Journal Description

Thalassemia Reports

Thalassemia Reports is an international, peer-reviewed, open access journal on the study, diagnosis, and treatment of thalassemia, published quarterly online by MDPI (from Volume 12 Issue 1-2022).

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within ESCI (Web of Science), and other databases.
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 31.7 days after submission; acceptance to publication is undertaken in 5.3 days (median values for papers published in this journal in the first half of 2023).
Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.

Impact Factor: 0.3 (2022)

Imprint Information Journal Flyer Open Access ISSN: 2039-4365

Latest Articles

11 pages, 297 KiB

Open AccessArticle

Association of Bone Disorder and Gene Polymorphism of PPAR-γ Pro12 Ala in Egyptian Children with β-Thalassemia

Ahmed M. Abdel Hamied

Heba Mostafa Ahmed

Dina H. Eldahshan

Dalia S. Morgan

Abdel Meged A. Abdel Meged

and

Thalass. Rep. 2023, 13(4), 230-240; https://doi.org/10.3390/thalassrep13040020 - 30 Sep 2023

Abstract

β-thalassemia is a genetic disorder affecting chromosome 16, inherited from one or both parents. In spite of the improved treatment of the hematological disorder and its complications, β-thalassemic patients still exhibit an imbalance in bone mineral turnover, resulting in diminished bone mineral density (BMD), more evident in the lumbar spine. The purpose of this study was to investigate the association between genetic polymorphism of the PPAR-γ gene and the presence of osteopenia or osteoporosis in children with β-thalassemia. This case–control study was conducted on 50 children with β-thalassemia from the pediatric hematology unit of Beni-Suef University Hospital, including 50 healthy children as the control group. The age range was 8 to 18 years. Samples of patients and control subjects were analyzed for the presence of polymorphisms of the PPAR-γ gene and other blood labs. An assay of BMD measure using dual-energy X-ray absorptiometry (DXA) was performed to investigate osteopenia or osteoporosis. Statistical analysis was used to investigate the relationship between the risk of osteopenia or osteoporosis and the presence of PPAR-γ Pro12Ala gene polymorphism. Eighteen (eleven males and seven females) of fifty patients (representing 36% of the patients group) have osteopenia with low bone mineral density (Z-score is −1 or less than 1). There was no statistically significant difference between BMD measurements in males and females. By comparing the frequency of 12 Ala gene polymorphisms between the patient group and the control group, we found that no statistically significant difference was detected. The BMD values were not significantly different between the groups of PPAR-γ Pro12Ala gene polymorphism. In conclusion, decreased BMD levels are frequent in β-thalassemia patients. PPAR-γ Pro12Ala gene polymorphism is not common in Egyptian patients with β-thalassemia. No significant relationship was found between the PPAR-γ Pro12Ala gene polymorphism and low BMD levels or osteopenia in Egyptian β-thalassemia patients. However, further studies on a larger population of Egyptian patients are needed to confirm this finding. Full article

24 pages, 1682 KiB

Open AccessReview

Infection and Potential Challenge of Childhood Mortality in Sickle Cell Disease: A Comprehensive Review of the Literature from a Global Perspective

and

Pasupuleti Visweswara Rao

Thalass. Rep. 2023, 13(3), 206-229; https://doi.org/10.3390/thalassrep13030019 - 30 Aug 2023

Abstract

Sickle cell disease (SCD) is a complex genetic disorder associated with multiple clinical manifestations, including increased susceptibility to bacterial and viral infections. This review article presents a comprehensive analysis of the current literature obtained from various online databases focusing on the relationship between SCD and infections caused by specific pathogens, such as pneumonia- and influenza-causing pathogens, Escherichia coli, Staphylococcus aureus, parvovirus, and hepatitis viruses. We discuss the underlying mechanisms that contribute to the increased susceptibility of individuals with SCD to these infections, primarily related to the pathophysiology of variant hemoglobin (HbSS) and its impact on vascular occlusion, hemolysis, functional asplenia, and immune deficiency. Moreover, we highlight the significant burden of infections on SCD patients, particularly children under five years of age, where they are the leading cause of morbidity and mortality. Additionally, we address the challenges faced in attempts for reducing the global mortality rate associated with SCD, particularly in low-income countries, where factors such as increased pathogen exposure, co-morbidities like malnutrition, lower vaccination rates, and limited healthcare facilities contribute to the high disease burden. This review emphasizes the need for targeted interventions, improved healthcare access, vaccination programs, and infection prevention strategies to alleviate the impact of infections on individuals with SCD and reduce the global mortality rates associated with the disease. Full article

