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Hematology/oncology Clinics of North... Dec 2022Sickle cell disease (SCD) is a genetic hemoglobinopathy associated with extensive morbidity and early mortality. While there have been recent improvements in available... (Review)
Review
Sickle cell disease (SCD) is a genetic hemoglobinopathy associated with extensive morbidity and early mortality. While there have been recent improvements in available disease-modifying therapies for SCD, cardiopulmonary complications remain a major risk factor for death in this population. We provide an overview of current knowledge regarding several of the major acute and chronic cardiopulmonary complications in SCD, including: acute chest syndrome, airway disease, lung function abnormalities, nocturnal hypoxemia and sleep disordered breathing, pulmonary vascular disease, and sickle cell cardiomyopathy.
Topics: Humans; Anemia, Sickle Cell; Sleep Apnea Syndromes; Vascular Diseases
PubMed: 36400540
DOI: 10.1016/j.hoc.2022.07.014 -
Transfusion Clinique Et Biologique :... Nov 2019Transfusion in paediatrics requires specific guidelines, because child physiology and pathology differ significantly as compared to adults. Adverse transfusion reactions... (Review)
Review
Transfusion in paediatrics requires specific guidelines, because child physiology and pathology differ significantly as compared to adults. Adverse transfusion reactions in transfused children also vary in type and frequency, but there is a better understanding of these reactions in adults than in children. However, for the most frequent adverse transfusion reactions, the overall prevalence is higher in children than in adults, with the exception of post-transfusion red blood cell alloimmunisation, which is lower, excluding patients with haemoglobinopathies. In several studies, allergic reactions were the most frequently reported adverse transfusion reaction in paediatrics, and the platelet concentrate the most frequently implicated blood product. Early diagnosis of certain adverse transfusion reactions such as haemosiderosis, is essential in order to initiate the best therapy and obtain a good clinical outcome. The prevention of adverse transfusion reactions in children is required, but needs further clinical studies in paediatrics. Lastly, changes in technology, policy and clinical practices will improve transfusion safety in children.
Topics: Adolescent; Age Factors; Blood Component Transfusion; Blood Group Incompatibility; Child; Child, Preschool; Enterocolitis, Necrotizing; Erythrocytes; Forecasting; Graft vs Host Disease; Hemoglobinopathies; Humans; Infant; Infant, Newborn; Iron Overload; Practice Guidelines as Topic; Prevalence; Transfusion Reaction; Transfusion-Related Acute Lung Injury
PubMed: 31563446
DOI: 10.1016/j.tracli.2019.08.002 -
British Journal of Haematology Jun 2023Hyperhaemolysis syndrome (HHS), a severe form of delayed haemolytic transfusion reaction most commonly described in patients with sickle cell disease (SCD), involves... (Review)
Review
Hyperhaemolysis syndrome (HHS), a severe form of delayed haemolytic transfusion reaction most commonly described in patients with sickle cell disease (SCD), involves destruction of both donor and recipient red blood cells (RBCs). As the epidemiology and underlying pathophysiology have yet to be definitively elucidated, recognition can be challenging. We systematically reviewed PubMed and EMBASE to identify all cases of post-transfusion hyperhaemolysis and characterized the epidemiological, clinical and immunohaematological characteristics and treatments of HHS. We identified 51 patients (33 females and 18 males), including 31 patients with SCD (HbSS, HbSC and HbS/β-thalassaemia). The median haemoglobin nadir (3.9 g/dL) occurred a median of 10 days post-transfusion. 32.6% and 45.7% of patients had a negative indirect anti-globulin test and a negative direct anti-globulin test, respectively. The most common therapies included corticosteroids and intravenous immune globulin. 66.0% of patients received ≥1 supportive transfusion, which was associated with a longer median hospital stay/time to recovery (23 days vs. 15 days; p = 0.015) compared to no supportive transfusion. These findings illustrate that HHS that often results in marked anaemia 10 days post-transfusion is not restricted to patients with haemoglobinopathies, and additional transfused RBCs may be associated with a longer time-to-recovery.
Topics: Male; Female; Humans; Transfusion Reaction; Anemia, Sickle Cell; Blood Transfusion; Erythrocytes; Hemoglobin SC Disease; Syndrome
PubMed: 37074146
DOI: 10.1111/bjh.18825 -
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 -
Expert Review of Hematology Jan 2020: Hemoglobinopathies are important causes of inherited disorders with substantial mortality and morbidity across the world. Therefore, proper utilization of available... (Review)
Review
: Hemoglobinopathies are important causes of inherited disorders with substantial mortality and morbidity across the world. Therefore, proper utilization of available screening and diagnostic techniques are important for its diagnosis and management.: In this review, the authors attempt to summarize clinical presentations, give a brief account of existing techniques, and discuss evolving and advanced techniques for detection and screening of the condition. As prevention of the disease condition is an important community measure to control the disease, techniques involving newborn screening, antenatal diagnosis, and point of care tests have been described in addition to more advanced molecular and protein diagnostics. The literature search in this area is covered between 1980 and 2018 with PubMed as the main source along with authors' own research in this area.: Screening and detection of hemoglobinopathy is best accomplished by a hierarchical approach with the optimum blend of old and newer techniques. Starting with point of care techniques through the commonly used HPLC and high voltage capillary electrophoresis, or modern and high throughput molecular biology and mass spectroscopic techniques can be used depending on specific situations. Every country needs to optimize its techniques depending on the frequency of the problem and available resources.
