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CMAJ : Canadian Medical Association... Oct 2020
Topics: Diabetes Mellitus; Erythrocyte Indices; Humans; Iron Overload; Referral and Consultation; Thalassemia
PubMed: 33051316
DOI: 10.1503/cmaj.191613 -
Hemoglobin Jan 2022Indonesia is located along the 'Thalassemia Belt' and a hotspot for hemoglobinopathies. Around 3.0-10.0% of the population carry β-thalassemia (β-thal) and 2.6-11.0%... (Review)
Review
Indonesia is located along the 'Thalassemia Belt' and a hotspot for hemoglobinopathies. Around 3.0-10.0% of the population carry β-thalassemia (β-thal) and 2.6-11.0% of the population carry α-thalassemia (α-thal). It is estimated that around 2500 babies are born with β-thal major (β-TM) each year. At present, the cornerstone of treatment for β-TM in Indonesia remains supportive, including blood transfusions and iron chelation therapy. Hemovigilance systems in some cities are poor and it increases the risk of transfusion-transmitted infections and transfusion reactions. The availability of iron chelators remains uncertain, even in some rural areas, iron chelators do not exist. The poor adherence to iron chelation therapy and maintaining pretransfusion hemoglobin (Hb) levels above 9.0 g/dL are still a major issue in Indonesia. The cost of blood transfusion and iron chelation are covered by national health insurance. In line with the rise of life expectancy, the financial burden of thalassemia in Indonesia is increasing sharply. Thus, optimizing preventive programs may be the most suitable option for the current thalassemia condition in Indonesia.
Topics: Humans; Indonesia; Iron; Iron Chelating Agents; Transfusion Reaction; alpha-Thalassemia; beta-Thalassemia
PubMed: 35950580
DOI: 10.1080/03630269.2021.2023565 -
Cleveland Clinic Journal of Medicine Jan 2020Sickle cell disease (SCD) is the most common hemoglobinopathy in the United States and causes significant disease-related morbidity including multiorgan damage, chronic... (Review)
Review
Sickle cell disease (SCD) is the most common hemoglobinopathy in the United States and causes significant disease-related morbidity including multiorgan damage, chronic anemia, and debilitating pain crises. Primary care physicians play a key role in the medical home model of care for adults with SCD. This review focuses on current recommendations for health maintenance and provides a brief summary of disease complications and current updates.
Topics: Adolescent; Adult; Anemia, Sickle Cell; Female; Humans; Male; Patient-Centered Care; Primary Health Care; United States; Young Adult
PubMed: 31990651
DOI: 10.3949/ccjm.87a.18051 -
Hematology/oncology Clinics of North... Aug 2022β-thalassemia and sickle cell disease (SCD) are the most common monogenic diseases in the world and are potentially curable after allogeneic hematopoietic stem cell... (Review)
Review
β-thalassemia and sickle cell disease (SCD) are the most common monogenic diseases in the world and are potentially curable after allogeneic hematopoietic stem cell transplantation (HSCT) or autologous HSCT after genetic modification. Autologous gene therapy has the potential to offer a universal cure that overcomes many limitations of allogeneic HSCT including the lack of available donors, graft-vs-host disease, and graft rejection. Significant progress in gene therapy for the hemoglobinopathies has been made over the last several decades, now with multiple ongoing clinical trials investigating both gene addition and gene-editing strategies. Available results from a small number of patients, some with relatively short follow-up, are promising, with current efforts focused on continuing to improve the efficacy, durability, and safety of gene therapies for the cure of hemoglobin disorders.
Topics: Anemia, Sickle Cell; Genetic Therapy; Hematopoietic Stem Cell Transplantation; Hemoglobinopathies; Humans; beta-Thalassemia
PubMed: 35773052
DOI: 10.1016/j.hoc.2022.03.008 -
Internal and Emergency Medicine Oct 2019Sickle cell disease (SCD) is the most important hemoglobinopathy worldwide in terms of frequency and social impact, recently recognized as a global public health problem... (Review)
Review
Sickle cell disease (SCD) is the most important hemoglobinopathy worldwide in terms of frequency and social impact, recently recognized as a global public health problem by the World Health Organization. It is a monogenic but multisystem disorder with high morbidity and mortality. Vaso-occlusion, hemolytic anemia and vasculopathy are the hallmarks of SCD pathophysiology. This review focuses both on "time-dependent" acute clinical manifestations of SCD and chronic complications commonly described in adults with SCD. The review covers a broad spectrum of topics concerning current management of SCD targeted at the internists and emergency specialists who are increasingly involved in the care of acute and chronic complications of SCD patients.
