An unexpected detection of the rare 48,XXYY in the prenatal diagnosis of a fetus with β-thalassemia major. There is a pitfall of genetic counseling and prenatal diagnosis in China. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objective: To assess the immunization efficacy and incidence of adverse reactions after hepatitis B vaccination in children with thalassemia based on data from real-world studies. Methods: A total of 625 children were recruited into this cross-sectional study. Subgroup analyses of different thalassemia types were performed using binary logistic regression, the factors affecting HBsAb levels were identified using multiple linear regression, and the dose-response relationship between the duration of immunization and seroconversion was explored using the restricted cubic spline (RCS) model to further assess the protective duration of the hepatitis B vaccine. Results: HBsAb positivity in enrolled children was 87.3% in the thalassemia group and 81.4% in the control group. Multifactorial analysis revealed that the duration of immunization, age at completion of vaccination, and whether the first dose was delayed were significant factors influencing HBsAb levels in children (P < 0.05). The threshold for HBsAb positivity may be reached when the immunization duration reaches approximately 30 months. A subgroup analysis revealed that the HBsAb positivity rate was lower in children with β-thalassemia minor compared to those with α-thalassemia minor (P = 0.001, 95% CI: 0.097 ∼ 0.536). Adverse reactions after hepatitis B vaccination were dominated by general reactions, with a statistically significant difference in injection-site redness and swelling between the thalassemia and control groups (P < 0.05). Conclusions: The immunization response to the hepatitis B vaccine in children with thalassemia minor was comparable to healthy children, with no abnormal adverse effects seen. [ABSTRACT FROM AUTHOR]

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 1 µM; 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 (∼5 min) 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 0.0015 μM, 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 (5 min). 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. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop and assess a novel reverse dot blot assay for the simultaneous detection of 10 types of α-thalassemia alleles in the Chinese population, including six common variants of-SEA, -α3.7, -α4.2, αCS, αQS, and αWS, and four rare variants of αααanti-4.2, αααanti-3.7, --FIL deletion and--THAI deletion. Methods: The novel thalassemia gene assay utilized a two-tier multiplex polymerase chain reaction amplification system and one round of hybridization. Genomic DNA samples were sourced from three hospitals in southern China. Each clinically validated DNA sample was re-evaluated using the new multiplex polymerase chain reaction/reverse dot blot assay III(M-PCR/RDB III). Results: The study analyzed a total of 1,148 unrelated participants, consisting of 810 thalassemia patients and 338 healthy control subjects. Valid hybridization results were obtained for 1,147 samples, with one case (thalassemia carrier) being excluded from the study due to the poor quality of DNA. All 1,147 samples, including those with α heterozygous thalassemia, α homozygous thalassemia, α compound heterozygous thalassemia, and control subjects were accurately genotyped, showing 100% concordance with the reference assays. Conclusion: The novel M-PCR/RDB III assay proved to be simple, rapid, and precise, indicating its potential for genetic screening and clinical diagnosis of both common and rare α-thalassemia variants in Chinese populations. [ABSTRACT FROM AUTHOR]

Objective To analyze and evaluate the prevention and control policies for thalassemia, identify the usage and distribution of policy tools, as well as the advantages and disadvantages of the policies, and propose improvement suggestions. Methods From the perspective of policy instruments, an analytical framework of "policy tools-stakeholders" has been constructed. Utilizing the Policy Modeling Consistency (PMC) index model, a quantitative evaluation was conducted. The characteristics of policy tool usage were identified, problems in the policies were discovered, and strategies for policy optimization were explored. Results The study found that the overall quality of Guangxi's thalassemia prevention and control policies is relatively high, but there are also issues such as fewer joint documents issued by multiple departments, lack of demand-oriented policy tools (18.46%), slightly vague policy nature, and difficulty in balancing long-term and short-term policy effectiveness. Conclusion The prevention and treatment policy for Mediterranean anemia should start by enhancing the utilization of demand-driven tools, taking into account the short-term and long-term effectiveness of the policy, and mobilizing the participation of multiple stakeholders to improve policy quality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The effective management of iron overload in transfusion-dependent thalassemia (TDT) requires adherence to iron chelation therapy (ICT). However, adherence rates among pediatric thalassemia patients remain suboptimal. This study aimed to evaluate adherence levels and identify sociodemographic and clinical factors impacting ICT adherence in pediatric TDT patients from Sarbaz-Rask, Iran. Methods: This cross-sectional study assessed 58 pediatric TDT patients aged 2–18 years at a thalassemia clinic from April 2021 to March 2022. Adherence was evaluated using the medication possession ratio. Logistic regression and correlation analyses identified predictors of adherence and treatment efficacy based on serum ferritin levels. Results: Adherence was satisfactory in 58.6% of patients and associated with younger maternal age (93.8% for 18–30 years, p = 0.008) and urban residency (p = 0.02). Logistic regression identified urban residency (OR = 20.265, p = 0.073) and a maternal age of 18–30 years (OR = 39.236, p = 0.005) as key predictors of adherence. Adherence was not significantly influenced by having a sibling with thalassemia or the maternal educational level. Treatment efficacy was observed in 27.6% of patients. Maternal age impacted adherence in poorly controlled patients (p = 0.007). Urban residents showed higher adherence rates, particularly with poor control (p = 0.017). Conclusions: Younger maternal age and urban residency emerged as positive predictors of adherence and treatment efficacy in pediatric thalassemia patients from Sarbaz-Rask. Targeted interventions supporting rural families and those with older maternal caregivers may improve adherence and outcomes in this population. [ABSTRACT FROM AUTHOR]

