Thalassemia Reports

12 pages, 915 KB

Open AccessArticle

Association Between Plasma Cystatin C Concentration and Urine Osmolality in Adults with Different Forms of Beta-Thalassemia: A Cross-Sectional Study in Vietnam

by Loan Do Thi Thanh, Anh Nguyen Ngoc, Kien Nguyen Trung, Ha Nguyen Thi Thu, Dung Nguyen Huu and Thang Le Viet

Thalass. Rep. 2026, 16(2), 8; https://doi.org/10.3390/thalassrep16020008 - 6 May 2026

Abstract

Objective: To determine plasma cystatin C concentrations, urine osmolality and their relationship with disease severity in beta-thalassemia patients. Methods: A cross-sectional study was conducted on 234 patients with beta-thalassemia, including equal numbers (78 each) of beta-thalassemia major, intermedia, and minor cases, along with [...] Read more.

Objective: To determine plasma cystatin C concentrations, urine osmolality and their relationship with disease severity in beta-thalassemia patients. Methods: A cross-sectional study was conducted on 234 patients with beta-thalassemia, including equal numbers (78 each) of beta-thalassemia major, intermedia, and minor cases, along with 78 healthy individuals matched for age, sex, and body mass index, who served as the control group. Plasma cystatin C concentrations were quantified in all subjects using the ELISA method, and urine osmolality level was measured automatically on a FISKE 210 machine (USA). Results: The proportion of beta-thalassemia patients with increased plasma cystatin C concentration was 39.3% and the proportion with a decreased urine osmolality level was 67.5% compared with the control group. Plasma ferritin had predictive value for increased plasma cystatin C concentration (cut-off point: 567.5 ng/mL; AUC = 0.803) and decreased urine osmolality level (cut-off point: 488.15 ng/mL; AUC = 0.820), p < 0.001. Plasma cystatin C concentration increased gradually and urine osmolality level decreased gradually from minor beta-thalassemia to intermedia beta-thalassemia to major beta-thalassemia patients, with p < 0.001. Conclusions: Increased plasma cystatin C concentrations and decreased urine osmolality levels are common and are associated with severity in beta-thalassemia patients. Full article

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28 pages, 1280 KB

Open AccessReview

Recent Advances in Thalassemia Management: From Curative Therapies to Artificial Intelligence

by Mohamed Medhat Abdelwahab Gamaleldin, Shaimaa Mahmoud Nashat Sayed Abdelhalim and Ivo Abraham

Thalass. Rep. 2026, 16(2), 7; https://doi.org/10.3390/thalassrep16020007 - 22 Apr 2026

Abstract

Thalassemia is an inherited hemoglobin disorder characterized by chronic hemolytic anemia and substantial long-term healthcare needs. In β-thalassemia major, patients typically require regular red blood cell transfusions with iron chelation to prevent transfusional iron overload. Although supportive care has markedly improved survival, it [...] Read more.

Thalassemia is an inherited hemoglobin disorder characterized by chronic hemolytic anemia and substantial long-term healthcare needs. In β-thalassemia major, patients typically require regular red blood cell transfusions with iron chelation to prevent transfusional iron overload. Although supportive care has markedly improved survival, it is associated with a high treatment burden and does not provide a cure. In recent years, curative and disease-modifying therapies have expanded the treatment landscape. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potentially curative option for selected patients, while autologous gene therapy and gene-editing approaches have shown the capacity to achieve transfusion independence in clinical studies. In parallel, pharmacologic advances—including luspatercept, a transforming growth factor-beta (TGF-β) ligand trap—have been shown to enhance erythropoiesis and reduce transfusion requirements, and emerging agents such as fetal hemoglobin inducers (e.g., thalidomide) and the oral pyruvate kinase activator mitapivat have demonstrated clinically meaningful hemoglobin improvements in selected populations. Adjunctive strategies, including antioxidants, are under investigation to mitigate oxidative stress, and applications of artificial intelligence are increasingly used to support screening, diagnosis, and longitudinal monitoring of iron overload. This review synthesizes recent advances in curative therapies, novel pharmacologic agents, supportive strategies, and AI-enabled tools and highlights priorities for future clinical development and implementation. Full article

(This article belongs to the Collection Feature Papers in Thalassemia Reports)

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12 pages, 813 KB

Open AccessArticle

Implementing Genetic Counseling for Rare Diseases in LMICs: Pediatric and Prenatal Perspectives from India

by Siddannagoud, Dolat Singh Shekhawat, Kuldeep Singh, Varuna Vyas, Pratibha Singh, Charu Sharma, Navdeep Kaur Ghuman and Tanu Gupta

Thalass. Rep. 2026, 16(2), 6; https://doi.org/10.3390/thalassrep16020006 - 1 Apr 2026

Abstract

Background: This study investigated the clinical characteristics of consultands and examined their perceived personal control, satisfaction, and decision-making regarding genetic testing, as well as the factors influencing these outcomes, at a tertiary care center in northwestern India. Methods: Detailed clinical and family histories [...] Read more.