Topics: Anemia, Sickle Cell; Disease Management; Humans; Internal Medicine
PubMed: 31385153
DOI: 10.1007/s11739-019-02160-x -
Hemoglobin Jan 2022India bears a huge burden of hemoglobinopathies, and the most prevalent is thalassemia. The different types of thalassemia include minor, major and intermedia, based on... (Review)
Review
India bears a huge burden of hemoglobinopathies, and the most prevalent is thalassemia. The different types of thalassemia include minor, major and intermedia, based on the α/β-globin chain inequality. This review aimed to understand the current prevalence of thalassemia in different regions of India and communities affected by it, along with the management of β-thalassemia major (β-TM) and β-thalassemia (β-thal) minor patients. A comprehensive electronic search for relevant articles was conducted using two databases, PubMed and Science Direct. Articles published in English from India between January 2009 and September 2021 were included. Studies from other countries, genetic and molecular characterization studies, and articles published in other languages were excluded. The prevalence of β-thal trait in Central India ranged between 1.4 and 3.4%, while 0.94% β-TM was reported among the patients with anemia. In South India, the prevalence of β-thal trait was between 8.50 and 37.90% and β-TM was reported to be between 2.30 and 7.47%. Northern and Western Indian states had a higher thalassemic burden. In Eastern India, tribal populations had a higher prevalence of β-thal trait (0.00-30.50%), β-TM (0.36-13.20%) and other hemoglobinopathies [Hb E (: c.79G>A)/β-thal] (0.04-15.45%) than nontribal populations. Additionally, scheduled castes, scheduled tribes and other backward classes of low socioeconomic status and low literacy rates were affected by β-thal. Almost all Indian states reported β-thal; however, it is mostly concentrated in eastern and western parts of the country. Well-integrated strategies and effective implementation are needed at State and National levels to minimize the burden of β-thal.
Topics: Hemoglobinopathies; Humans; India; Mutation; Prevalence; alpha-Thalassemia; beta-Globins; beta-Thalassemia
PubMed: 35129043
DOI: 10.1080/03630269.2021.2001346 -
British Journal of Haematology Apr 2023The thalassaemias are a group of genetic disorders of haemoglobin which are endemic in the tropics but are now found worldwide due to migration. Basic standard of care... (Review)
Review
The thalassaemias are a group of genetic disorders of haemoglobin which are endemic in the tropics but are now found worldwide due to migration. Basic standard of care therapy includes regular transfusions to maintain a haemoglobin level of around 10 g/dL, together with iron chelation therapy to prevent iron overload. Novel therapies, bone marrow transplantation, and gene therapy are treatment options that are unavailable in many countries with stressed economies. This Wider Perspectives article presents the strategies for management of an adolescent refugee patient with beta thalassaemia, as it would be performed by expert haematologists in six countries: Italy, Lebanon, Oman, the Sudan, Thailand and the United States. The experienced clinicians in each country have adapted their practice according to the resources available, which vary greatly. Even in the current modern era, providing adequate transfusions and chelation is problematic in many countries. On the other hand, ensuring adherence to therapy, particularly during adolescence, is a similar challenge seen in all countries. The concluding section highlights the disparities in available therapies and puts the role of novel therapies into a societal context.
Topics: Adolescent; Humans; Thalassemia; beta-Thalassemia; Chelation Therapy; Iron Overload; Blood Transfusion
PubMed: 36799486
DOI: 10.1111/bjh.18671 -
Proteomics May 2020An enormous amount of research effort has been devoted to biomarker discovery and validation. With the completion of the human genome, proteomics is now playing an... (Review)
Review
An enormous amount of research effort has been devoted to biomarker discovery and validation. With the completion of the human genome, proteomics is now playing an increasing role in this search for new and better biomarkers. Here, what leads to successful biomarker development is reviewed and how these features may be applied in the context of proteomic biomarker research is considered. The "fit-for-purpose" approach to biomarker development suggests that untargeted proteomic approaches may be better suited for early stages of biomarker discovery, while targeted approaches are preferred for validation and implementation. A systematic screening of published biomarker articles using MS-based proteomics reveals that while both targeted and untargeted technologies are used in proteomic biomarker development, most researchers do not combine these approaches. i) The reasons for this discrepancy, (ii) how proteomic technologies can overcome technical challenges that seem to limit their translation into the clinic, and (iii) how MS can improve, complement, or replace existing clinically important assays in the future are discussed.
