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Australian Journal of General Practice Mar 2019Anaemia in pregnancy is a common medical condition managed by general practitioners (GPs) in Australia.
BACKGROUND
Anaemia in pregnancy is a common medical condition managed by general practitioners (GPs) in Australia.
OBJECTIVE
The aim of this article is to raise awareness of anaemia that occurs in pregnancy, understand its increasing complexities with an expanding migrant population, identify at-risk groups and promote appropriate management.
DISCUSSION
With anaemia reportedly occurring in 25% of women in pregnancy and GPs managing the majority of preconception and early pregnancy care, it is important to have a sound understanding of the aetiology, risks and management options. While iron deficiency anaemia is most commonly seen, a more complex understanding in regard to other causes and haemoglobinopathy screening is required.
Topics: Adult; Anemia; Anemia, Iron-Deficiency; Australia; Avitaminosis; Female; Helminthiasis; Hemoglobinopathies; Humans; Iron; Iron Deficiencies; Mass Screening; Pregnancy; Pregnancy Complications; Prenatal Care
PubMed: 31256475
DOI: 10.31128/AJGP-08-18-4664 -
Viruses Mar 2023Investigations to understand the function and control of the globin genes have led to some of the most exciting molecular discoveries and biomedical breakthroughs of the... (Review)
Review
Investigations to understand the function and control of the globin genes have led to some of the most exciting molecular discoveries and biomedical breakthroughs of the 20th and 21st centuries. Extensive characterization of the globin gene locus, accompanied by pioneering work on the utilization of viruses as human gene delivery tools in human hematopoietic stem and progenitor cells (HPSCs), has led to transformative and successful therapies via autologous hematopoietic stem-cell transplant with gene therapy (HSCT-GT). Due to the advanced understanding of the β-globin gene cluster, the first diseases considered for autologous HSCT-GT were two prevalent β-hemoglobinopathies: sickle cell disease and β-thalassemia, both affecting functional β-globin chains and leading to substantial morbidity. Both conditions are suitable for allogeneic HSCT; however, this therapy comes with serious risks and is most effective using an HLA-matched family donor (which is not available for most patients) to obtain optimal therapeutic and safe benefits. Transplants from unrelated or haplo-identical donors carry higher risks, although they are progressively improving. Conversely, HSCT-GT utilizes the patient's own HSPCs, broadening access to more patients. Several gene therapy clinical trials have been reported to have achieved significant disease improvement, and more are underway. Based on the safety and the therapeutic success of autologous HSCT-GT, the U.S. Food and Drug Administration (FDA) in 2022 approved an HSCT-GT for β-thalassemia (Zynteglo™). This review illuminates the β-globin gene research journey, adversities faced, and achievements reached; it highlights important molecular and genetic findings of the β-globin locus, describes the predominant globin vectors, and concludes by describing promising results from clinical trials for both sickle cell disease and β-thalassemia.
Topics: Humans; beta-Thalassemia; Hematopoietic Stem Cell Transplantation; Genetic Vectors; Hemoglobinopathies; Anemia, Sickle Cell; Genetic Therapy; beta-Globins
PubMed: 36992422
DOI: 10.3390/v15030713 -
International Journal of Laboratory... Sep 2022Hemoglobinopathies are the most common monogenic disorders in the world with an ever increasing global disease burden each year. As most hemoglobinopathies show... (Review)
Review
Hemoglobinopathies are the most common monogenic disorders in the world with an ever increasing global disease burden each year. As most hemoglobinopathies show recessive inheritance carriers are usually clinically silent. Programmes for preconception and antenatal carrier screening, with the option of prenatal diagnosis are considered beneficial in many endemic countries. With the development of genetic tools such as Array analysis and Next Generation Sequencing in addition to state of the art screening at the hematologic, biochemic and genetic level, have contributed to the discovery of an increasing number of rare rearrangements and novel factors influencing the disease severity over the recent years. This review summarizes the basic requirements for adequate carrier screening analysis, the importance of genotype-phenotype correlation and how this may lead to the unrevealing exceptional interactions causing a clinically more severe phenotype in otherwise asymptomatic carriers. A special group of patients are β-thalassemia carriers presenting with features of β-thalassemia intermedia of various clinical severity. The disease mechanisms may involve duplicated α-globin genes, mosaic partial Uniparental Isodisomy of chromosome 11p15.4 where the HBB gene is located or haplo-insufficiency of a non-linked gene SUPT5H on chromosome 19q, first described in two Dutch families with β-thalassemia trait without variants in the HBB gene.