(This article belongs to the Section Quality of Life)

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11 pages, 2659 KiB

Open AccessReview

Association between Glomerular Filtration Rate and β-Thalassemia Major: A Systematic Review and Meta-Analysis

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Thalass. Rep. 2023, 13(3), 195-205; https://doi.org/10.3390/thalassrep13030018 - 29 Aug 2023

Abstract

Thalassemia is one of the most prevalent genetic disorders worldwide and has previously been found to have an association with several physiological and organ complications. Several studies have found both its positive and inverse correlation with the glomerular filtration rate (GFR). Therefore, in this meta-analysis, we tried to assess the accurate correlation of β-thalassemia major (β-TM) with GFR. We searched in Google Scholar, PubMed, and ScienceDirect, and from the initial 96 articles, we finally included 12 studies. The quality and publication bias assessment confirmed that all the studies were of high to moderate quality with no publication bias. The main outcome of the mean difference (MD) was −6.94, 95%CI: −20.69, 6.80 (p < 0.00001), which indicated a negative correlation of the GFR with β-TM. The sensitivity analyses found one study to be a slight outlier, and reanalyzing the data excluding that study, an MD was achieved of −16.46, 95%CI: −26.81, −6.11 (p < 0.00001), which provides even stronger support for our main outcome. Our result determined that the GFR is generally higher in healthy people as compared to β-TM patients. Full article

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16 pages, 1005 KiB

Open AccessReview

Understanding the Intricacies of Iron Overload Associated with β-Thalassemia: A Comprehensive Review

Subhangi Basu

Motiur Rahaman

Tuphan Kanti Dolai

Praphulla Chandra Shukla

and

Nishant Chakravorty

Thalass. Rep. 2023, 13(3), 179-194; https://doi.org/10.3390/thalassrep13030017 - 03 Jul 2023

Abstract

β-thalassemia, a congenital genetic hematological disorder characterized by the decrease or absence of β-globin chains, leads to a decrease in levels of Hemoglobin A. The affected individuals can be categorized into two cohorts based on transfusion dependency: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). Remarkably, despite the primary pathology lying in β-globin chain depletion, β-thalassemia also exhibits an intriguing association with iron overload. Iron metabolism, a tightly regulated physiological process, reveals a complex interplay in these patients. Over time, both cohorts of β-thalassemic individuals develop iron overload, albeit through distinct mechanisms. Addressing the diverse complications that arise due to iron overload in β-thalassemic patients, the utilization of iron chelators has gained a lot of significance. With varying efficacies, routes of administration, and modes of action, different iron chelators offer unique benefits to patients. In the Indian context, three commercialized iron chelators have emerged, showcasing a high adherence rate to iron chelator-based treatment regimens among β-thalassemic individuals. In this review, we explore the intriguing connection between β-thalassemia and iron overload, shedding light on the intricate mechanisms at play. We delve into the intricacies of iron metabolism, unveiling the distinct pathways leading to iron accumulation in these patients. Additionally, the therapeutic efficacy of different iron chelators in managing iron overload complications is mentioned briefly, along with the guidelines for their usage in India. Through this comprehensive analysis, we aim to deepen our understanding of β-thalassemia and iron overload, paving the way for optimized treatment strategies. Ultimately, our findings provide valuable insights into improving the care and outcomes of individuals affected by β-thalassemia. Full article

(This article belongs to the Special Issue Thalassemia Syndromes in Developing Countries: Has Anything Changed?)

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14 pages, 1738 KiB

Open AccessArticle

Molecular Epidemiology of HCV Infection among Multi-Transfused β-Thalassemia Patients in Eastern India: A Six-Year Observation

Maitreyee Bhattacharyya

Sharmistha Chakraborty

Shanta Dutta

and

Provash Chandra Sadhukhan

Thalass. Rep. 2023, 13(3), 165-178; https://doi.org/10.3390/thalassrep13030016 - 25 Jun 2023