Topics: Biomarkers; Biomedical Research; Hemoglobinopathies; Humans; Immunoassay; Mass Spectrometry; Prostate-Specific Antigen; Protein Isoforms; Proteins; Proteomics; Reproducibility of Results
PubMed: 31729135
DOI: 10.1002/pmic.201900029 -
Indian Journal of Pediatrics Jan 2020Hemolytic anemias are a group of disorders with varied clinical and molecular heterogeneity. They are characterized by decreased levels of circulating erythrocytes in... (Review)
Review
Hemolytic anemias are a group of disorders with varied clinical and molecular heterogeneity. They are characterized by decreased levels of circulating erythrocytes in blood. The pathognomic finding is a reduced red cell life span with severe anemia or, compensated hemolysis accompanied by reticulocytosis. The diagnostic workup or laboratory approach for hemolytic anemias is based on methodical step-wise testing which includes red blood cell morphology, hematological indices with increased reticulocyte count along with clinical features of hemolytic anemias. If conventional laboratory tests are unable to detect the underlying cause of hemolysis, genetic testing is recommended. Sanger sequencing along with conventional testing is the most efficient way to diagnose the underlying genetic causes, especially in thalassemias/hemoglobinopathies, if required. However, hemolytic anemias being highly heterogeneous disorders, next-generation sequencing-based screening is rapidly becoming an efficient way to decipher the etiologies where common causes have been excluded.
Topics: Anemia, Hemolytic; Anemia, Hemolytic, Congenital Nonspherocytic; Clinical Laboratory Techniques; Elliptocytosis, Hereditary; Erythrocytes; Genetic Testing; Glucosephosphate Dehydrogenase Deficiency; Hematologic Tests; Hemoglobinopathies; Hemoglobinuria, Paroxysmal; Hemolysis; High-Throughput Nucleotide Sequencing; Humans; Pyruvate Kinase; Pyruvate Metabolism, Inborn Errors; Reticulocyte Count; Spherocytosis, Hereditary; Thalassemia
PubMed: 31823208
DOI: 10.1007/s12098-019-03119-8 -
Progress in Molecular Biology and... 2021β-hemoglobinopathies are the most common monogenic disorders worldwide and are caused by mutations in the β-globin locus altering the production of adult hemoglobin...
β-hemoglobinopathies are the most common monogenic disorders worldwide and are caused by mutations in the β-globin locus altering the production of adult hemoglobin (HbA). Transplantation of autologous hematopoietic stem cells (HSCs) corrected by lentiviral vector-mediated addition of a functional β-like globin raised new hopes to treat sickle cell disease and β-thalassemia patients; however, the low expression of the therapeutic gene per vector copy is often not sufficient to fully correct the patients with a severe clinical phenotype. Recent advances in the genome editing field brought new possibilities to cure β-hemoglobinopathies by allowing the direct modification of specific endogenous loci. Double-strand breaks (DSBs)-inducing nucleases (i.e., ZFNs, TALENs and CRISPR-Cas9) or DSB-free tools (i.e., base and prime editing) have been used to directly correct the disease-causing mutations, restoring HbA expression, or to reactivate the expression of the fetal hemoglobin (HbF), which is known to alleviate clinical symptoms of β-hemoglobinopathy patients. Here, we describe the different genome editing tools, their application to develop therapeutic approaches to β-hemoglobinopathies and ongoing clinical trials using genome editing strategies.
Topics: Fetal Hemoglobin; Gene Editing; Hemoglobinopathies; Humans; beta-Globins; beta-Thalassemia
PubMed: 34175041
DOI: 10.1016/bs.pmbts.2021.01.025