Topics: Female; Genotype; Hemoglobinopathies; Humans; Nuclear Proteins; Phenotype; Pregnancy; Prenatal Diagnosis; Transcriptional Elongation Factors; alpha-Globins; beta-Thalassemia
PubMed: 36074711
DOI: 10.1111/ijlh.13885 -
Deutsches Arzteblatt International Aug 2011Hemoglobinopathies are among the most common inherited diseases around the world. They have become much more common recently in northern and central Europe, including...
BACKGROUND
Hemoglobinopathies are among the most common inherited diseases around the world. They have become much more common recently in northern and central Europe, including Germany, due to immigration.
METHOD
Selective review of the literature with consideration of national guidelines.
RESULTS
The hemoglobinopathies encompass all genetic diseases of hemoglobin. They fall into two main groups: thalassemia syndromes and structural hemoglobin variants (abnormal hemoglobins). α- and β-thalassemia are the main types of thalassemia; the main structural hemoglobin variants are HbS, HbE and HbC. There are many subtypes and combined types in each group. The highly variable clinical manifestations of the hemoglobinopathies range from mild hypochromic anemia to moderate hematological disease to severe, lifelong, transfusion-dependent anemia with multiorgan involvement. Stem-cell transplantation is the preferred treatment for the severe forms of thalassemia. Supportive, rather than curative, treatment consists of periodic blood transfusions for life, combined with iron chelation. Drugs to treat the symptoms of sickle-cell disease include analgesics, antibiotics, ACE inhibitors and hydroxyurea. Blood transfusions should be given only when strictly indicated. More than 90% of patients currently survive into adulthood. Optimally treated patients have a projected life span of 50 to 60 years.
CONCLUSION
Hemoglobinopathies are a public health issue in today's multiethnic German population. Adequate care of the affected patients requires a wide variety of diagnostic and therapeutic measures.
Topics: Blood Transfusion; Cross-Sectional Studies; Emigration and Immigration; Genetic Carrier Screening; Germany; Hemoglobin C; Hemoglobin E; Hemoglobin, Sickle; Hemoglobinopathies; Humans; Iron Chelating Agents; Palliative Care; Stem Cell Transplantation; alpha-Thalassemia; beta-Thalassemia
PubMed: 21886666
DOI: 10.3238/arztebl.2011.0532 -
European Journal of Pediatrics Jun 2023Hemoglobinopathies, including thalassemias and sickle cell disease, are the most common monogenic diseases worldwide, with estimated annual births of more than 330,000... (Review)
Review
Hemoglobinopathies, including thalassemias and sickle cell disease, are the most common monogenic diseases worldwide, with estimated annual births of more than 330,000 affected infants. Hemoglobin disorders account for about 3.4% of deaths in children under 5 years of age. The distribution of these diseases is historically linked to current or previously malaria-endemic regions; however, immigration has led to a worldwide distribution of these diseases, making them a global health problem. During the last decade, new treatment approaches and novel therapies have been proposed, some of which have the potential to change the natural history of these disorders. Indeed, the first erythroid maturation agent, luspatercept, and gene therapy have been approved for beta-thalassemia adult patients. For sickle cell disease, molecules targeting vaso-occlusion and hemoglobin S polymerization include crizanlizumab, which has been approved for patients ≥ 16 years, voxelotor approved for patients ≥ 12 years, and L-glutamine for patients older than 5 years. Conclusion: We herein present the most recent advances and future perspectives in thalassemia and sickle cell disease treatment, including new drugs, gene therapy, and gene editing, and the current clinical trial status in the pediatric populations. What is Known: • Red blood cell transfusions, iron chelation therapy and hematopoietic stem cell transplantation have been the mainstay of treatment of thalassemia patients for decades. • For sickle cell disease, until 2005, treatment strategies were mostly the same as those for thalassemia, with the option of simple transfusion or exchange transfusion. In 2007, hydroxyurea was approved for patients ≥ 2 years old. What is New: • In 2019, gene therapy with betibeglogene autotemcel (LentiGlobin BB305) was approved for TDT patients ≥ 12 years old non β0/β0 without matched sibling donor. • Starting from 2017 several new drugs, such as L-glutamine (approved only by FDA), crizanlizumab (approved by FDA and EMA for patients ≥ 16 years), and lastly voxelotor (approved by FDA and EMA for patients ≥ 12 years old).