Abstract

Background: HCV infection is very common in multi-transfused β-thalassemia patients who need regular blood transfusions. Aim: The study was conducted to determine the epidemiology of HCV in multi-transfused β-thalassemia patients in West Bengal, India. Methods: Over a span of six years, blood samples were collected from HCV sero-reactive β-thalassemia patients and processed for viral RNA isolation followed by nested RT-PCR for qualitative viremia detection. The HCV genotype was determined by amplifying the partial HCV core gene by nested RT-PCR followed by DNA sequencing and NCBI genotyping tools. Phylogenetic and phylogeographic studies were performed with MEGA-X and BEAST software, respectively. Results: Out of 917 multi-transfused HCV sero-reactive β-thalassemia patients, 598 (65.21%) were HCV RNA positive while 250 (41.80%) had spontaneously cleared the virus. A significant percentage of male patients from rural areas (p = 0.042) and economically backward class (p = 0.002) were at higher risk of HCV infection. Female thalassemia patients and individuals belonging to ages 11–15 years had higher chances of spontaneous clearance. The most prevalent circulatory HCV genotype was 3a (78.26%) followed by 1b (12.04%). Phylogeographic analyses revealed that the 3a strains share genomic similarities with strains from Pakistan, Sri Lanka, and Thailand, whereas the 1b strains share similarities with strains from Thailand, Vietnam, Russia, and China. Uncommon HCV subtypes 3g and 3i were also detected. Conclusion: The high prevalence of HCV infection among β-thalassemia patients of West Bengal, India indicates NAT-based assays should be implemented for HCV screening in donor blood to eliminate HCV by 2030. Full article

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8 pages, 789 KiB

Open AccessReview

The Benign Clone Causing Aplastic Anaemia

Shaun R. McCann

and

Andrea Piccin

Thalass. Rep. 2023, 13(2), 157-164; https://doi.org/10.3390/thalassrep13020015 - 12 Jun 2023

Abstract

Severe Aplastic Anaemia (SAA) is a rare benign disease but carries a high-mortality rate unless treated in a specialised centre. Overwhelming laboratory and clinical evidence points to an autoimmune pathogenesis; although, the aetiology remains obscure in the majority of cases. The differential diagnosis in older patients is problematical and a diagnosis of hypoplastic myelodysplasia remains difficult. This review points out the difficulty in diagnosis without a specific test. Future research needs to define a specific diagnostic test and refine therapeutic interventions. Full article

(This article belongs to the Special Issue Thalassemia Syndromes as a Benign Cancer of Hematopoietic Stem Cells)

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5 pages, 458 KiB

Open AccessCase Report

Hb^Adrian (α1:c.251del, p.Leu84Argfs*19)—A Novel Pathogenic Variant in the α1-Globin Gene Associated with Microcytosis from the North of Iran

Hossein Jalali

Hossein Karami

Mahan Mahdavi

and

Mohammad Reza Mahdavi

Thalass. Rep. 2023, 13(2), 152-156; https://doi.org/10.3390/thalassrep13020014 - 01 Jun 2023

Abstract

Background: Alpha thalassemia is one of the most common human genetic abnormalities. More than 400 different variations of the α-globin protein have been introduced, most of which are not associated with noticeable clinical manifestations. The identification of all variants of Hb in different regions helps in acquiring comprehensive knowledge concerning thalassemia disease, and it can be used in preventive programs as well as prenatal diagnosis (PND). Aims: In the present study, we describe a new α1 gene mutation that leads to a frameshift after codon 83. Methods: As a plan for a national screening program of thalassemia, routine cell blood count (CBC) and Hb capillary electrophoresis tests were applied. After taking written informed consent, genomic DNA was extracted, and, for identifying common Mediterranean α-Globin gene deletion, multiplex Gap-PCR was performed; for detecting other mutations on α- and β-Globin genes, a DNA sequencing method was used. Results: The results of CBC and capillary electrophoresis tests showed microcytosis in a female subject. The sequencing of the α-Globin gene showed that the case is heterozygote for a single-nucleotide deletion at codon 83 of the α1-Globin Gene. We named this mutation Hb Adrian (α1: c.251–T), which is a novel mutation. The mentioned mutation was also detected in the subject’s mother. Conclusions: The introduced mutation (Hb Adrian) leads to a frameshift change that produces a protein with 100 amino acids, which in comparison to a normal α-chain is shorter, and its amino acids are altered after codon 83. This hemoglobin is undetectable via the use of electrophoresis. Although no major hematological abnormalities were observed in the carriers, Hb Adrian should be considered in screening programs to help prevent Hb H disease in high-risk couples. Full article

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8 pages, 707 KiB

Open AccessPerspective

What Is the Relevance of Murburn Concept in Thalassemia and Respiratory Diseases?