Background: This study investigated the clinical characteristics of consultands and examined their perceived personal control, satisfaction, and decision-making regarding genetic testing, as well as the factors influencing these outcomes, at a tertiary care center in northwestern India. Methods: Detailed clinical and family histories were recorded, and trained genetic professionals provided genetic counseling. Perceived personal control (PPC) was assessed pre- and post-counseling using the PPC (nine-item) questionnaire, while post-counseling satisfaction was measured using the six-item Genetic Counseling Satisfaction Scale (GCSS). Outcomes included awareness of genetic disorders, uptake of genetic testing, and reproductive decision-making. Results: A total of 225 consultands (125 pediatric and 100 antenatal) were enrolled. The most common systemic disorders were: inborn errors of metabolism (21.3%), congenital anomalies (15.2%), neurological disorders (15%), primary immunodeficiencies (12.3%), renal genetic disorders (12.2%), respiratory disorders (12%), thalassemia (9%), endocrine disorders (3.9%), and cardiovascular anomalies (3%). In the pediatric group, socioeconomic status (p = 0.048) and higher education levels (p = 0.02) were significantly associated with higher perceptions of adequate counseling time and overall GCSS. None of the examined factors in the prenatal group showed a statistically significant association with satisfaction scores. Consultands primarily concerned with preventing recurrence in future pregnancies showed significantly higher PPC scores both before (p = 0.026) and after counseling (p = 0.009), with the greatest overall improvement in satisfaction (p = 0.044). In the pediatric group, those with an affected family member showed the greatest post-counseling improvement in PPC. Conclusions: Low education, limited awareness, socioeconomic constraints, delayed presentation and low referral rates were key barriers to effective genetic counseling. Addressing these factors can improve consultand awareness, satisfaction, decision-making, and uptake of genetic testing, thereby enhancing reproductive outcomes in high-risk families. Full article

(This article belongs to the Section Quality of Life)

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9 pages, 247 KB

Open AccessArticle

Iron Overload and Endocrine Dysfunction in Adults with Transfusion-Dependent Beta-Thalassemia and Growth Retardation: A Correlational Study

by Muhammad Hammad, Sadaf Fardoos, Khadija Shakoor and Ali Nasir

Thalass. Rep. 2026, 16(1), 5; https://doi.org/10.3390/thalassrep16010005 - 11 Mar 2026

Abstract

Background and Objective: Iron overload remains a significant clinical concern in patients with transfusion-dependent beta-thalassemia (TDT). This study aims to characterize the iron load and endocrine profile of adult transfusion-dependent beta-thalassemia patients and to evaluate their correlation with growth retardation. Methods: [...] Read more.

Background and Objective: Iron overload remains a significant clinical concern in patients with transfusion-dependent beta-thalassemia (TDT). This study aims to characterize the iron load and endocrine profile of adult transfusion-dependent beta-thalassemia patients and to evaluate their correlation with growth retardation. Methods: A cross-sectional study was conducted at PIMS Hospital, Islamabad, involving 62 adult patients with homozygous or HbE beta-thalassemia receiving regular blood transfusions. Iron overload was assessed using serum ferritin (SF) and transferrin saturation (TS), while endocrine function was evaluated through measurements of thyroid-stimulating hormone-sensitive (TSH), free thyroxine (FT4), and insulin-like growth factor-1 (IGF-1). Data was analyzed using SPSS v26.0 and R v4.3.1, which included Pearson correlation, chi-square testing, and multivariable regression to explore associations between iron indices and endocrine dysfunction. Results: Serum ferritin demonstrated significant negative correlations with FT4 (r = −0.348, p = 0.005) and IGF-1 (r = −0.302, p = 0.015). MRI T2* pancreas values correlated positively with FT4 (r = 0.268, p = 0.037) and IGF-1 (r = 0.312, p = 0.015). Patients with ferritin > 5000 ng/mL exhibited a higher prevalence of low IGF-1 levels (89.2% vs. 64.0%, p = 0.018). No significant gender-based differences were observed in endocrine parameters. Conclusion: Pancreatic iron burden and elevated serum ferritin were significantly associated with impaired thyroid and growth axis function, highlighting the value of integrating MRI T2* and biochemical markers for early endocrine risk stratification in adult TDT patients. Full article

6 pages, 1310 KB

Open AccessBrief Report

Hemoglobinopathy Prevention Program in Immigrants: Equality Plus Education Program

by Duran Canatan, Vincenzo De Sanctis, Joan Lluis Vives Corrons, Giorgio Piacentini, Fatih Kara, Basak Tezel, Aslıhan Ugur Külekci, Özlem Zümrüt, Zekiye Özdemir, Kemal Gürsoy, Gamze Kaymak, Şirin Aydın, Tanju Altunsu, İlhan Aydın, Mustafa Hambolat, Nilgün Keloğlu, Elif Durmaz and Abdullah Solmaz

Thalass. Rep. 2026, 16(1), 4; https://doi.org/10.3390/thalassrep16010004 - 10 Mar 2026

Abstract

Background and aim: Hemoglobinopathies have become an important public health problem due to global migration. The aim of this project was to address the problem of hemoglobinopathy among immigrants living in Türkiye, Spain, and Italy, in addition to training health managers and Syrian [...] Read more.

Background and aim: Hemoglobinopathies have become an important public health problem due to global migration. The aim of this project was to address the problem of hemoglobinopathy among immigrants living in Türkiye, Spain, and Italy, in addition to training health managers and Syrian family physicians at immigrant health centers in the southeastern provinces of Türkiye. Material and methods: A three-year international project, named EQUALITY PLUS, was supported by the European Union Erasmus Project. We planned transnational meetings (TPM), vocational education meetings (VET), and Practical Implementation Meetings (PIEM) for the education program. Results: Four TPMs were held in Türkiye, Spain, and Italy, involving a total of 49 professionals. Two VETs were held in Spain and Italy. A total of 23 professionals attended both VETs. Six PIEMs were held in the southern and southeastern Turkish provinces, such as Adana Mersin, Hatay, Gaziantep, Kilis, and Sanliurfa. A total of 442 people, including 373 Syrian family physicians and 69 provincial health managers, were educated in six provinces in Türkiye. Discussion: While the immigrants to Italy and Spain come mainly from Central and North West African maritime routes, immigrants to Türkiye predominantly come from Syria. Among a total of 4 million Syrian immigrants to Türkiye, 200.000 were found to be carriers of thalassemia. In the refugee camps where Syrian immigrants live, the fertility rate is high and the number of sick newborns is increasing, and birth control, genetic counseling, and prenatal diagnosis methods are not sufficient. This project was intended to serve as a guide to prevent hemoglobinopathy in Syrian immigrants. Further projects are needed to address the fertility rate and increased number of sick newborns in these refugee camps. Family physicians at migrant health centers received training on the prevention of hemoglobinopathies. This training included providing detailed genetic counseling to families and providing prenatal diagnosis and preimplantation genetic diagnosis opportunities. Because of the major earthquake that occurred in this region after the project, the work could not continue and preliminary data could not be obtained. Public health services will follow the results of project and the registered number of sick newborns with hemoglobinopathies. Full article