Background Hemoglobin (Hb) Hekinan II (A27; Glu-Asp) is an α-chain variant, and its interaction with the common Southeast Asian (--SEA/) α-thalassemia (α-thal) deletion is rarely reported. This study provides a clinical update of Hb Hekinan II associated with (--SEA/) α-thal. Methods A total of 11 simple heterozygotes and 20 composite heterozygotes for Hb Hekinan II and (--SEA/) α-thal were included based on molecular diagnosis. Results Hb Hekinan II exhibited a significant increase in hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin content, but a decrease in red blood cell level compared with α+ thalassemia deletion. Compared with (--SEA/) α-thal, composite heterozygotes for Hb Hekinan II and (--SEA/) α-thal showed similar erythrocyte parameters. Both heterozygotes with and without (--SEA/) α-thal showed low Hb A2 level. Hb Hekinan II showed abnormal performance in high-performance liquid chromatography but not in capillary electrophoresis. Conclusion Hb Hekinan II is a benign Hb variant. The heterozygotes exhibit clinically asymptomatic coinheritance with (--SEA/) α-thal having comparable hematological phenotype to simple (--SEA/) α-thal. The combination of hematological and molecular analysis helped to improve the detection rate of this rare variant. [ABSTRACT FROM AUTHOR]

Increased liver stiffness (LS) can be result of increased liver iron concentration (LIC) which may not yet be reflected in the liver fibrotic status. The objective of our study was to examine relationship between hemochromatosis, LS, and serum ferritin level in transfusion-dependent patients. We recruited all 70 transfusion-dependent patients, whose median age was 15, referred for evaluating LIC status by magnetic resonance imaging (MRI) followed by two-dimensional ultrasonography shear wave elastography (2D-SWE). Thalassemia beta affected the majority of the patients. The optimal cut point for prediction of severe hemochromatosis using median SWE (kPa) and SWV (m/s) was ≥ 7.0 kPa and ≥ 1.54 m/s, respectively, with sensitivity of 0.76 (95% confidence interval [CI] 0.55, 0.91) and, specificity of 0.69 (95%CI 0.53, 0.82). When combing the optimal cut point of SWE (kPa) at ≥ 7.0 and serum ferritin ≥ 4123 ng/mL, the sensitivity increased to 0.84 (95%CI 0.64, 0.95) with specificity of 0.67 (95%CI 0.50, 0.80), positive predictive value (PPV) of 0.60 (95%CI 0.42, 0.76), and negative predictive value (NPV) of 0.88 (95%CI 0.71, 0.96). Simultaneous tests of 2D-SWE and serum ferritin for prediction of severe hemochromatosis showed the highest sensitivity of 84% (95%CI 0.64–0.95), as compared to 2D-SWE alone at 76% (95%CI 0.55, 0.91) or serum ferritin alone at 44% (95%CI 0.24–0.65). We recommend measuring both 2D-SWE and serum ferritin in short interval follow up patients. Adding 2D-SWE to management guideline will help in deciding for aggressive adjustment of iron chelating medication and increased awareness of patients having severe hemochromatosis. [ABSTRACT FROM AUTHOR]