Kelath Murali Manoj

Thalass. Rep. 2023, 13(2), 144-151; https://doi.org/10.3390/thalassrep13020013 - 12 May 2023

Abstract

Murburn concept is a novel perspective for understanding cellular function, deeming cells as simple chemical engines (SCE) that are powered by redox reactions initiated by effective charge separation (ECS). The 1-electron active diffusible reactive (oxygen) species, or DR(O)S, equilibriums involved in these processes are also crucial for homeostasis, coherently networking cells, and rendering electromechanical functions of sensing and responding to stimuli. This perspective presents the true physiological function of oxygen, which is to enable ECS and the generation of DR(O)S. Therefore, DR(O)S must now to be seen as the quintessential elixir of life, although they might have undesired effects (i.e., the traditionally perceived oxidative stress) when present in the wrong amounts, places and times. We also elaborated that tetrameric hemoglobin (Hb) is actually an ATP-synthesizing murzyme (an enzyme working via murburn concept) and postulated that several post-translational modifications (such as glycation) on Hb could result from murburn activity. Murburn perspective has also enabled the establishment of a facile rationale explaining the sustenance of erythrocytes for 3–4 months, despite their lacking nucleus or mitochondria (to coordinate their various functions and mass-produce ATP, respectively). Although thalassemia has its roots in genetic causation, the new awareness of the mechanistic roles of oxygen-hemoglobin-erythrocyte trio significantly impacts our approaches to interpreting research data and devising therapies for this malady. These insights are also relevant in other clinical manifestations that involve respiratory distress (such as asthma, lung cancer, COVID-19 and pneumonia) and mitochondrial diseases. Herein, these contexts and developments are briefly discussed. Full article

(This article belongs to the Special Issue Thalassemia Syndromes in Developing Countries: Has Anything Changed?)

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13 pages, 1385 KiB

Open AccessArticle

Spectrum of Thalassemia and Hemoglobinopathy Using Capillary Zone Electrophoresis: A Facility-Based Single Centred Study at icddr,b in Bangladesh

Anamul Hasan

Jigishu Ahmed

Bikash Chandra Chanda

Maisha Aniqua

Raisa Akther

Palash Kanti Dhar

Kazi Afrin Binta Hasan

and

Thalass. Rep. 2023, 13(2), 131-143; https://doi.org/10.3390/thalassrep13020012 - 10 May 2023

Abstract

Background: Although the global thalassemia zone covers Bangladesh, there are very limited studies conducted in this region. Therefore, the focus of our study is to understand the prevalence and burden of thalassemia and hemoglobinopathy in Bangladesh. Methods: The analysis was based on a retrospective evaluation of laboratory diagnoses between 2007 January and 2021 October. A total of 8503 specimens were sampled and analyzed which were either referred by corresponding physicians or self-referred. This was neither any epidemiological nationwide survey nor was the study population chosen randomly. Hematological data were obtained through capillary zone electrophoresis and corresponding complete blood count. Results: 1971 samples (~23.18% of the total) were found with at least one inherited hemoglobin disorder. The most common hemoglobin disorder observed was the hemoglobin E (Hb E) trait (10.67%), followed by the β-thalassemia trait (8.4%), homozygotic Hb E (1.59%), and Hb E/β-thalassemia (1.58%). Other variants found in this study with minimal percentages were Hb N-Seattle, Hb S, Hb D-Punjab, Hb Lepore, Hb C, Hb Hope, Hb H, and hereditary persistence of fetal hemoglobin. Discussion: The pattern of thalassemia and hemoglobinopathy in our study is diverse and heterogeneous. A broad and detailed spectrum of such inherited hemoglobin disorders will ultimately be helpful in implementing nationwide thalassemia management and strategy policy in Bangladesh. Full article

(This article belongs to the Special Issue Thalassemia Syndromes in Developing Countries: Has Anything Changed?)

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9 pages, 268 KiB

Open AccessFeature PaperReview

Bone Marrow Transplantation in Nonmalignant Haematological Diseases: What Have We Learned about Thalassemia?