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16 pages, 5310 KB

Open AccessArticle

Cascade Screening of β-Thalassemia in an Indian Family Using Flow Injection Analysis–Triple Quadrupole Mass Spectrometry: Comparison of Micro Sampling Approaches with Conventional Electrophoresis

by Ankitha K. Puthiyaveettil, Harshini K. Musuvathi and Deepalakshmi D. Putchen

Thalass. Rep. 2026, 16(1), 3; https://doi.org/10.3390/thalassrep16010003 - 24 Feb 2026

Abstract

Background: β-thalassemia is a rare genetic disorder affecting 1–5% of the global population and poses a health burden due to migration of individuals from endemic regions. Identifying asymptomatic β-thalassemia carriers is essential to prevent the birth of thalassemic babies. A simple, sensitive [...] Read more.

Background: β-thalassemia is a rare genetic disorder affecting 1–5% of the global population and poses a health burden due to migration of individuals from endemic regions. Identifying asymptomatic β-thalassemia carriers is essential to prevent the birth of thalassemic babies. A simple, sensitive method compatible with self-sampling could enhance the detection of β-thalassemia in the population. Methods: Capillary blood was collected via dried blood spot (DBS) and dried blood matrix (DBM) from 18 members (52.9%, 18/34) of a three-generation family. Hemoglobin was extracted, and globin chains were analyzed on a triple quadrupole mass spectrometer (TQMS). δ/β (%) was utilized as a biomarker to identify β-thalassemia. Venous blood collected from positive and negative individuals (n = 11) was further tested to confirm the findings and validated with complete blood count (CBC) and Capillary Electrophoresis (CE). Results: β-thalassemia was detected in seven individuals: three from generation I, three from generation II, and one from generation III. CBC showed thalassemia indices, while CE demonstrated elevated HbA2 consistent with β-thalassemia. Molecular sequencing of two samples confirmed the heterozygous c.92 + 5 G > C mutation in the β-globin gene. The overall prevalence of β-thalassemia in the family was 20.6% (7/34). High clinical performance was achieved across sample types, with 100% sensitivity for DBS, 100% specificity for DBM, and an overall accuracy of 91% when compared with CE. Conclusions: TQMS in combination with CBC parameters successfully identified asymptomatic heterozygous β-thalassemia carriers using self-sampling techniques. Cascade screening within affected families emerges as a possible strategy for early detection of β-thalassemia pending comprehensive validation. Full article

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7 pages, 980 KB

Open AccessCase Report

A Heterozygous ABCC6 Variant as a Potential Contributor to Choroidal Neovascularization in a β-Thalassemia Patient

by Debashis Pal, Dipankar Saha, Prosanto Kumar Chowdhury, Arup Das and Anupam Basu

Thalass. Rep. 2026, 16(1), 2; https://doi.org/10.3390/thalassrep16010002 - 29 Jan 2026

Abstract

β-thalassemia patients often experience ocular abnormalities such as angioid streaks (ASs), retinal pigmented epithelium degradation, visual field defects, and in rare instances choroidal neovascularization (CNV). Although ASs are common in individuals with hemoglobinopathies, the occurrence of choroidal neovascularization without preceding ASs is exceptionally [...] Read more.

β-thalassemia patients often experience ocular abnormalities such as angioid streaks (ASs), retinal pigmented epithelium degradation, visual field defects, and in rare instances choroidal neovascularization (CNV). Although ASs are common in individuals with hemoglobinopathies, the occurrence of choroidal neovascularization without preceding ASs is exceptionally rare. In this report, we describe a β-thalassemia patient who had developed CNV at the age of 27 years and also had experience of renal stones at the age of 19 years. He had undergone splenectomy and was under conservative therapy of iron supplementation. We conducted whole-exome sequencing (WES) in search of CNV-associated variants. Through variant filtering and Phenolyzer analysis, we have identified a rare heterozygous missense variant in the ABCC6 gene, ABCC6:NM_001171:exon25:c.3524T>C (rs376062004). In silico analysis revealed that this variant is present in the highly conserved region and is likely to decrease the stability of the protein. Mutation in the ABCC6 gene leads to pseudoxanthoma elasticum (PXE). Previously, it was believed that ASs and subsequent CNV-like ocular complication may develop due to the pathophysiological condition of thalassemia. However, our study provides compelling evidence that rare mutations in the ABCC6 gene, in combination with oxygen insufficiency, may contribute to the development of CNV in β-thalassemia patients. This finding highlights the potential genetic basis of PXE-mediated CNV development in β-thalassemia. Full article

(This article belongs to the Section Quality of Life)

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5 pages, 301 KB

Open AccessEditor’s ChoiceCase Report

The First Gene Therapy for Treating an Indonesian Child with Thalassemia Major: A New Hope for Indonesia

by Edi Setiawan Tehuteru, Teck Onn Lim, Anky Tri Rini Kusumaning Edhy, Ludi Dhyani Rahmartani, Stephen Diah Iskandar, Cresentia Irene, Rendi Prawira Gunawan, Reganedgary Jonlean and Grace Erdiana

Thalass. Rep. 2026, 16(1), 1; https://doi.org/10.3390/thalassrep16010001 - 19 Dec 2025

Abstract

Background/Objectives: Thalassemia is highly prevalent in Indonesia, and its treatment imposes a significant financial burden. To date, thalassemia management in Indonesia remains largely limited to supportive therapies. This report aims to present the monitoring of the first Indonesian pediatric thalassemia patient to [...] Read more.

