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Lancet (London, England) Dec 2023
Topics: Humans; Anemia, Sickle Cell; Pain Management; Genetic Therapy
PubMed: 38103934
DOI: 10.1016/S0140-6736(23)02797-6 -
Annals of Hematology May 2024Coronavirus disease 19 (COVID-19) is an infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) causing acute systemic disorders and multi-organ... (Review)
Review
Coronavirus disease 19 (COVID-19) is an infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) causing acute systemic disorders and multi-organ damage. β-thalassemia (β-T) is an autosomal recessive disorder leading to the development of anemia. β-T may lead to complications such as immunological disorders, iron overload, oxidative stress, and endocrinopathy. β-T and associated complications may increase the risk of SARS-CoV-2, as inflammatory disturbances and oxidative stress disorders are linked with COVID-19. Therefore, the objective of the present review was to elucidate the potential link between β-T and COVID-19 regarding the underlying comorbidities. The present review showed that most of the β-T patients with COVID-19 revealed mild to moderate clinical features, and β-T may not be linked with Covid-19 severity. Though patients with transfusion-dependent β-T (TDT) develop less COVID-19 severity compared to non-transfusion-depend β-T(NTDT), preclinical and clinical studies are recommended in this regard.
Topics: Humans; beta-Thalassemia; COVID-19; SARS-CoV-2; Blood Transfusion; Iron Overload
PubMed: 37405444
DOI: 10.1007/s00277-023-05346-8 -
Experimental Hematology Nov 2023Thalassemia is the most common monogenic disorder of red blood cells (RBCs) caused by defects in the synthesis of globin chains. Thalassemia phenotypes have a wide... (Review)
Review
Thalassemia is the most common monogenic disorder of red blood cells (RBCs) caused by defects in the synthesis of globin chains. Thalassemia phenotypes have a wide spectrum of clinical manifestations and vary from severe anemia requiring regular blood transfusions to clinically asymptomatic states. Ineffective erythropoiesis and toxicity caused by iron overload are major factors responsible for various complications in thalassemia patients, especially patients with β-thalassemia major (β-TM). Common complications in patients with thalassemia include iron overload, thrombosis, cardiac morbidity, vascular dysfunction, inflammation, and organ dysfunction. Extracellular vesicles (EVs) are small membrane vesicles released from various cells' plasma membranes due to activation and apoptosis. Based on studies, EVs play a role in various processes, including clot formation, vascular damage, and proinflammatory processes. In recent years, they have also been studied as biomarkers in the diagnosis and prognosis of diseases. Considering the high concentration of EVs in thalassemia and their role in cellular processes, this study reviews the role of EVs in the common complications of patients with β-thalassemia for the first time.
Topics: Humans; beta-Thalassemia; Iron Overload; Thalassemia; Hemoglobins; Extracellular Vesicles
PubMed: 37652128
DOI: 10.1016/j.exphem.2023.08.009 -
Journal of Pediatric Hematology/oncology Oct 2023Sickle cell disease (SCD) is a chronic hemolytic anemia that may be life-threatening due to multisystemic effects. Identification of the factors which affect the...
BACKGROUND AND AIMS
Sickle cell disease (SCD) is a chronic hemolytic anemia that may be life-threatening due to multisystemic effects. Identification of the factors which affect the pathophysiology of the disease is important in reducing mortality and morbidity. This study aimed to determine gut microbial diversity in children and adolescents with SCA compared with healthy volunteers and to evaluate the clinical impact of microbiota.
MATERIALS AND METHODS
The study included 34 children and young adolescents with SCD and 41 healthy volunteer participants. The microbiome was assessed by 16S rRNA sequencing in stool samples. Laboratory parameters of all participants, such as complete blood count and C-reactive protein values and clinical characteristics of SCD patients, were determined and compared, as well as clinical conditions of the patients, such as vascular occlusive crisis and/or acute chest syndrome, frequency of transfusions, intake of penicillin, hydroxyurea, and chelation therapy were recorded.
RESULTS
White blood cell count, hemoglobin, immature granulocyte and C-reactive protein levels were significantly higher in the patient group ( P <0.05). Microbiota analysis revealed 3 different clusters among subjects; controls and 2 clusters in the SCD patients (patient G1 and G2 groups). Bacteroides spp. were more prevalent, while Dialester spp. and Prevotella spp. were less prevalent in SCD compared with controls ( t =2.142, P <0.05). Patient G2 (n=9) had a higher prevalence of Bacteroides and a lower prevalence of Prevotella than patient G1 (n=25).