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Thalass. Rep. 2023, 13(2), 122-130; https://doi.org/10.3390/thalassrep13020011 - 24 Apr 2023

Abstract

Allogeneic stem cell transplantation remains the only therapy for congenital, severe haemoglobinopathies that is able to reverse the pathological phenotype. In the severe form of thalassemia, regular transfusions are needed early in life. This population of patients could benefit from allo-SCT. However, the great efficacy of transplantation must be counterbalanced by the mortality and morbidity related to the procedure. In this short review, we reviewed the most recent data in the field of transplantation in transfusion-dependent thalassemia (TDT), highlighting the factors that have a major impact on outcomes. Full article

(This article belongs to the Special Issue Thalassemia Syndromes as a Benign Cancer of Hematopoietic Stem Cells)

9 pages, 379 KiB

Open AccessArticle

Effect of HFE Gene Mutations on Iron Metabolism of Beta-Thalassemia Carriers

María E. Mónaco

Natalia S. Alvarez Asensio

Cecilia Haro

Magdalena M. Terán

Miryam E. Ledesma Achem

Blanca A. Issé

and

Sandra S. Lazarte

Thalass. Rep. 2023, 13(1), 113-121; https://doi.org/10.3390/thalassrep13010010 - 17 Mar 2023

Abstract

The human hemochromatosis protein HFE is encoded by the HFE gene and participates in iron regulation. The aim of this study was to detect the most frequent HFE gene mutations in a control population and in β-thalassemia trait (BTT) carriers, and to study their relationship with iron metabolism. Total blood count, hemoglobin electrophoresis at alkaline pH, HbA₂ quantification, iron (Fe), total Fe binding capacity and ferritin were assayed. HFE gene mutations were analyzed by real-time PCR. A total of 119 individuals (69 normal and 50 BTT) were examined. In the control group, 9% (6/69) presented a codon 282 heterozygous mutation (C282Y), and 19% a codon 63 mutation (H63D) (13/69, 11 heterozygotes and 2 homozygotes). In the BTT group, 3 carriers (6%) were heterozygous for C282Y, 14 (28%) for H63D, 1 (2%) for a codon 65 mutation and 1 (2%) was H63D and C282Y double heterozygous. Control group Fe metabolism did not show significant differences (p > 0.05) according to whether or not they carried an HFE gene mutation; while the BTT group with and without HFE mutation showed higher Fe and ferritin than the control group (p < 0.05). However, no increases in iron parameters were detected in BTT carriers that simultaneously exhibited an H63D mutation compared to BTT subjects without a mutation. Therefore, the iron metabolism alterations observed in BTT carriers could not be attributed to the presence of HFE gene mutations. It is likely that BTT individuals have other genetic modifiers that affect their iron balance. Full article

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

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28 pages, 6465 KiB

Open AccessArticle

Impact of Genetic Polymorphisms in Modifier Genes in Determining Fetal Hemoglobin Levels in Beta-Thalassemia

and

Aditya Narayan Sarangi

Thalass. Rep. 2023, 13(1), 85-112; https://doi.org/10.3390/thalassrep13010009 - 16 Mar 2023

Abstract

Genetic polymorphisms in Quantitative Trait Loci (QTL) genes such as BCL11A, HBS1L-MYB and KLF1 have been reported to influence fetal hemoglobin (HbF) levels. This prospective study was planned to evaluate the role of genetic polymorphisms in QTL genes as determinant of HbF levels in beta thalassemia major patients. The study was carried out on 100 thalassemia major patients. Blood samples were collected in EDTA and plain vials for biochemical and molecular evaluation. The BCL11A, HBS1L-MYB and KLF1 genotypes were determined using a polymerase chain reaction (PCR)-based method. Red Blood Cell (RBC) indices and HbF levels were assessed. In silico analysis was assessed using loss-of-function tool (Lof Tool). Statistical difference and genetic comparisons between groups were evaluated by using SPSS for Windows, version 16.0 (SPSS Inc., Chicago, IL, USA). Comparisons between quantitative variables were carried out after data explored for normality using Kolmogorov–Smirnov test of normality. Logistic regression was used for computation of ORs and 95% CIs (Confidence Interval). We observed association of HbF levels in thalassemia major patients with the polymorphisms in BCL11A (rs11886868 rs7557939; rs1427407 and rs766432) and HBS1L-MYB (rs9399137) gene. The results of this study indicated that the presence of polymorphisms on modifier genes are strongly associated with an increase in HbF levels in thalassemia major patients. Further research with a larger sample size and with other genes of modifier genes is required. Full article

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

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8 pages, 619 KiB

Open AccessPerspective

Highlights on the Luspatercept Treatment in Thalassemia

Yesim Aydinok

Thalass. Rep. 2023, 13(1), 77-84; https://doi.org/10.3390/thalassrep13010008 - 20 Feb 2023