To investigate the feasibility and diagnostic efficacy of a 3D multiecho Dixon (qDixon) research application for simultaneously quantifying the liver iron concentration (LIC) and steatosis in thalassemia patients. This prospective study enrolled participants with thalassemia who underwent 3 T MRI of the liver for the evaluation of hepatic iron overload. The imaging protocol including qDixon and conventional T2* mapping based on 2D multiecho gradient echo (ME GRE) sequences respectively. Regions of interest (ROIs) were drawn in the liver on the qDixon maps to obtain R2* and proton density fat fraction (PDFF). The reference R2* value was measured and calculated on conventional T2* mapping using the CMRtools software. Correlation analysis, Linear regression analysis, and Bland–Altman analysis were performed. 84 patients were finally included in this study. The median R2*-ME-GRE was 366.97 (1/s), range [206.68 (1/s), 522.20 (1/s)]. 8 patients had normal hepatic iron deposition, 16 had Insignificant, 42 had mild, 18 had moderate. The median of R2*-qDixon was 376.88 (1/s) [219.33 (1/s), 491.75 (1/s)]. A strong correlation was found between the liver R2*-qDixon and the R2*-ME-GRE (r = 0.959, P < 0.001). The median value of PDFF was 1.76% (1.10%, 2.95%). 8 patients had mild fatty liver, and 1 had severe fatty liver. MR qDixon research sequence can rapidly and accurately quantify liver iron overload, that highly consistent with the measured via conventional GRE sequence, and it can also simultaneously detect hepatic steatosis, this has great potential for clinical evaluation of thalassemia patients. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this cross-sectional study was to investigate the association of left atrial (LA) strain parameters with demographics, clinical data, cardiovascular magnetic resonance (CMR) findings, and cardiac complications (heart failure and arrhythmias) in a cohort of patients with β-thalassemia major (β-TM). Materials and methods: We considered 264 β-TM patients (133 females, 36.79 ± 11.95 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) project. Moreover, we included 35 sex- and age-matched healthy controls (14 females, mean age 37.36 ± 17.52 years). Reservoir, conduit, and booster LA functions were analysed by CMR feature tracking using dedicated software. Results: Compared to the healthy control group, β-TM patients demonstrated lower LA reservoir strain and booster strains, as well as LA reservoir and booster strain rates. However, no differences were found in LA conduit deformation parameters. In β-TM patients, ageing, sex, and left ventricle (LV) volume indexes were independent determinants of LA strain parameters. The number of segments with late gadolinium enhancement (LGE) significantly correlated with all LA strain parameters, with the exception of the LA conduit rate. Patients with cardiac complications exhibited significantly impaired strain parameters compared to patients without cardiac complications. Conclusion: In patients with β-TM, LA strain parameters were impaired compared to control subjects, and they exhibited a significant correlation with the number of LV segments with LGE. Furthermore, patients with cardiac complications had impaired left atrial strain parameters. Clinical relevance statement In patients with β-thalassemia major, left atrial strain parameters were impaired compared to control subjects and emerged as a sensitive marker of cardiac complications, stronger than cardiac iron levels. Key Points: • Compared to healthy subjects, β-thalassemia major patients demonstrated significantly lower left atrial reservoir strain and booster strains, as well as left atrial reservoir and booster strain rates. • In β-thalassemia major, ageing, sex, and left ventricular volume indexes were independent determinants of left atrial strain parameters, while left atrial strain parameters were not correlated with myocardial iron overload. • An independent association between reduced left atrial strain parameters and a history of cardiac complications was found in β-thalassemia major patients. [ABSTRACT FROM AUTHOR]

Adipocyte fatty acid-binding protein (A-FABP; FABP4) plays a significant role in the pathogenesis and progression of metabolically driven low-grade inflammation and organ damage. This study aimed to evaluate the performance of circulating FABP4 as a predictive and diagnostic biomarker for thalassemia-associated cardiometabolic events. This case-control study enrolled 50 adults with β-thalassemia and 30 age-, sex-, and body mass index-matched controls. Participants underwent a comprehensive evaluation, including complete blood count, liver and kidney function tests, serum blood glucose, lipid profile, and ferritin levels, pelviabdominal ultrasound, ECG, and echocardiography after taking a full medical history and conducting a clinical examination. Serum levels of FABP4 were measured using an Enzyme-Linked-Immunosorbent-Assay. The diagnostic performance of FABP4 was assessed using receiver operator characteristic (ROC) curve analysis to determine optimal values for excluding and confirming cardiometabolic metflammation. The thalassemia cohort exhibited a statistically significant higher concentration of FABP4 compared to the control group (p-value < 0.001). Positive correlations were found between FABP4 and ferritin serum levels above 800 or 1000 ug/L, as well as with ALT, TGS, and LDL (p-value < 0.05). Circulating FABP4 was identified as a statistically significant risk factor for thalassemia-associated cardiometabolic comorbidities (OR = 84.00, 95%CI:18.6–378.6, p-value < 0.001). ROC analysis determined that the FABP4 exclusionary cut-off value > 2.30 ng/ml could effectively discriminate between thalassemia-associated adverse metaflammation and controls, while the FABP4 confirmatory cut-off value was > 2.58 ng/ml. In conclusion, circulating FABP4 appears to be a potential risk factor for predicting progression to cardiometabolic events in thalassemia-associated adverse metaflammation. FABP4 holds promise as a diagnostic and prognostic biomarker for disease monitoring and risk stratification. Further validation through large-scale, multicenter, prospective studies is warranted. [ABSTRACT FROM AUTHOR]