CONCLUSION
In our study, there was a difference between SCD patients and the control group, while 2 different microbiota profiles were encountered in SCD patients. This difference between the microbiota of the patients was not found to affect the clinical picture (such as vascular occlusive crisis, acute chest syndrome).
Topics: Adolescent; Humans; Child; Acute Chest Syndrome; Gastrointestinal Microbiome; C-Reactive Protein; RNA, Ribosomal, 16S; Anemia, Sickle Cell; Vascular Diseases
PubMed: 37526399
DOI: 10.1097/MPH.0000000000002725 -
International Journal of Molecular... Mar 2024Hemoglobinopathies are monogenic disorders affecting hemoglobin synthesis. Thalassemia and sickle cell disease (SCD) are considered the two major hemoglobinopathies.... (Review)
Review
Hemoglobinopathies are monogenic disorders affecting hemoglobin synthesis. Thalassemia and sickle cell disease (SCD) are considered the two major hemoglobinopathies. Thalassemia is a genetic disorder and one of the major hemoglobinopathies determined by an impairment of globin chain production, which causes an alteration of erythropoiesis, an improvement in hemolysis, and an alteration of iron homoeostasis. In SCD, the mutations are on the β-globin chain of hemoglobin which results in a substitution of glutamic acid by valine with consequent formation of Hemoglobin S (HbS). Several factors are involved in bone metabolism alteration in patients with hemoglobinopathies, among them hormonal deficiency, bone marrow hyperplasia, iron overload, inflammation, and increased bone turnover. Bone metabolism is the result of balance maintenance between bone deposition and bone resorption, by osteoblasts (OBs) and osteoclasts (OCs). An impairment of this balance is responsible for the onset of bone diseases, such as osteoporosis (OP). Therefore, here we will discuss the alteration of bone metabolism in patients with hemoglobinopathies and the possible therapeutic strategies to contain and/or counteract bone health impairment in these patients, taking into consideration not only the pharmacological treatments already used in the clinical armamentarium, but also the new possible therapeutic strategies.
Topics: Humans; Bone Density; Hemoglobinopathies; Anemia, Sickle Cell; Thalassemia; Hemoglobin, Sickle; beta-Thalassemia
PubMed: 38474150
DOI: 10.3390/ijms25052902 -
British Journal of Haematology Dec 2023Although descriptions of quality of life and patient reports of mood in sickle cell disease (SCD) have become more common in the literature, less is known about... (Review)
Review
Although descriptions of quality of life and patient reports of mood in sickle cell disease (SCD) have become more common in the literature, less is known about psychiatric illness prevalence, presentation, and treatment, particularly for adults. We provide a narrative review of what is known about common and debilitating psychiatric conditions such as depression, anxiety, and cognitive impairment, specifically for adults with SCD. We discuss the limitations of the current evidence, make provisional recommendations, and identify opportunities for research and improved care.
Topics: Adult; Humans; Anemia, Sickle Cell; Anxiety; Cognitive Dysfunction; Comorbidity; Quality of Life; Depression
PubMed: 37455514
DOI: 10.1111/bjh.18981 -
Blood Apr 2024
Topics: Child; Humans; Hydroxyurea; Uganda; Anemia, Sickle Cell
PubMed: 38573609
DOI: 10.1182/blood.2023023688 -
Postgraduate Medicine Nov 2023Hemoglobinopathies are a global public health problem with high mortality and morbidity and very expensive treatment. Disease can be reduced and prevented with...
OBJECTIVES
Hemoglobinopathies are a global public health problem with high mortality and morbidity and very expensive treatment. Disease can be reduced and prevented with hemoglobinopathy screening tests. It is possible to identify carriers with the hemoglobinopathy screening program applied in many countries of the world and in Turkey. This study aims to evaluate the results of the national premarital hemoglobinopathy screening program carried out in primary healthcare institutions.
METHODS
The research is of epidemiological and cross-sectional type. Electrophoresis results examined within the scope of the premarital hemoglobinopathy screening program in Samsun between 1 January 2019 and 31 December 2021 were evaluated retrospectively. Age, gender, year of screening, and hemoglobinopathy screening results were obtained from the records. In the statistical analysis of the data, < 0.05 was accepted.
