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Hemoglobin Sep 2023Thalassemia is a major public health concern in India. The thalassemic burden in India is high, with an estimated 100,000 patients diagnosed with β-thalassemia... (Review)
Review
Thalassemia is a major public health concern in India. The thalassemic burden in India is high, with an estimated 100,000 patients diagnosed with β-thalassemia syndrome. However, the exact number is unknown because of the absence of National Registries for patients. India alone contributes to approximately 25% of the global β-thalassemia burden. A possible option to control this burden is to endorse education and awareness programs, compulsory prenatal screening, and develop suitable facilities for genetic counseling, and availability of cost-effective diagnostic tests in India, especially in rural areas. In addition to the various clinical complications associated with thalassemia, lifelong intervention creates mental and physical trauma in patients and their relatives. Government and nongovernment organizations have initiated screening programs to prevent thalassemia. However, prenatal screening is not mandatory, and the reachability of screening programs in rural areas is yet to begin. This review article will discuss the progress in thalassemia research in India, including its prevalence, spectrum of β-thalassemia mutations, preventive and therapeutic measures, and awareness programs. More importantly, we will discuss the need and roadmap to strengthen prevention programs in India.
Topics: Pregnancy; Female; Humans; beta-Thalassemia; Prenatal Diagnosis; Thalassemia; Genetic Counseling; India
PubMed: 37947120
DOI: 10.1080/03630269.2023.2269837 -
Presse Medicale (Paris, France : 1983) Dec 2023Sickle Cell Disease (SCD) is a hereditary blood disorder characterized by the presence of abnormal hemoglobin, leading to the formation of sickle-shaped red blood cells,... (Review)
Review
Sickle Cell Disease (SCD) is a hereditary blood disorder characterized by the presence of abnormal hemoglobin, leading to the formation of sickle-shaped red blood cells, causing vaso-occlusion. Inflammation is a key component of the pathophysiology of SCD, contributing to the vascular complications and tissue damage. This review is centered on exploring the role of the inflammatory complement system in the pathophysiology of SCD. Our goal is to offer a comprehensive summary of the existing evidence regarding complement activation in patients with SCD, encompassing both steady-state conditions and episodes of vaso-occlusive events. Additionally, we will discuss the proposed mechanisms by which the complement system may contribute to tissue injury in this pathology. Finally, we will provide an overview of the available evidence concerning the effectiveness of therapeutic interventions aimed at blocking the complement system in the context of SCD and discuss the perspective of complement inhibition.
Topics: Humans; Anemia, Sickle Cell; Vascular Diseases; Inflammation
PubMed: 37972851
DOI: 10.1016/j.lpm.2023.104205 -
Blood Mar 2024
Topics: Adult; Humans; beta-Thalassemia; Thalassemia; Hematologic Diseases; Hemoglobins
PubMed: 38451517
DOI: 10.1182/blood.2023023294 -
Clinical Chemistry Jul 2023Large β-globin gene cluster deletions (hereditary persistence of fetal hemoglobin [Hb] or β-, δβ-, γδβ-, and ϵγδβ-thalassemia), are associated with widely...
BACKGROUND
Large β-globin gene cluster deletions (hereditary persistence of fetal hemoglobin [Hb] or β-, δβ-, γδβ-, and ϵγδβ-thalassemia), are associated with widely disparate phenotypes, including variable degrees of microcytic anemia and Hb F levels. When present, increased Hb A2 is used as a surrogate marker for β-thalassemia. Notably, ϵγδβ-thalassemias lack the essential regulatory locus control region (LCR) and cause severe transient perinatal anemia but normal newborn screen (NBS) results and Hb A2 levels. Herein, we report a novel deletion of the ϵ, Aγ, Gγ, and ψβ loci with intact LCR, δ-, and β-regions in 2 women and newborn twins.
METHODS
Capillary electrophoresis (CE), high-performance liquid chromatography (HPLC), DNA sequencing, multiplex ligation-dependent probe amplification (MLPA), gap-polymerase chain reaction (gap-PCR), and long-read sequencing (LRS) were performed.
RESULTS
NBS showed an Hb A > Hb F pattern for both twins. At 20 months, Hb A2 was increased similarly to that in the mother and an unrelated woman. Unexplained microcytosis was absent and the twins lacked severe neonatal anemia. MLPA, LRS, and gap-PCR confirmed a 32 599 base pair deletion of ϵ (HBE1) through ψβ (HBBP1) loci.
CONCLUSIONS
This deletion represents a hemoglobinopathy category with a distinct phenotype that has not been previously described, an ϵγ-thalassemia. Both the NBS Hb A > F pattern and the subsequent increased Hb A2 without microcytosis are unusual. A similar deletion should be considered when this pattern is encountered and appropriate test methods selected for detection. Knowledge of the clinical impact of this new category will improve genetic counselling, with distinction from the severe transient anemia associated with ϵγδβ-thalassemia.