Abstract

Luspatercept has been shown to act as a ligand trap, selectively suppressing the deleterious effects of GDF11 that blocks terminal erythroid maturation, restoring normal erythroid differentiation and improving anemia in animal models of β-thalassemia. Effective doses of luspatercept achieved hemoglobin increase within 7 days of the first dose, and plasma half-life supports subcutaneously administration every 21 days in adults with β-thalassemia. A Phase 3, placebo-controlled 1-year study with starting dose of 1.0 up to 1.25 mg/kg every 21 days achieved ≥33% reduction in red cell transfusion volume in 21.4% of adult transfusion-dependent β-, HbE/β-thalassemia patients on luspatercept vs. 4.5% on placebo over a fixed 12-week period, and 41.1% of patients in luspatercept vs. 2.7% placebo in any 24-week period. Luspatercept allowed ≥1.0 and ≥1.5 g/dL increase in hemoglobin from baseline in 77% and 52.1% of adult non-transfusion-dependent β-, HbE/β-thalassemia patients vs. 0% placebo over a 12-week interval. Although not significant, a greater improvement in patient-reported outcomes was observed with luspatercept. Luspatercept had a manageable safety profile with notable adverse effects of venous thromboembolism in 3.6% of transfusion-dependent β-thalassemia vs. 0.9% of placebo and extramedullary hematopoiesis in 6% of non-transfusion-dependent β-thalassemia vs. 2% of placebo. The pediatric study started patients’ enrollment. Full article

(This article belongs to the Special Issue Thalassemia Syndromes as a Benign Cancer of Hematopoietic Stem Cells)

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7 pages, 1237 KiB

Open AccessArticle

New-Generation Ektacytometry Study of Red Blood Cells in Different Hemoglobinopathies and Thalassemia

and

Joan-Lluis Vives-Corrons

Thalass. Rep. 2023, 13(1), 70-76; https://doi.org/10.3390/thalassrep13010007 - 16 Feb 2023

Abstract

Next-generation ektacytometry provided by the osmoscan module of the Laser Optical Rotational Red Cell Analyser (LoRRca) MaxSis is, so far, one of the best complementary diagnostic tools for congenital rare anaemias due to red blood cell defects. Osmotic gradient ektacytometry (OGE) is currently considered the gold standard for the diagnosis of red cell membrane disorders, especially hereditary spherocytosis (HS). Impairment of red cell deformability, leading to a decrease in red cell survival rate, is the common trait of hereditary haemolytic anaemias; in general, it is the consequence of an abnormal cell shape, increased rigidity or dehydration. Up to now, the next-generation ektacytometry has been mainly used for the differential diagnosis of red blood cell membranopathies, but experience with structural hemoglobinopathies and thalassemia is still scarce. However, recently, many new forms of therapy are being developed for the treatment of hemoglobinopathies, particularly sickle-cell disease and β-thalassemia; clinical interest in ektacytometry is increasing and should be further explored. Here, we have evaluated the OGE profiles provided by the osmoscan module of the LoRRca ektacytometer in 96 patients with different hemoglobinopathies, both structural and thalassemia, with the aim of analysing their usefulness for the early diagnosis of these disorders either individually or in co-inheritance with other hereditary RBC defects. In addition, this study aims to improve our knowledge of the contribution of red cell deformability, osmotic fragility and intracellular viscosity to the physiopathology of haemolysis, especially when these disorders are a cause of rare anaemia. From this study, we conclude that the osmoscan profile provides complementary information on red cell deformability and hydration homeostasis that may contribute to the better understanding of the physiopathology of decreased red cell survival and hemolysis which is present in some patients. Full article

(This article belongs to the Special Issue Thalassaemia: A Complex Mix of Genetic Entities Challenging Healthcare Providers Globally)

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19 pages, 976 KiB

Open AccessReview

CRISPR Gene Therapy: A Promising One-Time Therapeutic Approach for Transfusion-Dependent β-Thalassemia—CRISPR-Cas9 Gene Editing for β-Thalassemia

Udani Gamage

Kesari Warnakulasuriya

Sonali Hansika

and

Gayathri N. Silva

Thalass. Rep. 2023, 13(1), 51-69; https://doi.org/10.3390/thalassrep13010006 - 06 Feb 2023