Background/Objectives: Thalassemia is highly prevalent in Indonesia, and its treatment imposes a significant financial burden. To date, thalassemia management in Indonesia remains largely limited to supportive therapies. This report aims to present the monitoring of the first Indonesian pediatric thalassemia patient to undergo gene therapy. Methods: Medical summaries were gathered across multiple time points. The gene therapy process consisted of several phases: screening, apheresis and cell manufacturing, conditioning, cell infusion, and post-treatment follow-up. The therapy utilized autologous CD34+ hematopoietic stem and progenitor cells (HSPCs), which were genetically modified using a lentiviral vector carrying the beta-globin gene. The primary outcome of this study was transfusion independence, determined through serial assessments of hematological parameters over a six-month period following gene therapy. Results: A 15-year-old female had been diagnosed with thalassemia major at the age of five. DNA analysis revealed compound heterozygous mutations Hb Malay (codon 19, AAC^Asn > AGC^Ser) and IVS1-nt5 (G > C). She had been receiving regular blood transfusions every 3–4 weeks, and hemosiderosis was detected in the liver and pancreas. Given the patient’s age—over 10 years—hematopoietic stem cell transplantation carries increased risks, making gene therapy the most suitable curative option. During the six-month follow-up period after gene therapy, the patient remained transfusion-independent and experienced no complications. Conclusions: In selecting an appropriate curative therapy for thalassemia patients, several factors must be considered. The successful implementation of the first gene therapy in an Indonesian pediatric thalassemia patient should serve as a catalyst for the continued development and expansion of curative treatment options for thalassemia patients across the country. Full article

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18 pages, 410 KB

Open AccessArticle

Epidemiological and Clinical Profile of Hemoglobinopathies and Thalassemia in Duhok, Kurdistan Region of Iraq: A Retrospective Study

by Burhan Abdullah Zaman, Zuhair Rushdi Mustafa, Delshad Abdulah Mohamed, Hasan Abdullah Aswad and Deldar Morad Abdulah

Thalass. Rep. 2025, 15(4), 12; https://doi.org/10.3390/thalassrep15040012 - 28 Nov 2025

Abstract

Background/Objectives: Thalassemia is among the most common hereditary disorders globally, characterized by impaired hemoglobin synthesis and ineffective erythropoiesis. This study analyzed data on hemoglobinopathies, with a particular focus on thalassemia, to support the development of a comprehensive national database and to improve understanding [...] Read more.

Background/Objectives: Thalassemia is among the most common hereditary disorders globally, characterized by impaired hemoglobin synthesis and ineffective erythropoiesis. This study analyzed data on hemoglobinopathies, with a particular focus on thalassemia, to support the development of a comprehensive national database and to improve understanding of the disease burden in the Kurdistan Region of Iraq. Methods: In this retrospective cross-sectional study, a total of 910 patients admitted to the region’s sole blood disorder center since its establishment were included. Results: The study analyzed 46.7% male and 53.3% female thalassemia patients in Duhok, with 58.46% reporting parental consanguinity. Hepatitis C virus (HCV) prevalence was 11.87%, while 8.90% underwent bone marrow transplantation (BMT) and 30.11% had splenectomies. Blood group distribution was O⁺ (36.26%), A⁺ (30.99%), and B⁺ (18.46%). Common medications included Deferasirox (34.62%), Hydroxyurea (26.70%), and Deferoxamine (5.82%), with 8.24% and 4.40% discontinuing Deferasirox and Hydroxyurea, respectively. Geographically, 29% of the patients originated from Duhok City, which exhibited a consanguinity rate of 18.65% (p = 0.020). The most prevalent conditions were β-thalassemia major (32.53%) and sickle cell anemia (24.73%). HCV-positive patients were predominantly diagnosed with β-thalassemia major (43.40%) and sickle cell anemia (33.96%). BMT recipients were mostly β-thalassemia major patients (80.25%), while splenectomy was common in β-thalassemia major (43.40%) and sickle cell β-thalassemia (22.64%). Vaccination rates included Pneumococcal (50.78%), Influenza (47.76%), and Hepatitis (39.08%, first dose). Six patients (0.66%) died, with 30.18% diagnosed before age 1 and 43.89% between 1 and 2 years. In conclusion, this study underscores the high prevalence of β-thalassemia major and sickle cell anemia in Duhok, with strong associations to parental consanguinity and low socioeconomic status. Gaps in early diagnosis and vaccination coverage remain significant challenges. Full article

(This article belongs to the Section Quality of Life)

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13 pages, 3457 KB

Open AccessArticle

Temporal Changes in Quality of Life and Psychological Burden of Patients with Thalassemia: A Comparative Data Analysis from 2018 to 2025

by Nikos Rikos, Marilena Tzagkaraki, Antigoni Linardaki, Maria Moloudaki and Manolis Linardakis

Thalass. Rep. 2025, 15(4), 11; https://doi.org/10.3390/thalassrep15040011 - 6 Nov 2025

Abstract

Background/Objectives: Thalassemia significantly affects the mental well-being and lifestyle of patients and their families. This study evaluated the temporal changes in quality of life (QoL) and psychological burden among thalassemia patients in 2025 and in relation to 2018. Methods: Two cross-sectional samples of [...] Read more.