Topics: Infant; Child; Humans; Young Adult; Child, Preschool; Glutamine; Anemia, Sickle Cell; Hemoglobinopathies; Thalassemia
PubMed: 36997768
DOI: 10.1007/s00431-023-04900-w -
International Journal of Molecular... Nov 2023Hemoglobinopathies, including β-thalassemia and sickle cell disease (SCD), are common genetic blood disorders. Endocrine disorders are frequent manifestations of organ... (Review)
Review
Hemoglobinopathies, including β-thalassemia and sickle cell disease (SCD), are common genetic blood disorders. Endocrine disorders are frequent manifestations of organ damage observed mainly in patients with β-thalassemia and rarely in SCD. Iron overload, oxidative stress-induced cellular damage, chronic anemia, and HCV infection contribute to the development of endocrinopathies in β-thalassemia. The above factors, combined with vaso-occlusive events and microcirculation defects, are crucial for endocrine dysfunction in SCD patients. These endocrinopathies include diabetes mellitus, hypothyroidism, parathyroid dysfunction, gonadal and growth failure, osteoporosis, and adrenal insufficiency, affecting the quality of life of these patients. Thus, we aim to provide current knowledge and data about the epidemiology, pathogenesis, diagnosis, and management of endocrine disorders in β-thalassemia and SCD. We conducted a comprehensive review of the literature and examined the available data, mostly using the PubMed and Medline search engines for original articles. In the era of precision medicine, more studies investigating the potential role of genetic modifiers in the development of endocrinopathies in hemoglobinopathies are essential.
Topics: Humans; Iron; beta-Thalassemia; Quality of Life; Hemoglobinopathies; Anemia, Sickle Cell; Diabetes Mellitus
PubMed: 38003451
DOI: 10.3390/ijms242216263 -
Ugeskrift For Laeger Oct 2021Hereditary anaemias are the most prevalent genetic disorders worldwide. Until recently, treatment options were mostly supportive or surgical, i.e. splenectomy. Recently,... (Review)
Review
Hereditary anaemias are the most prevalent genetic disorders worldwide. Until recently, treatment options were mostly supportive or surgical, i.e. splenectomy. Recently, several medical treatments designed for frequent haemoglobinopathies such as thalassaemia and sickle cell disease have become available, and numerous new clinical trials hold promise of many more to come. Even rare anaemias such as pyruvate kinase deficiency have promising clinical trials with targeted therapies. Together, these herald hope for future treatment options for patients living with hereditary anaemias, which is discussed in this review.