Cited by 1

Abstract

β-Thalassemia is an inherited hematological disorder that results from genetic changes in the β-globin gene, leading to the reduced or absent synthesis of β-globin. For several decades, the only curative treatment option for β-thalassemia has been allogeneic hematopoietic cell transplantation (allo-HCT). Nonetheless, rapid progress in genome modification technologies holds great potential for treating this disease and will soon change the current standard of care for β-thalassemia. For instance, the emergence of the CRISPR/Cas9 genome editing platform has opened the door for precision gene editing and can serve as an effective molecular treatment for a multitude of genetic diseases. Investigational studies were carried out to treat β-thalassemia patients utilizing CRISPR-based CTX001 therapy targeting the fetal hemoglobin silencer BCL11A to restore γ-globin expression in place of deficient β-globin. The results of recently carried out clinical trials provide hope of CTX001 being a promising one-time therapeutic option to treat β-hemoglobinopathies. This review provides an insight into the key scientific steps that led to the development and application of novel CRISPR/Cas9–based gene therapies as a promising therapeutic platform for transfusion-dependent β-thalassemia (TDT). Despite the resulting ethical, moral, and social challenges, CRISPR provides an excellent treatment option against hemoglobin-associated genetic diseases. Full article

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

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13 pages, 782 KiB

Open AccessFeature PaperReview

Cardiovascular Complications in β-Thalassemia: Getting to the Heart of It

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Thalass. Rep. 2023, 13(1), 38-50; https://doi.org/10.3390/thalassrep13010005 - 30 Jan 2023

Cited by 2

Abstract

Beta thalassemia is an inherited disorder resulting in abnormal or decreased production of hemoglobin, leading to hemolysis and chronic anemia. The long-term complications can affect multiple organ systems, namely the liver, heart, and endocrine. Myocardial iron overload is a common finding in β-thalassemia. As a result, different cardiovascular complications in the form of cardiomyopathy, pulmonary hypertension, arrhythmias, and vasculopathies can occur, and in extreme cases, sudden cardiac death. Each of these complications pertains to underlying etiologies and risk factors, which highlights the importance of early diagnosis and prevention. In this review, we will discuss different types of cardiovascular complications that can manifest in patients with β-thalassemia, in addition to the current diagnostic modalities, preventive and treatment modalities for these complications. Full article

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5 pages, 191 KiB

Open AccessPerspective

Juggling between the Cost and Value of New Therapies: Does Science Still Serve Patient Needs?

Androulla Eleftheriou

Saeed Jafaar Al-Awadhi

Sheikha Sheikha Bint Seif Al-Nahyan

Robert Ficarra

Michelle Abi Saad

Anton Skafi

Loris Angelo Brunetta

Fatemeh Hashemi

Eleni Michalaki

Abdul Baset Mohd Merdas

and

Michael Angastiniotis

Thalass. Rep. 2023, 13(1), 33-37; https://doi.org/10.3390/thalassrep13010004 - 28 Jan 2023

Abstract

Thalassaemia International Federation (TIF), representing the united voice of people with thalassaemia and their families globally, has been striving for more than three decades to empower research, by academic communities and industry, to focus on developing a safe and effective curative approach for thalassaemia. Such a cure would lead to new lives with equal opportunities and challenges, as for every other person not suffering from a severe chronic disease. A gene therapy product was finally authorised in May 2019 by the European Medicinal Agency, thus marking a milestone in the history of the disease. However, after this conditional authorization, everyone focused on numbers and opted for cost of illness and cost-effectiveness studies, inadmissibly ignoring patients’ voices and needs. The product was finally withdrawn from Europe, despite the fact that all implicated stakeholders, including governments, academia and industry always knew that an innovative and complex therapy would be expensive but always supported and fought for its development. In this article, TIF expresses its view on this issue, including some thoughts on how to address the high cost of innovative therapies. Full article

(This article belongs to the Special Issue Thalassaemia: A Complex Mix of Genetic Entities Challenging Healthcare Providers Globally)

12 pages, 1996 KiB

Open AccessTechnical Note

Beta-Thalassemia Minor and SARS-CoV-2: Physiopathology, Prevalence, Severity, Morbidity, and Mortality

Edouard Lansiaux

Emmanuel Drouin

and

Carsten Bolm

Thalass. Rep. 2023, 13(1), 21-32; https://doi.org/10.3390/thalassrep13010003 - 16 Jan 2023