Background/Objectives: Thalassemia significantly affects the mental well-being and lifestyle of patients and their families. This study evaluated the temporal changes in quality of life (QoL) and psychological burden among thalassemia patients in 2025 and in relation to 2018. Methods: Two cross-sectional samples of patients (n = 236) were recruited during 2025 (n₁ = 117) and 2018 (n₂ = 119) at the Thalassemia Units on Crete/Greece. The EQ-5D-3L Quality of Life Scale, the EQ VAS Index, and the Hospital Anxiety and Depression Scale (HADS) were used through multiple logistic regression analysis to assess relative parameters. Results: High mean Health Status (EQ VAS Index) and QoL scores remained consistent from 2018 to 2025, anxiety mean levels were low and remained consistent from 2018 to 2025, depression levels were low but higher in 2025 in relation to 2018 (p = 0.041), anxiety significantly exceeded depression in both 2018 and 2025, better QoL was associated with improved health status and reduced anxiety and depression, and individuals with children exhibited significantly lower odds of experiencing low or moderate QoL. Conversely, each unit increase in the Anxiety score significantly increased the odds of low or moderate QoL (OR = 1.26, p = 0.002). Similarly, each unit improvement in health status significantly reduced the odds of low or moderate QoL (OR = 0.97, p = 0.009). Conclusions: Health status and QoL remained consistent from 2018 to 2025, while depression levels increased. Anxiety significantly exceeded depression, and better QoL was associated with improved health status and reduced anxiety and depression. Full article

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16 pages, 716 KB

Open AccessReview

The Interplay Between β-Thalassemia and the Human Virome: Immune Dysregulation, Viral Reactivation, and Clinical Implications

by Didar Hossain and Mohammad Jakir Hosen

Thalass. Rep. 2025, 15(4), 10; https://doi.org/10.3390/thalassrep15040010 - 3 Oct 2025

Abstract

β-thalassemia is a chronic genetic blood disorder characterized by defective β-globin synthesis, requiring frequent transfusions and resulting in iron overload, immune dysfunction, and increased susceptibility to infections. In these immunocompromised patients, altered immune responses lead to significant changes in the human virome, promoting [...] Read more.

β-thalassemia is a chronic genetic blood disorder characterized by defective β-globin synthesis, requiring frequent transfusions and resulting in iron overload, immune dysfunction, and increased susceptibility to infections. In these immunocompromised patients, altered immune responses lead to significant changes in the human virome, promoting viral persistence, reactivation, and expansion of pathogenic viral communities. This review explores the intricate relationship between β-thalassemia and the human virome, focusing on how clinical interventions and immune abnormalities reshape viral dynamics, persistence, and pathogenicity. Patients with β-thalassemia exhibit profound innate and adaptive immune dysregulation, including neutrophil dysfunction, T cell senescence, impaired B cell and NK cell activity, and expansion of myeloid-derived suppressor cells. These alterations create an immunological niche that favors viral reactivation and virome expansion. Iron overload enhances viral replication, while chronic transfusions introduce transfusion-transmitted viruses. Splenectomy and allo-HSCT further compromise viral surveillance. Additionally, disruptions in the gut virome, particularly bacteriophage-driven dysbiosis, may exacerbate inflammation and impair host–virus homeostasis. The human virome is not a passive bystander but a dynamic player in the pathophysiology of β-thalassemia. Understanding virome–immune interactions may offer novel insights for infection monitoring, risk stratification, and precision therapies in thalassemic patients. Full article

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10 pages, 919 KB

Open AccessArticle

Comparing Spectrophotometric Hemoglobin Concentrations with Conventional Laboratory Cell Analyzers in Transfusion-Dependent Beta-Thalassemia Patients

by Khaled Yassen, Nawal Omar, Abdulaziz Bushehab, Renad AlSubaie, Lina AlMudayris, Sara A. Albunyan, Shaima AlAkroush, Sherif Saleh, Dur I. Shahwar and Ossama Zakaria

Thalass. Rep. 2025, 15(3), 9; https://doi.org/10.3390/thalassrep15030009 - 10 Sep 2025

Abstract

Background/Objectives: Thalassemias, a hereditary condition commonly linked to chronic anemia, require regular blood transfusions and repeated blood draws for assessments of hemoglobin (Hb) content, which can be uncomfortable. A promising substitute for laboratory hemoglobin testing is non-invasive spectrophotometric hemoglobin (SpHb) monitoring; however, its [...] Read more.

