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American Family Physician Aug 2009The thalassemias are a group of inherited hematologic disorders caused by defects in the synthesis of one or more of the hemoglobin chains. Alpha thalassemia is caused... (Review)
Review
The thalassemias are a group of inherited hematologic disorders caused by defects in the synthesis of one or more of the hemoglobin chains. Alpha thalassemia is caused by reduced or absent synthesis of alpha globin chains, and beta thalassemia is caused by reduced or absent synthesis of beta globin chains. Imbalances of globin chains cause hemolysis and impair erythropoiesis. Silent carriers of alpha thalassemia and persons with alpha or beta thalassemia trait are asymptomatic and require no treatment. Alpha thalassemia intermedia, or hemoglobin H disease, causes hemolytic anemia. Alpha thalassemia major with hemoglobin Bart's usually results in fatal hydrops fetalis. Beta thalassemia major causes hemolytic anemia, poor growth, and skeletal abnormalities during infancy. Affected children will require regular lifelong blood transfusions. Beta thalassemia intermedia is less severe than beta thalassemia major and may require episodic blood transfusions. Transfusion-dependent patients will develop iron overload and require chelation therapy to remove the excess iron. Bone marrow transplants can be curative for some children with beta thalassemia major. Persons with thalassemia should be referred for preconception genetic counseling, and persons with alpha thalassemia trait should consider chorionic villus sampling to diagnose infants with hemoglobin Bart's, which increases the risk of toxemia and postpartum bleeding. Persons with the thalassemia trait have a normal life expectancy. Persons with beta thalassemia major often die from cardiac complications of iron overload by 30 years of age.
Topics: Blood Transfusion; Bone Marrow Transplantation; Chelation Therapy; Erythrocyte Indices; Erythropoiesis; Hemoglobins; Humans; alpha-Thalassemia; beta-Thalassemia
PubMed: 19678601
DOI: No ID Found -
Mediterranean Journal of Hematology and... 2019Therapeutic advances, including the availability of oral iron chelators and new non-invasive methods for early detection and treatment of iron overload, have... (Review)
Review
Therapeutic advances, including the availability of oral iron chelators and new non-invasive methods for early detection and treatment of iron overload, have significantly improved the life expectancy and quality of thalassemia patients, with a consequent increase in their reproductive potential and desire to have children. Hundreds of pregnancies have been reported so far, highlighting that women carefully managed in the preconception phase usually carry out a successful gestation and labor, both in case of spontaneous conception and assisted reproductive techniques. A multidisciplinary team including a cardiologist, an endocrinologist, and a gynecologist, under the supervision of an expert in beta-thalassemia, should be involved. During pregnancy, a close follow-up of maternal disorders and of the baby's status is recommended. Hemoglobin should be maintained over 10 g/dL to allow normal fetal growth. Chelators are not recommended; nevertheless, it may be reasonable to consider restarting chelation therapy with desferrioxamine towards the end of the second trimester when the potential benefits outweigh the potential fetal risk. Women with non-transfusion-dependent thalassemia who have never previously been transfused or who have received only minimal transfusion therapy are at risk of severe alloimmune anemia if blood transfusions are required during pregnancy. Since pregnancy increases the risk of thrombosis three-fold to four-fold and thalassemia is also a hypercoagulable state, the recommendation is to keep women who are at higher risk -such as those who are not regularly transfused and those splenectomised- on prophylaxis during pregnancy and the postpartum period.
PubMed: 30858957
DOI: 10.4084/MJHID.2019.019 -
Medicina (Kaunas, Lithuania) Oct 2022Non-transfusion-dependent thalassemia (NTDT) has been considered less severe than its transfusion-dependent variants. The most common forms of NTDT include... (Review)
Review
Non-transfusion-dependent thalassemia (NTDT) has been considered less severe than its transfusion-dependent variants. The most common forms of NTDT include β-thalassemia intermedia, hemoglobin E/beta thalassemia, and hemoglobin H disease. Patients with NTDT develop several clinical complications, despite their regular transfusion independence. Ineffective erythropoiesis, iron overload, and hypercoagulability are pathophysiological factors that lead to morbidities in these patients. Therefore, an early and accurate diagnosis of NTDT is essential to ascertaining early interventions. Currently, several conventional management options are available, with guidelines suggested by the Thalassemia International Federation, and novel therapies are being developed in light of the advancement of the understanding of this disease. This review aimed to increase clinicians' awareness of NTDT, from its basic medical definition and genetics to its pathophysiology. Specific complications to NTDT were reviewed, along with the risk factors for its development. The indications of different therapeutic options were outlined, and recent advancements were reviewed.