Abstract

Background: Since the first year of the COVID-19 global pandemic, a hypothesis concerning the possible protection/immunity of beta-thalassemia carriers has remained in abeyance. Methods: Three databases (Pubmed Central, Scopus, and Google Scholar) were screened and checked in order to extract all studies about the incidence of confirmed COVID-19 cases, mortality rate, severity assessment, or ICU admission among patients with beta-thalassemia minor, were included in this analysis. The language was limited to English. Studies such as case reports, review studies, and studies that did not have complete data for calculating incidences were excluded. Results and discussion: a total of 3 studies out of 2265 were selected. According to our systematic-review meta-analysis, beta-thalassemia carriers could be less affected by COVID-19 than the general population [IRR = 0.9250 (0.5752; 1.4877)], affected by COVID-19 with a worst severity [OR = 1.5933 (0.4884; 5.1981)], less admissible into the ICU [IRR = 0.3620 (0.0025; 51.6821)], and more susceptible to die from COVID-19 or one of its consequences [IRR = 1.8542 (0.7819; 4.3970)]. However, all of those results remain insignificant with a bad p-value (respectively 0.7479, 0.4400, 0.6881, and 0.1610). Other large case-control or registry studies are needed to confirm these trends. Full article

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11 pages, 269 KiB

Open AccessFeature PaperArticle

TIF Standards for Haemoglobinopathy Reference Centres

Michael Angastiniotis

Androulla Eleftheriou

Mohammed Naveed

Ali Al Assaf

Andreas Polynikis

Elpidoforos S. Soteriades

and

Dimitrios Farmakis

Thalass. Rep. 2023, 13(1), 10-20; https://doi.org/10.3390/thalassrep13010002 - 23 Dec 2022

Abstract

Haemoglobin disorders are hereditary, lifelong and characterised by the need for multifaceted management. The question of quality in meeting standards of care that are likely to bring the best possible outcomes for patients is a necessary consideration. The concept of reference centres supporting peripheral treatment centres in a formal networking relationship is a response to the real needs of patients and a practical solution in public health terms. In this report, a team of advisors of Thalassaemia International Federation (TIF) attempts to suggest a set of standards for haemoglobinopathy reference centres, also based on the founding principles of TIF, aiming to act as a guideline for its member associations and professional collaborators. The standards described herein can form the basis of an accreditation process and also serve as a guide for those who would advocate for quality improvement for thalassaemia services. Full article

(This article belongs to the Special Issue Thalassaemia: A Complex Mix of Genetic Entities Challenging Healthcare Providers Globally)

9 pages, 818 KiB

Open AccessArticle

Impact of COVID-19 Pandemic on Pre-Transfusion Hemoglobin Level and Frequency of Transfusion in Transfusion-Dependent Thalassemia Patients in Indonesia

Ludi Dhyani Rahmartani

Micheylla Kusumaning Dewi

Stephen Diah Iskandar

Anastasia Michelle Pratanata

Ganda Ilmana

Teny Tjitra Sari

Anna Mira Lubis

and

Pustika Amalia Wahidiyat

Thalass. Rep. 2023, 13(1), 1-9; https://doi.org/10.3390/thalassrep13010001 - 22 Dec 2022

Abstract

Transfusion-dependent thalassemia is the most severe form of thalassemia; patients require regular blood transfusions to maintain their hemoglobin level. The COVID-19 pandemic has disrupted the routine measures for controlling chronic diseases like thalassemia. This study aims to measure the difference in pre-transfusion hemoglobin levels and the frequency of transfusions before and during pandemic. This retrospective cross-sectional study utilized medical record data of 101 transfusion-dependent thalassemia (TDT) patients treated in Cipto Mangunkusumo Hospital (CMH) from 2019–2021. The dependent variables of this study were pre-transfusion hemoglobin level and transfusion attendance. The pre-pandemic phase was defined as 30 March 2019 to 29 March 2020, whereas the during-pandemic phase was from 30 March 2020 to 29 March 2021. Up to 59.4% of subjects had suboptimal Hb levels of <9.0 g/dL, even before the pandemic, and this increased to 71.3% during the pandemic. The mean pre-transfusion hemoglobin level before the pandemic was 8.71 g/dL, and this decreased to 8.46 g/dL (p value < 0.001). Transfusion attendance before and during the pandemic showed no significant difference (p-value = 0.990). Our study shows poorer control of pre-transfusion Hb levels during the pandemic. This puts patients at higher risk of developing many long-term complications. Full article

(This article belongs to the Special Issue Thalassaemia: A Complex Mix of Genetic Entities Challenging Healthcare Providers Globally)

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