Background/Objectives: Thalassemias, a hereditary condition commonly linked to chronic anemia, require regular blood transfusions and repeated blood draws for assessments of hemoglobin (Hb) content, which can be uncomfortable. A promising substitute for laboratory hemoglobin testing is non-invasive spectrophotometric hemoglobin (SpHb) monitoring; however, its applicability particularly among blood transfusion-dependent thalassaemic patients needs to be investigated. This study’s primary goal was to investigate the relationships and agreements between SpHb, g/dL, and an automated hematology analyzer (Hb, g/dL) in this particular patient population. The secondary goal was to track how blood transfusions affect SpHb, g/dL, laboratory Hb, and pleth variability index (PVI, %). Methods: In this study, sixty patients were included. A Masimo Radical-7 pulse CO-oximeter was used to measure the SpHb, and a Sysmex XN-1000 hematological analyzer measured the laboratory Hb. Results: The results revealed a significant correlation between SpHb and laboratory Hb (n = 108, r = 0.587, p < 0.001) but also demonstrated that SpHb consistently overestimated laboratory Hb levels, with a mean bias of −1.18 g/dL (95% CI: −1.4344 to −0.9267). The Bland–Altman analysis showed a good degree of reliability between this bias (SpHb–Hb) and laboratory Hb (g/dL), with an Intra Class Correlation (ICC) of 0.613 but with a wide 95% CI ranging from 0.557 to 0.736 (t = 3.817, p < 0.001). The 95% limits of agreement ranged from −3.7893 to +1.4228 g/dL. Conclusions: This significant bias restricted the application of SpHb as a trustworthy method for assessing hemoglobin levels in patients with blood transfusion-dependent thalassemia. Nonetheless, the capability to monitor SpHb and PVI variations during blood transfusions offered a real-time assessment of the impact of transfusions on patients’ hemoglobin levels and volume status. Full article

(This article belongs to the Section Quality of Life)

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8 pages, 216 KB

Open AccessArticle

The Distribution of HLA Alleles in Patients with Beta Thalassemia

by Yasin Yilmaz, Zeynep Karakas, Ayse Erol Bozkurt, Demet Kivanc, Mediha Suleymanoglu, Hayriye Senturk Ciftci, Cigdem Kekik Cinar and Fatma Savran Oguz

Thalass. Rep. 2025, 15(3), 8; https://doi.org/10.3390/thalassrep15030008 - 27 Aug 2025

Abstract

Background: It has been shown that human leucocyte antigen (HLA) alleles are related to certain diseases. Some alleles were associated with alloimmunization in individuals with thalassemia. In this study, we studied the distribution of HLA alleles among beta thalassemia (BT) patients compared to [...] Read more.

Background: It has been shown that human leucocyte antigen (HLA) alleles are related to certain diseases. Some alleles were associated with alloimmunization in individuals with thalassemia. In this study, we studied the distribution of HLA alleles among beta thalassemia (BT) patients compared to healthy controls. Material and Methods: The HLA results of 100 patients with BT and 100 healthy controls were obtained for the study. The HLA-A, -B and -DRB1 tissue typing were performed at the laboratory. The low-resolution sequence-specific primer (SSP)–polymerase chain reaction (PCR-SSP) (Olerup HLA-A,B,DR typing kit, USA) and sequence-specific oligonucleotide (SSO)–PCR (LABType HLA-A,B,DR kit, ABD) methods were performed using the Luminex genotyping kits. All related data were retrospectively analyzed. Results: One in five patients (21%) underwent hematopoietic stem cell transplantation (HSCT). Patients with HSCT had significantly lower frequency of HLA-B *14, HLA-DRB1 *11 and HLA-DRB1 *16 alleles and had a higher frequency of HLA-A *66, HLA-B *41, HLA-B *55, HLA-DRB1 *3 alleles compared to patients without HSCT (p < 0.05). The HLA-A *3, HLA-B *41 and HLA-B *55 alleles were more commonly seen in HSCT patients compared to the healthy group (p = 0.04). Female patients showed a higher frequency of HLA-B *58 and HLA-DRB1 *4 alleles (p = 0.04). Conclusions: This study demonstrated that HLA-B *41 and -B *55 alleles were closely related to HSCT among BT patients. It might be considered that the variance in certain HLA-B alleles in BT patients might cause difficulty in finding a matched donor in this limited population. Full article

(This article belongs to the Section Innovative Treatment of Thalassemia)

21 pages, 3070 KB

Open AccessSystematic Review

Curcumin Therapy Reduces Iron Overload and Oxidative Stress in Beta-Thalassemia: Findings from a Meta-Analytic Study

by Kabelo Mokgalaboni, Wendy N. Phoswa, Perpetua Modjadji and Sogolo L. Lebelo

Thalass. Rep. 2025, 15(3), 7; https://doi.org/10.3390/thalassrep15030007 - 2 Jul 2025

Cited by 3

Abstract

The risk of anemia and iron overload is a global concern in beta (β)-thalassemia. The β-thalassemia primary treatment includes blood transfusion and iron chelation therapy; however, both are associated with risks such as anemia, iron depletion, overload, and oxidative stress if not adequately [...] Read more.

The risk of anemia and iron overload is a global concern in beta (β)-thalassemia. The β-thalassemia primary treatment includes blood transfusion and iron chelation therapy; however, both are associated with risks such as anemia, iron depletion, overload, and oxidative stress if not adequately monitored. Therefore, this study investigates the effects of curcumin on anemia, iron overload, and oxidative stress in β-thalassemia. In this meta-analysis, search terms including “curcumin,” “Curcuma longa,” “curcuminoids,” “turmeric,” and “thalassemia” were used in Scopus and PubMed to identify studies published from inception to 15 February 2025. The quantitative analysis was performed using a meta-analysis web tool, and the effect estimates were reported as the mean difference (MD) or standardized mean difference (SMD), along with 95% confidence intervals (CI). Our analysis showed no significant effect on hemoglobin (p = 0.1788) and red blood cell count (p = 0.9534). In contrast, there was a significant decrease in serum ferritin [SMD = −0.24 (−0.46, −0.02), p = 0.0335], non–transferrin bound iron (NTBI), [SMD = −0.59 (−0.98, −0.19), p = 0.0039] and serum iron, [SMD = −0.30 (−0.60, −0.01), p = 0.0425]. Furthermore, there was a reduction in reactive oxygen species; [SMD = −0.83 (−1.23, −0.44), p < 0.0001] and malonaldehydes, [MD = −343.85 nmol/g Hb (−465.94, −221.76), p < 0.0001]. A dose of 500 mg of curcumin was found to be more effective in reducing the NTBI. The findings suggest that curcumin may help reduce iron overload and oxidative stress in β-thalassemia; however, its effect on improving anemia appears to be limited. Given the small sample size of the included studies, we recommend that future research involve larger cohorts and employ rigorous methodologies to evaluate the therapeutic potential of curcumin in β-thalassemia thoroughly. Additionally, we recommend using curcumin-enhancing strategies to improve its bioavailability and administer an optimal yet effective dose. Full article