Topics: Humans; Female; Thalassemia; Hemoglobinopathies; beta-Thalassemia; Fetal Hemoglobin; Multiplex Polymerase Chain Reaction
PubMed: 37086467
DOI: 10.1093/clinchem/hvad038 -
JAMA Network Open Nov 2023Despite hydroxyurea being an established treatment for sickle cell disease (SCD), it remains underused. The recent approval of the disease-modifying treatments (DMTs)...
IMPORTANCE
Despite hydroxyurea being an established treatment for sickle cell disease (SCD), it remains underused. The recent approval of the disease-modifying treatments (DMTs) l-glutamine, crizanlizumab, and voxelotor underscores the need to understand the uptake of DMTs in the current treatment landscape.
OBJECTIVE
To explore characteristics that may be associated with DMT use and to describe observed patterns of yearly DMT use from 2014 to 2021.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study used administrative claims data from Optum's deidentified Clinformatics Data Mart Database from January 1, 2014, to September 30, 2021, to identify adults and children with SCD. Data were analyzed from August 1, 2022, to August 28, 2023.
EXPOSURE
Use of DMTs.
MAIN OUTCOMES AND MEASURES
Patient characteristics across groups with varying patterns of DMT use and yearly patterns of prescription fills for hydroxyurea, crizanlizumab, voxelotor, and l-glutamine.
RESULTS
A total of 5022 beneficiaries with SCD (2081 [41.4%] aged 18-45 years; 2929 [58.3%] female) were included in sample A (144 [2.9%] inconsistent users, 274 [5.5%] incident users, 892 [17.8%] consistent users, and 3712 [73.9%] non-DMT users). Inconsistent users had a higher prevalence of vaso-occlusive crises (mean [SD], 3.7 [4.7]), splenic complications (6 of 144 [4.2%]), pulmonary complications (36 of 144 [25.0%]), kidney disease (21 of 144 [14.6%]), acute chest syndrome (18 of 144 [12.5%]), and health care visits (eg, mean [SD] inpatient visits, 7.0 [10.7]) compared with the other use groups. Non-DMT users had the lowest prevalence of vaso-occlusive crises (mean [SD], 0.8 [2.4]), acute chest syndrome (109 of 3712 [2.9%]), and inpatient (mean [SD], 2.0 [6.6]) and emergency department (mean [SD], 0.7 [3.1]) visits and the highest proportion of adults 65 years and older (593 of 3712 [16.0%]). In sample B (6387 beneficiaries with SCD), hydroxyurea use modestly increased from 428 of 2188 participants (19.6%) in 2014 to 701 of 2880 (24.3%) in 2021. Use of l-glutamine increased briefly but gradually decreased throughout the study period. In 2021, out of 2880 participants, 102 (3.5%) had at least 1 fill for crizanlizumab and 131 (4.6%) had at least 1 fill for voxelotor. Overall, total DMT use increased from 428 of 2188 participants (19.6%) in 2014 to 815 of 2880 patients (28.3%) in 2021.
CONCLUSIONS AND RELEVANCE
In this cross-sectional analysis of adults and children with SCD, uptake of DMTs remained low from 2014 to 2021, despite the approval of newer therapies. Notable differences in patient characteristics across varied DMT exposure types necessitate further exploration into factors that facilitate DMT use and the creation of strategies to enhance DMT uptake.
Topics: Adult; Child; Humans; Female; Male; Acute Chest Syndrome; Cross-Sectional Studies; Glutamine; Hydroxyurea; Anemia, Sickle Cell; Inpatients
PubMed: 37991760
DOI: 10.1001/jamanetworkopen.2023.44546 -
The Lancet. Haematology Aug 2023Sickle cell disease is a hereditary multiorgan disease that is considered rare in the EU. In 2017, the Rare Diseases Plan was implemented within the EU and 24 European... (Review)
Review
Sickle cell disease is a hereditary multiorgan disease that is considered rare in the EU. In 2017, the Rare Diseases Plan was implemented within the EU and 24 European Reference Networks (ERNs) were created, including the ERN on Rare Haematological Diseases (ERN-EuroBloodNet), dedicated to rare haematological diseases. This EU initiative has made it possible to accentuate existing collaborations and create new ones. The project also made it possible to list all the needs of people with rare haematological diseases not yet covered health-care providers in the EU to allow optimised care of individuals with rare pathologies, including sickle cell disease. This Viewpoint is the result of joint work within 12 EU member states (ie, Belgium, Cyprus, Denmark, France, Germany, Greece, Ireland, Italy, Portugal, Spain, Sweden, and The Netherlands), all members of the ERN-EuroBloodNet. We describe the role of the ERN-EuroBloodNet to improve the overall approach to and the management of individuals with sickle cell disease in the EU through specific on the pooling of expertise, knowledge, and best practices; the development of training and education programmes; the strategy for systematic gathering and standardisation of clinical data; and its reuse in clinical research. Epidemiology and research strategies from ongoing implementation of the Rare Anaemia Disorders European Epidemiological Platform is depicted.