RESULTS
The median age of 52,338 people screened under the hemoglobinopathy screening program was 29.0 (16.0-86.0) years. About 54.1% ( = 28,309) of those who were screened were female, and it was found that the least screening was done in 2020 ( = 15,765 (30.1%)). As a result of the screening, the frequency of the β-thalassemia (β-thal) trait was 1.37% ( = 676), the frequency of the abnormal HbS was 0.04% ( = 20). The frequency of β-thal trait was statistically significantly higher in 2020 (1.5%) compared to other years ( = 0.029). When the results were analyzed by gender, the rate of women with abnormal HbS (3.7%) was significantly higher than the others ( = 0.017).
CONCLUSIONS
This study presents the results of the national hemoglobinopathy screening program in Northern Turkey and the β-thal and the abnormal HbS rates were found to be low. The data obtained will be useful in monitoring hemoglobinopathy disorders and evaluating the current program's effectiveness in the future. It will allow decision-makers to implement policy changes and prioritize new programs.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; beta-Thalassemia; Black Sea; Cross-Sectional Studies; Hemoglobinopathies; Premarital Examinations; Prevalence; Retrospective Studies; Turkey; Adolescent; Young Adult
PubMed: 38019185
DOI: 10.1080/00325481.2023.2285726 -
Cytotherapy Dec 2023Amidst the success of cell therapy for the treatment of onco-hematological diseases, the first recently Food and Drug Administration-approved gene therapy product for...
BACKGROUND AIMS
Amidst the success of cell therapy for the treatment of onco-hematological diseases, the first recently Food and Drug Administration-approved gene therapy product for patients with transfusion-dependent β-thalassemia (TDT) indicates the feasibility of gene therapy as curative for genetic hematologic disorders. This work analyzed the current-world scenario of clinical trials involving gene therapy for β-hemoglobinopathies.
METHODS
Eighteen trials for patients with sickle cell disease (SCD) and 24 for patients with TDT were analyzed.
RESULTS
Most are phase 1 and 2 trials, funded by the industry and are currently recruiting volunteers. Treatment strategies for both diseases are fetal hemoglobin induction (52.4%); addition of wild-type or therapeutic β-globin gene (38.1%) and correction of mutations (9,5%). Gene editing (52.4%) and gene addition (40.5%) are the two most used techniques. The United States and France are the countries with the greatest number of clinical trials centers for SCD, with 83.1% and 4.2%, respectively. The United States (41.1%), China (26%) and Italy (6.8%) lead TDT trials centers.
CONCLUSIONS
Geographic trial concentration indicates the high costs of this technology, logistical issues and social challenges that need to be overcome for gene therapy to reach low- and middle-income countries where SCD and TDT are prevalent and where they most impact the patient's health.
Topics: Humans; Hemoglobinopathies; Anemia, Sickle Cell; Cell- and Tissue-Based Therapy; China; Genetic Therapy
PubMed: 37318395
DOI: 10.1016/j.jcyt.2023.05.006 -
International Journal of Molecular... Apr 2024In this short review we have presented and discussed studies on pharmacogenomics (also termed pharmacogenetics) of the drugs employed in the treatment of β-thalassemia... (Review)
Review
In this short review we have presented and discussed studies on pharmacogenomics (also termed pharmacogenetics) of the drugs employed in the treatment of β-thalassemia or Sickle-cell disease (SCD). This field of investigation is relevant, since it is expected to help clinicians select the appropriate drug and the correct dosage for each patient. We first discussed the search for DNA polymorphisms associated with a high expression of γ-globin genes and identified this using GWAS studies and CRISPR-based gene editing approaches. We then presented validated DNA polymorphisms associated with a high HbF production (including, but not limited to the XmnI polymorphism and those related to the , , , and genes). The expression of microRNAs involved in the regulation of γ-globin genes was also presented in the context of pharmacomiRNomics. Then, the pharmacogenomics of validated fetal hemoglobin inducers (hydroxyurea, butyrate and butyrate analogues, thalidomide, and sirolimus), of iron chelators, and of analgesics in the pain management of SCD patients were considered. Finally, we discuss current clinical trials, as well as international research networks focusing on clinical issues related to pharmacogenomics in hematological diseases.
Topics: Humans; Anemia, Sickle Cell; beta-Thalassemia; Pharmacogenetics; Fetal Hemoglobin; gamma-Globins; Iron Chelating Agents
PubMed: 38673849
DOI: 10.3390/ijms25084263