Topics: Anemia, Hemolytic, Congenital Nonspherocytic; Anemia, Sickle Cell; Hemoglobinopathies; Humans; Splenectomy; Thalassemia
PubMed: 34709160
DOI: No ID Found -
Acta Clinica Croatica Dec 2020The world is struggling to deal with the corona pandemic. Effective therapies are still awaited due to the lack of understanding of the pathophysiological mechanism of... (Review)
Review
The world is struggling to deal with the corona pandemic. Effective therapies are still awaited due to the lack of understanding of the pathophysiological mechanism of the disease. Bearing recent research and clinical observations in mind, the authors propose a novel physiological mechanism of COVID-19 and explain development of COVID-19 related acute respiratory distress syndrome (ARDS) secondary to COVID-19 related hemoglobinopathy. It is a consistent observation that the radiological picture of COVID-19 related ARDS bears more resemblance to high altitude pulmonary edema (HAPE) than typical ARDS. There has been great controversy regarding this proposed similarity. The main argument from those objecting to this comparison is that the etiology is hypoxia in case of HAPE and inflammation in COVID-19 related ARDS. We propose that considering the recent bioinformatics prediction models, COVID-19 might first infect red blood cells CD147 and cause hemoglobin damage. The resulting hypoxemia may cause pulmonary hypoxic vasoconstriction leading to HAPE-like lung lesions. The now introduced alveolar hypoxia further exaggerates hemoglobinopathy hypoxemia leading to a vicious cycle. In this review, the authors recommend laboratory experiments to prove these hypotheses. The proposed physiological mechanism has significant therapeutic implications. If proven, the authors suggest the use of exchange transfusion as adjunct therapy and development of anti-CD147 drugs.
Topics: Altitude Sickness; COVID-19; Hemoglobinopathies; Humans; Pulmonary Edema; SARS-CoV-2
PubMed: 34285445
DOI: 10.20471/acc.2020.59.04.21 -
International Journal of Molecular... May 2023Beta-hemoglobinopathies are the most common genetic disorders worldwide, caused by a wide spectrum of mutations in the β-globin locus, and associated with morbidity and... (Review)
Review
Beta-hemoglobinopathies are the most common genetic disorders worldwide, caused by a wide spectrum of mutations in the β-globin locus, and associated with morbidity and early mortality in case of patient non-adherence to supportive treatment. Allogeneic transplantation of hematopoietic stem cells (allo-HSCT) used to be the only curative option, although the indispensable need for an HLA-matched donor markedly restricted its universal application. The evolution of gene therapy approaches made possible the ex vivo delivery of a therapeutic β- or γ- globin gene into patient-derived hematopoietic stem cells followed by the transplantation of corrected cells into myeloablated patients, having led to high rates of transfusion independence (thalassemia) or complete resolution of painful crises (sickle cell disease-SCD). Hereditary persistence of fetal hemoglobin (HPFH), a syndrome characterized by increased γ-globin levels, when co-inherited with β-thalassemia or SCD, converts hemoglobinopathies to a benign condition with mild clinical phenotype. The rapid development of precise genome editing tools (ZFN, TALENs, CRISPR/Cas9) over the last decade has allowed the targeted introduction of mutations, resulting in disease-modifying outcomes. In this context, genome editing tools have successfully been used for the introduction of HPFH-like mutations both in promoters or/and in the erythroid enhancer of to increase HbF expression as an alternative curative approach for β-hemoglobinopathies. The current investigation of new HbF modulators, such as ZBTB7A, KLF-1, SOX6, and ZNF410, further expands the range of possible genome editing targets. Importantly, genome editing approaches have recently reached clinical translation in trials investigating HbF reactivation in both SCD and thalassemic patients. Showing promising outcomes, these approaches are yet to be confirmed in long-term follow-up studies.
Topics: Humans; CRISPR-Cas Systems; Cell Line, Tumor; Transcription Factors; DNA-Binding Proteins; Hemoglobinopathies; Gene Editing; Anemia, Sickle Cell; gamma-Globins; beta-Thalassemia
PubMed: 37298481
DOI: 10.3390/ijms24119527 -
Blood Cells, Molecules & Diseases May 2018
Topics: Animals; Genetic Association Studies; Genetic Predisposition to Disease; Globins; Hemoglobinopathies; Humans
PubMed: 28214138
DOI: 10.1016/j.bcmd.2017.02.002