Topics: Humans; Netherlands; Germany; Greece; Italy; Rare Diseases; Anemia, Sickle Cell; Europe
PubMed: 37451300
DOI: 10.1016/S2352-3026(23)00182-5 -
Clinical Chemistry Jul 2023
Topics: Humans; beta-Globins; Thalassemia; Mutation; Hemoglobinopathies
PubMed: 37279577
DOI: 10.1093/clinchem/hvad067 -
Transfusion and Apheresis Science :... Oct 2023Sickle cell disease (SCD) is the most common hereditary hemoglobinopathy. The underlying pathophysiology of the red blood cell (RBC) leads to pan-systemic complications... (Review)
Review
Sickle cell disease (SCD) is the most common hereditary hemoglobinopathy. The underlying pathophysiology of the red blood cell (RBC) leads to pan-systemic complications which manifest at an early age. While curative and disease-modifying treatments exist for SCD, a key intervention in the management and treatment of SCD is RBC transfusion, which can alleviate or prevent many complications. SCD patients often require chronic RBC transfusion therapy which can result in complications, such as iron overload, alloimmunization and infection. In low- and middle-income countries (LMICs), SCD patients lack appropriate access to healthcare such as newborn screening, health education, prophylaxis for infection, and treatments to reduce both mortality and SCD-related adverse effects. Poor access to RBCs for transfusion, coupled with donated blood not meeting safety standards set by the World Health Organization, presents a significant barrier for patients requiring chronic transfusions in LMICs. Unmet needs associated with blood collection, blood component processing and recipient matching all pose a serious problem in many LMICs, although this varies depending on geographic location, political organizations and economy. This review aims to provide an overview of the global burden of SCD, focusing on the availability of current treatments and the burden of chronic RBC transfusions in patients with SCD.
Topics: Infant, Newborn; Humans; Anemia, Sickle Cell; Blood Transfusion; Erythrocytes; Erythrocyte Transfusion; Blood Group Incompatibility
PubMed: 37541800
DOI: 10.1016/j.transci.2023.103764 -
Gene Feb 2024One excellent illustration of how a single gene abnormality may result in a spectrum of disease incidence is the incredible phenotypic variety of β-thalassemia, which... (Review)
Review
One excellent illustration of how a single gene abnormality may result in a spectrum of disease incidence is the incredible phenotypic variety of β-thalassemia, which spans from severe anemia and transfusion needs to an utterly asymptomatic sickness. However, genetic causes of β-thalassemia and how the anemia's severity might be altered at various stages in its pathophysiology have been well investigated. There are currently known to be more than 350 mutations that cause genetic disease. However only 20 β thalassemia mutations account for more than 80% of the β thalassemia mutation across the globe due to phenomenon of geographical clustering where each population has a few common mutations together with a varying number of rare ones. Due to migration of the population, the spectrum of thalassemia mutation in changing from time to time. In this review, efforts are made to collate β globin gene mutations in different countries and populations.
Topics: Humans; beta-Thalassemia; Mutation; Thalassemia; beta-Globins; Geography
PubMed: 38007159
DOI: 10.1016/j.gene.2023.148022 -
Endocrinology and Metabolism Clinics of... Dec 2023Racial and ethnic disparities exist in the prevalence and management of osteoporosis, metastatic cancer, and sickle cell disease. Despite being the most common metabolic... (Review)
Review
Racial and ethnic disparities exist in the prevalence and management of osteoporosis, metastatic cancer, and sickle cell disease. Despite being the most common metabolic bone disease, osteoporosis remains underscreened and undertreated among Black women. Skeletal-related events in metastatic cancer include bone pain, pathologic fractures, and spinal cord compression. Disparities in screening for and treating skeletal-related events disproportionately affect Black patients. Metabolic bone disease contributes significantly to morbidity in sickle cell disease; however, clinical guidelines for screening and treatment do not currently exist. Clinical care recommendations are provided to raise awareness, close health care gaps, and guide future research efforts.
Topics: Humans; Female; Osteoporosis; Delivery of Health Care; Neoplasms; Anemia, Sickle Cell
PubMed: 37865478
DOI: 10.1016/j.ecl.2023.05.004