Topics: Humans; Blood Transfusion; Hemoglobin E; Iron Chelating Agents; Iron Overload; Thalassemia
PubMed: 36295656
DOI: 10.3390/medicina58101496 -
Haematologica Jun 2013Non-transfusion-dependent thalassemias include a variety of phenotypes that, unlike patients with beta (β)-thalassemia major, do not require regular transfusion therapy... (Review)
Review
Non-transfusion-dependent thalassemias include a variety of phenotypes that, unlike patients with beta (β)-thalassemia major, do not require regular transfusion therapy for survival. The most commonly investigated forms are β-thalassemia intermedia, hemoglobin E/β-thalassemia, and α-thalassemia intermedia (hemoglobin H disease). However, transfusion-independence in such patients is not without side effects. Ineffective erythropoiesis and peripheral hemolysis, the hallmarks of disease process, lead to a variety of subsequent pathophysiologies including iron overload and hypercoagulability that ultimately lead to a number of serious clinical morbidities. Thus, prompt and accurate diagnosis of non-transfusion-dependent thalassemia is essential to ensure early intervention. Although several management options are currently available, the need to develop more novel therapeutics is justified by recent advances in our understanding of the mechanisms of disease. Such efforts require wide international collaboration, especially since non-transfusion-dependent thalassemias are no longer bound to low- and middle-income countries but have spread to large multiethnic cities in Europe and the Americas due to continued migration.
Topics: Blood Transfusion; Gene-Environment Interaction; Humans; Phenotype; Thalassemia
PubMed: 23729725
DOI: 10.3324/haematol.2012.066845 -
International Journal of Molecular... Sep 2022Thalassemia is the most common genetic disorder worldwide. Thalassemia intermedia (TI) is non-transfusion-dependent thalassemia (NTDT), which includes β-TI hemoglobin,... (Review)
Review
Thalassemia is the most common genetic disorder worldwide. Thalassemia intermedia (TI) is non-transfusion-dependent thalassemia (NTDT), which includes β-TI hemoglobin, E/β-thalassemia and hemoglobin H (HbH) disease. Due to the availability of iron chelation therapy, the life expectancy of thalassemia major (TM) patients is now close to that of TI patients. Iron overload is noted in TI due to the increasing iron absorption from the intestine. Questions are raised regarding the relationship between iron chelation therapy and decreased patient morbidity/mortality, as well as the starting threshold for chelation therapy. Searching all the available articles up to 12 August 2022, iron-chelation-related TI was reviewed. In addition to splenectomized patients, osteoporosis was the most common morbidity among TI cases. Most study designs related to ferritin level and morbidities were cross-sectional and most were from the same Italian study groups. Intervention studies of iron chelation therapy included a subgroup of TI that required regular transfusion. Liver iron concentration (LIC) ≥ 5 mg/g/dw measured by MRI and ferritin level > 300 ng/mL were suggested as indicators to start iron chelation therapy, and iron chelation therapy was suggested to be stopped at a ferritin level ≤ 300 ng/mL. No studies showed improved overall survival rates by iron chelation therapy. TI morbidities and mortalities cannot be explained by iron overload alone. Hypoxemia and hemolysis may play a role. Head-to-head studies comparing different treatment methods, including hydroxyurea, fetal hemoglobin-inducing agents, hypertransfusion as well as iron chelation therapy are needed for TI, hopefully separating β-TI and HbH disease. In addition, the target hemoglobin level should be determined for β-TI and HbH disease.
Topics: Ferritins; Humans; Iron; Iron Chelating Agents; Iron Overload; alpha-Thalassemia; beta-Thalassemia
PubMed: 36077584
DOI: 10.3390/ijms231710189 -
Mediterranean Journal of Hematology and... 2023Hemoglobin H disease HbH, a hemoglobinopathy resulting from abnormal alpha globin genes, is classified into two categories: deletional HbH DHbH and non-deletional HbH...
BACKGROUND
Hemoglobin H disease HbH, a hemoglobinopathy resulting from abnormal alpha globin genes, is classified into two categories: deletional HbH DHbH and non-deletional HbH NDHbH. The alpha-mutation genotypes exhibit a range of clinical anemias, which differentially impact patient growth.
OBJECTIVES
This retrospective study assessed the growth of HbH patients at Siriraj Hospital, Mahidol University.