(This article belongs to the Special Issue Innovative Therapies and Management of Complications in Hemoglobinopathies)

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12 pages, 722 KB

Open AccessCase Report

A Rare Case of High Physical Endurance in Transfusion-Dependent Thalassemia Patients with Poor Cardiac Functions

by Nathasha Brigitta Selene, Ayudra Fitrananda, Natasha Yemima Situmorang, Kamilia Rifani Ufairah, Stephen Diah Iskandar and Pustika Amalia Wahidiyat

Thalass. Rep. 2025, 15(2), 6; https://doi.org/10.3390/thalassrep15020006 - 9 Jun 2025

Abstract

Background/Objectives: Chronic anemia and iron overload in thalassemia lead to organ failures, including the heart, liver, endocrine glands, and spleen. Comprehensive multidisciplinary management is pivotal in improving patients’ clinical outcomes and well-being. The report aims to present a rare case of improved [...] Read more.

Background/Objectives: Chronic anemia and iron overload in thalassemia lead to organ failures, including the heart, liver, endocrine glands, and spleen. Comprehensive multidisciplinary management is pivotal in improving patients’ clinical outcomes and well-being. The report aims to present a rare case of improved clinical condition in a transfusion-dependent thalassemia patient. Methods: Medical summaries were collected to compare patients’ conditions at various time frames. Furthermore, the report was composed in chronological order. Results: A 31-year-old male diagnosed with beta-thalassemia major and multiple comorbidities, including diabetes with a history of diabetic ketoacidosis, heart failure with a history of cardiac arrest, hepatomegaly, severe thoracolumbar scoliosis, and depression, exhibited a high physical endurance. The patient managed to maintain a strong treatment adherence and undergo intensive regular multidisciplinary follow-ups. The patient gained cardiac function improvement and metabolic stabilization, leading to completing a 5 k marathon without complication. Conclusions: Intensive management of iron overload through double oral chelation allows organ function improvement. Better mental health attenuates the patient’s overall well-being and is attributed to the ability to gain high physical endurance. Full article

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10 pages, 222 KB

Open AccessEditor’s ChoiceArticle

Prevalence and Specificity of Red Blood Cell Alloimmunization: Insights from Transfusion-Dependent Populations in Serbia

by Radovan Dinić, Nevenka Bujandrić and Jasmina Grujić

Thalass. Rep. 2025, 15(2), 5; https://doi.org/10.3390/thalassrep15020005 - 7 May 2025

Cited by 1

Abstract

Background/Objectives: Red blood cell (RBC) alloimmunization is a significant challenge in transfusion medicine, particularly among transfusion-dependent patients, such as those with thalassemia. It arises from the production of antibodies against non-self RBC antigens and can lead to complications like hemolytic transfusion reactions. This [...] Read more.

Background/Objectives: Red blood cell (RBC) alloimmunization is a significant challenge in transfusion medicine, particularly among transfusion-dependent patients, such as those with thalassemia. It arises from the production of antibodies against non-self RBC antigens and can lead to complications like hemolytic transfusion reactions. This study aimed to evaluate the prevalence, specificity, and clinical implications of RBC alloimmunization at the University Clinical Center of Serbia (UCCS), emphasizing transfusion-dependent populations. Methods: This retrospective study analyzed 27,530 transfusion records at UCCS between January 2023 and January 2024. Pre-transfusion testing included ABO and RhD typing, irregular antibody screening, and crossmatching. Data from 630 patients with positive antibody screening were reviewed. Alloantibody specificity was determined using indirect antiglobulin tests and advanced phenotyping methods. Results: Among 27,530 patients, 630 (2.29%) tested positive for irregular antibodies, predominantly males (57.14%) with a mean age of 49.6 years. Alloantibodies were detected in 70.47% of cases, most commonly targeting Rh (53.35%) and Kell (17.15%) systems. Anti-E (27.93%) and anti-D (18.02%) were the most frequent antibodies. Multiple alloantibodies were identified in 18.41% of patients, posing challenges for blood compatibility. In a total of 495 patients with thalassemia, antibodies were found in 9.69%. Alloimmunization was significantly associated with higher numbers of transfusions and pregnancies (p < 0.05). Conclusions: Our findings indicate that alloimmunization is predominantly associated with Rh and Kell antigens, suggesting that implementing targeted antigen matching may reduce the frequency of alloimmunization. While our study does not directly assess the impact of genotypic matching, the prior literature supports its role in enhancing transfusion safety, particularly for high-risk populations like thalassemia patients. Full article

9 pages, 727 KB

Open AccessEditor’s ChoiceArticle

Dysregulation of Iron Homeostasis in β-Thalassemia and Impaired Neutrophil Activity

by Sreenithi Santhakumar, Leo Stephen, Aruna Barade, Uday Kulkarni, Biju George and Eunice S. Edison

Thalass. Rep. 2025, 15(2), 4; https://doi.org/10.3390/thalassrep15020004 - 25 Apr 2025

Cited by 2

Abstract

Background/Objective: Patients with beta-thalassemia are more susceptible to iron overload and have altered neutrophil function. This study investigated the connections between iron metabolism in neutrophils, neutrophil functionality, and overall iron status in individuals with β-thalassemia and sickle cell anemia. Methods: We recruited [...] Read more.