Hemoglobinopathies are commonly occurring genetic disorders worldwide. The aim of this study is to determine the biochemical predictors of cerebrovascular complications in pediatric patients with sickle cell anemia. We investigated the relationship between levels of neurological damage markers, such as Serum S100 calcium-binding protein B (S100B), Glial Fibrillary Acidic Protein (GFAP), and Neuron-Specific Enolase (NSE), and radiological findings in these patients. A total of 72 SCD patients and 30 healthy children were included in the study. Clinical and laboratory findings were recorded. Time-averaged maximum mean velocity (TAMMV) values were obtained from transcranial Doppler ultrasonography imaging (TCDI) of the middle cerebral artery. Serum levels of S100B, GFAP, and NSE were measured using the ELISA method both in the SCD group and the control group. Among the patients, 51 had sickle cell anemia (HbSS), 21 had HbSβ0 thalassemia, with 32 (44.4%) being female and 40 (55.6%) male. Their mean age was 12.68 ± 4.56 (ranging from 3 to 24) years old. S100B, GFAP, and NSE serum levels were significantly higher in the SCD group compared to the control group. It was observed that serum levels of S100B, NSE, and GFAP were higher in the group with TAMMV ≥ 170 cm/s. As known, in patients with SCD, the disruption of the blood-brain barrier begins with the occurrence of vaso-occlusive events. Hence, the risk of cerebrovascular events increases. Our study's indication that serum levels of S100B, GFAP, and NSE could be used in predicting or detecting cerebrovascular events in the early stages is noteworthy. [ABSTRACT FROM AUTHOR]

Abstract Iron overload causes cognitive impairment in thalassemia patients. The gut-brain axis plays an important role in cognitive function. However, the association between gut/blood microbiome, cognition, and iron burden in thalassemia patients has not been thoroughly investigated. We aimed to determine those associations in thalassemia patients with different blood-transfusion regimens. Sixty participants: healthy controls, transfusion-dependent thalassemia (TDT) patients, and non-transfusion-dependent (NTDT) patients, were recruited to evaluate iron overload, cognition, and gut/blood microbiome. TDT patients exhibited greater iron overload than NTDT patients. Most thalassemia patients developed gut dysbiosis, and approximately 25% of the patients developed minor cognitive impairment. Increased Fusobacteriota and Verrucomicrobiota with decreased Fibrobacterota were observed in both TDT and NTDT groups. TDT patients showed more abundant beneficial bacteria: Verrucomicrobia. Iron overload was correlated with cognitive impairment. Increased Butyricimonas and decreased Paraclostridium were associated with higher cognitive function. No trace of blood microbiota was observed. Differences in blood bacterial profiles of thalassemia patients and controls were insignificant. These findings suggest iron overload plays a role in the imbalance of gut microbiota and impaired cognitive function in thalassemia patients. Harnessing probiotic potential from those microbes could prevent the gut-brain disturbance in thalassemia patients.

Abstract 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.

Abstract Background Third-generation sequencing (TGS) based on long-read technology has been gradually used in identifying thalassemia and hemoglobin (Hb) variants. The aim of the present study was to explore genotype varieties of thalassemia and Hb variants in Quanzhou region of Southeast China by TGS. Methods Included in this study were 6,174 subjects with thalassemia traits from Quanzhou region of Southeast China. All of them underwent common thalassemia gene testing using the DNA reverse dot-blot hybridization technology. Subjects who were suspected as rare thalassemia carriers were further subjected to TGS to identify rare or novel α- and β-globin gene variants, and the results were verified by Sanger sequencing and/or gap PCR. Results Of the 6,174 included subjects, 2,390 (38.71%) were identified as α- and β-globin gene mutation carriers, including 40 carrying rare or novel α- and β-thalassemia mutations. The αCD30(−GAG)α and Hb Lepore-Boston-Washington were first reported in Fujian province Southeast China. Moreover, the βCD15(TGG> TAG), βIVS−II−761, β0-Filipino(~ 45 kb deletion), and Hb Lepore-Quanzhou were first identified in the Chinese population. In addition, 35 cases of Hb variants were detected, the rare Hb variants of Hb Jilin and Hb Beijing were first reported in Fujian province of China. Among them, one case with compound αααanti3.7 and Hb G-Honolulu variants was identified in this study. Conclusion Our findings may provide valuable data for enriching the spectrum of thalassemia and highlight the clinical application value of TGS-based α- and β-globin genetic testing.