METHODS
Patients diagnosed with HbH between January 2005 and April 2021 were analyzed using growth standard scores of the Thai Society for Pediatric Endocrinology (2022 version) and BMI-for-age Z scores of the World Health Organization. Growth failure was defined as a patient's height for age exceeding two standard deviations below the mean.
RESULTS
Of the 145 HbH patients, 75 51.7 had NDHbH, with --αα being the most common genotype 70 patients; 93.3. The mean baseline hemoglobin level was significantly lower in NDHbH patients than in DHbH patients (8.16 ± 0.93 gdL vs. 9.51 ± 0.68 gdL; < 0.001. Splenomegaly and growth failure prevalences were higher in NDHbH patients (37.3 vs. 0%, with < 0.001, and 22.7% vs. 8.6%, with = 0.020, respectively). Multivariable analysis revealed splenomegaly > 3 cm was associated with growth failure (OR = 4.28; 95% CI, 1.19-15.39; = 0.026).
CONCLUSIONS
NDHbH patients exhibited lower hemoglobin levels and more pronounced splenomegaly than DHbH patients. Growth failure can occur in both HbH types but appears more prevalent in NDHbH. Close monitoring of growth velocity is essential, and early treatment interventions may be required to prevent growth failure.
PubMed: 37705526
DOI: 10.4084/MJHID.2023.045 -
Cold Spring Harbor Perspectives in... May 2013α-Thalassemia mutations affect up to 5% of the world's population. The clinical spectrum ranges from an asymptomatic condition to a fatal in utero disease. Hemoglobin H... (Review)
Review
α-Thalassemia mutations affect up to 5% of the world's population. The clinical spectrum ranges from an asymptomatic condition to a fatal in utero disease. Hemoglobin H disease results from mutations of three α-globin genes. Deletional forms result in a relatively mild anemia, whereas nondeletional mutations result in a moderate to severe disease characterized by ineffective erythropoiesis, recurrent transfusions, and growth delay. Hemosiderosis develops secondary to increased iron absorption, as well as transfusion burden. Hemoglobin Bart's hydrops fetalis is usually a fatal in utero disease caused by the absence of α genes. Population screening to identify at-risk couples is essential. Affected pregnancies result in severe fetal and maternal complications. Doppler ultrasonography with intrauterine transfusion therapy may improve the fetal prognosis but creates ethical challenges for the family and health providers.
Topics: Age of Onset; Chronic Disease; Critical Illness; Delayed Diagnosis; Female; Global Health; Heterozygote; Humans; Hydrops Fetalis; Infant, Newborn; Iron Overload; Mutation; Neonatal Screening; Pregnancy; Prenatal Diagnosis; alpha-Thalassemia
PubMed: 23543077
DOI: 10.1101/cshperspect.a011742 -
Journal of Clinical Laboratory Analysis Oct 2022Hemoglobin H (Hb H) disease is a moderate-to-severe form of α-thalassemia (α-thal), and parts of patients may require intermittent transfusion therapy, especially...
BACKGROUND
Hemoglobin H (Hb H) disease is a moderate-to-severe form of α-thalassemia (α-thal), and parts of patients may require intermittent transfusion therapy, especially during intercurrent illness. However, rare Hb H diseases remain undetected using routine methods being outside of the testing scope. In this study, we present an approach to detecting Hb H disease by long molecule sequencing (LMS).
METHODS
A total of 206 known genotype samples were collected and carried to blind detected by LMS on the PacBio Sequel platform. Circular consensus sequencing reads were aligned to the hg19 reference genome using Free-Bayes finished LMS. LMS accuracy would be compared with routine methods, including Gap-PCR and PCR-Reverse dot blot hybridization (PCR-RDB).
RESULTS
The assay could detect carriers of both deletion and point mutations. It had an overall accuracy of 100% when compared with routine methods. In addition, LMS detected six mutations based on routine methods and corrected three case results. Hb H diseases were identified using LMS, whether a common or rare genotype, a deletion or non-deletion genotype. However, two cases of Hb H disease were misdiagnosed using routine methods.
CONCLUSIONS
Long molecule sequencing can be suggested as a rapid and reliable assay to detect probable carriers of hemoglobinopathies. LMS accurately identified the common and rare genotypes of Hb H disease.
Topics: Bayes Theorem; Genotype; Hemoglobin H; Hemoglobinopathies; Humans; Mutation; alpha-Thalassemia; beta-Thalassemia
PubMed: 36059093
DOI: 10.1002/jcla.24687