Background/Objective: Patients with beta-thalassemia are more susceptible to iron overload and have altered neutrophil function. This study investigated the connections between iron metabolism in neutrophils, neutrophil functionality, and overall iron status in individuals with β-thalassemia and sickle cell anemia. Methods: We recruited 18 patients with β-thalassemia, 5 patients with sickle cell anemia, and 15 healthy controls. Our evaluation included measurements of iron and hepcidin concentrations in the serum, along with an analysis of neutrophil function, specifically their phagocytic and oxidative burst capabilities. In addition, we examined the expression of iron transport proteins in neutrophils. Results: Patients with β-thalassemia showed significant iron overload, reduced neutrophil counts, and decreased oxidative burst activity and phagocytosis. Systemic iron status is inversely correlated with the phagocytic capacity of β-thalassemia neutrophils. Regression analysis indicated a significant association between serum iron level, transferrin iron binding capacity, transferrin saturation, and neutrophil percentage. These findings elucidate the essential role of systemic iron levels in neutrophil efficacy against infections. Furthermore, FPN1B and DMT1A mRNA levels were upregulated, and IRP2 was downregulated in the neutrophils of patients with β-thalassemia major and intermedia compared to controls. Conclusions: Elevated systemic iron levels were associated with reduced neutrophil counts and impaired neutrophil function in patients with β-thalassemia. These findings highlight a critical role of systemic iron overload in neutrophil dysfunction. Full article

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6 pages, 197 KB

Open AccessPerspective

The Changing Landscape of Opportunity for Cure of Severe Hemoglobinopathies in Middle-Income Regions

by Lawrence Faulkner

Thalass. Rep. 2025, 15(1), 3; https://doi.org/10.3390/thalassrep15010003 - 6 Mar 2025

Cited by 1

Abstract

Thalassemia and sickle cell disease remain the most common life-threatening non-communicable diseases in children worldwide and an increasing burden on affected families and health services. Significant progress has been made in terms of technologies to improve access to a cure by both allogeneic [...] Read more.

Thalassemia and sickle cell disease remain the most common life-threatening non-communicable diseases in children worldwide and an increasing burden on affected families and health services. Significant progress has been made in terms of technologies to improve access to a cure by both allogeneic and autologous gene-modified hematopoietic stem cell transplantation (HSCT). However, the high cost of cutting-edge treatments often places them beyond the reach of individual families or even national healthcare systems. Advances in frugal innovation and simplified HSCT procedures for low-risk transplants have significantly reduced the costs and complexities associated with HSCT without compromising on quality and outcomes. Because of the geographical distribution of hemoglobinopathies, i.e., largely in low- and middle-income countries (LMICs), HSCT cost optimization has the potential to impact a huge number of patients, increasing hope for a cure and health-related quality of life normalization, which in turn may affect supportive care compliance. Furthermore, because of the high burden of disease, LMIC transplant centers are rapidly increasing in number and developing unique expertise for the cure of thalassemia and sickle cell disease, particularly in India, where the Sankalp India Foundation with the support of DKMS and Cure2Children has implemented several cost-conscious transplant services. In fact, the very high success rate, increasing cost-effectiveness of transplantation, as well as the chronic nature of these conditions make them ideal initial candidates for start-up transplant centers, so it is likely that the global capacity for a cure for severe hemoglobinopathies will substantially increase in the years to come. Full article

(This article belongs to the Section Conventional Treatment of Thalassemia)

10 pages, 487 KB

Open AccessEditor’s ChoiceReview

New Perspectives on the Impact of Iron Chelation Therapy on the Gut Microbiome in Thalassemia Patients

by Sara Deumić, Neira Crnčević, Mirsada Hukić, Muamer Dizdar and Monia Avdić

Thalass. Rep. 2025, 15(1), 2; https://doi.org/10.3390/thalassrep15010002 - 10 Feb 2025

Cited by 1

Abstract

Thalassemia, a genetic condition characterized by defective hemoglobin synthesis, is often managed with transfusion therapy, which can lead to iron overload—a significant contributor to morbidity and mortality due to organ damage and pathogenic infections. Iron chelation therapy, the cornerstone of managing iron toxicity, [...] Read more.

Thalassemia, a genetic condition characterized by defective hemoglobin synthesis, is often managed with transfusion therapy, which can lead to iron overload—a significant contributor to morbidity and mortality due to organ damage and pathogenic infections. Iron chelation therapy, the cornerstone of managing iron toxicity, may inadvertently influence the gut microbiome, a critical modulator of immunity and metabolism. This review provides new insights into the interplay between iron chelation therapy and gut microbiome dynamics in thalassemia patients. It synthesizes findings on how chelators such as deferoxamine, deferasirox, and deferiprone influence microbial composition, iron availability, and systemic inflammation. Emerging evidence highlights alterations in gut microbial diversity, with reduced beneficial taxa and increased pathogenic populations, driven by changes in luminal iron levels. This imbalance contributes to immune dysregulation, systemic inflammation, and susceptibility to infections. The review advocates for tailored treatment strategies that integrate microbiome-targeted interventions alongside traditional chelation therapy to improve patient outcomes. By combining genetic profiling, dietary adjustments, and microbiome modulation, this approach offers a promising avenue for personalized medicine in thalassemia care. Full article

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