Blood transfusion is the mainstay for management of hemoglobinopathies, including thalassemia and sickle cell disease (SCD). Apart from other transfusion related adverse effects, immunization is a significant complication, particularly in multitransfused recipients. Alloimmunization rates vary widely, both in thalassemia and SCD patients. Alloimmunization complicates the management in form of hemolytic transfusion reactions, difficulty in finding compatible units, delays in transfusion and increasing costs. Exact pathogenesis and prevention modality have not been elucidated. Apart from antigenic differences, immunomodulatory effects and inflammation also play a role in pathogenesis. Ethnic heterogeneity between donors and recipients predisposes to higher alloimmunization.Transfusion management of hemoglobinopathies across the globe is fragmented, with different levels of care. Guidelines propose red cell antigen profiling, transfusion of leucoreduced red cells, preferably matched for Rh and Kell antigens, over and above ABO-D matching. For alloimmunized patients, corresponding antibody negative red cells need to be transfused. However, patients from different backgrounds are variably transfused with whole blood/red cells, which may or may not be leukoreduced. Prophylactic antigen matching reduces the risk of alloimmunization, however, has limitations. RH variants may not be picked up by phenotyping alone. Moreover, the approach of prophylactic antigen matching is expensive, labour intensive, time consuming and may cause delays in transfusions. There is limited, low quality evidence on best practices for transfusion management of SCD and thalassemia. The review analyses the magnitude of problem, factors contributing and modalities for prevention and management of immunization.

Abstract Objective To assess the immunization efficacy and incidence of adverse reactions after hepatitis B vaccination in children with thalassemia based on data from real-world studies. Methods A total of 625 children were recruited into this cross-sectional study. Subgroup analyses of different thalassemia types were performed using binary logistic regression, the factors affecting HBsAb levels were identified using multiple linear regression, and the dose-response relationship between the duration of immunization and seroconversion was explored using the restricted cubic spline (RCS) model to further assess the protective duration of the hepatitis B vaccine. Results HBsAb positivity in enrolled children was 87.3% in the thalassemia group and 81.4% in the control group. Multifactorial analysis revealed that the duration of immunization, age at completion of vaccination, and whether the first dose was delayed were significant factors influencing HBsAb levels in children (P

Aixiang Lv,1,2,&ast; Jingmin Li,1,2,&ast; Meihuan Chen,1,&ast; Wei Wang,3 Liangpu Xu,1 Hailong Huang1,2 1Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital, Fujian Provincial Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, People’s Republic of China; 2College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Plastic Surgery, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangpu Xu; Hailong Huang, Email xiliangpu@fjmu.edu.cn; huanghailong@fjmu.edu.cnPurpose: Thalassemia, an inherited quantitative globin disorder, is the most prevalent monogenic disease globally. While severe alpha thalassemia results in intrauterine death, β-thalassemia manifests during childhood due to the “second conversion of hemoglobin”, garnering increased attention in recent decades.Methods: In this study, a bibliometric analysis was conducted of thalassemia articles published in the Web of Science Core Collection database between 2013 and 2023 to establish a comprehensive overview and to identify emerging trends. A total of 5655 studies published between 2013 and 2023 were systematically retrieved, and annual publications demonstrated a steady increase, maintaining a high level over the past decade.Results: The United States contributed the highest number of publications, followed by China. Notably, the journal Blood emerged as the leading authority in β-thalassemia research. Analysis of research hotspots revealed that the pathogenesis of β-thalassemia is primarily linked to iron overload, anemia, gene mutations, and ineffective erythropoiesis. Furthermore, recent studies focusing on gene editing therapies present promising avenues for future investigation.Conclusion: These findings grasp the research status of β-thalassemia and shed new light on future research frontiers.Keywords: bibliometric, citespace, hotspots, thalassemia, VOSviewer