Topics: Female; Hemoglobinopathies; Humans; Infant, Newborn; Neonatal Screening; Pregnancy; Prenatal Diagnosis
PubMed: 31432725
DOI: 10.1080/17474086.2019.1656525 -
Transfusion Clinique Et Biologique :... Sep 2019Thalassemia and sickle cell disease (SCD) are among the most common inherited diseases worldwide. Red blood cell transfusion is a cornerstone of their treatment, but its... (Review)
Review
Thalassemia and sickle cell disease (SCD) are among the most common inherited diseases worldwide. Red blood cell transfusion is a cornerstone of their treatment, but its indications have significantly changed over the past years. New therapies are emerging in both syndromes: among them, hematopoietic stem cell transplantation is now routinely proposed, and gene therapy has shown promising preliminary results.
Topics: Allografts; Anemia, Sickle Cell; Child; Emergencies; Erythrocyte Transfusion; Exchange Transfusion, Whole Blood; Genetic Therapy; Hematopoietic Stem Cell Transplantation; Hemoglobinopathies; Humans; Hydroxyurea; Multiple Organ Failure; Thalassemia
PubMed: 31300265
DOI: 10.1016/j.tracli.2019.06.323 -
Hemoglobin Jan 2022Acknowledging and understanding the extent of thalassemia and hemoglobinopathy issues in a country is crucial for the benefit of implementing a national preventive and... (Review)
Review
Acknowledging and understanding the extent of thalassemia and hemoglobinopathy issues in a country is crucial for the benefit of implementing a national preventive and control program to reduce its prevalence. In order to obtain reliable prevalence data, the gene frequencies of the thalassemias and other hemoglobinopathies should be investigated. Molecular studies on thalassemia have yet to be done for Brunei's population. It was estimated that carriers of thalassemia or hemoglobinopathies in Brunei is approximately 5.0% or less of the overall population. There are about 200 current cases of thalassemia and other hemoglobinopathies including adults and children reported across all four districts of Brunei. Blood parameter analysis, microscopy, hemoglobin (Hb) electrophoresis and high performance liquid chromatography (HPLC) are the most common methods of investigation in aiding diagnosis in the hospital laboratory. Genotyping analysis conducted in an overseas laboratory has been employed to confirm some diagnosis. Compiled data from 2009-2017 at the Hematology Laboratory of the Raja Isteri Pengiran Anak Saleha Hospital, Jalan Putera Al-Muhtadee Billah, Bandar Seri Begawan, Brunei Darussalam, showed that the most reported diagnoses are α-thalassemia (α-thal) trait, β-thalassemia (β-thal) trait, heterozygous Hb E (: c.79G>A)/β-thal, β-thal major (β-TM) and β-thal intermedia (β-TI). The data reported indicate the importance of establishing a thalassemia registry with relevant data on patients and patient outcomes as a tool for monitoring and improving patient care.
Topics: Adult; Brunei; Child; Hemoglobinopathies; Heterozygote; Humans; alpha-Thalassemia; beta-Thalassemia
PubMed: 35950589
DOI: 10.1080/03630269.2021.2008959 -
Clinical Chemistry Jul 2023
Topics: Humans; beta-Globins; Thalassemia; Mutation; Hemoglobinopathies
PubMed: 37279577
DOI: 10.1093/clinchem/hvad067 -
International Journal of Laboratory... Jun 2023Hemoglobin disorders are among the most common genetic diseases worldwide. Molecular diagnosis is helpful in cases where the diagnosis is uncertain and for genetic... (Review)
Review
Hemoglobin disorders are among the most common genetic diseases worldwide. Molecular diagnosis is helpful in cases where the diagnosis is uncertain and for genetic counseling. Protein-based diagnostic techniques are frequently adequate for initial diagnosis. Molecular genetic testing is pursued in some cases, particularly when a definitive diagnosis is not possible and especially for the purpose of assessing genetic risk for couples wanting to have children. The expertise available in the clinical hematology laboratory is essential for the diagnosis of patients with hemoglobin abnormalities. Initial diagnoses are made using protein-based techniques such as electrophoresis and chromatography. Based on these findings, genetic risk to an individual's offspring can be assessed. In the setting of β-thalassemia and other β-globin disorders, coincident α-thalassemia may be difficult to diagnose, which can have potentially serious consequences. In addition, unusual forms of β-thalassemia caused by deletions in the β-globin locus cannot be definitively characterized using standard techniques. Molecular diagnostic testing has an important role in the diagnosis of hemoglobin disorders and is important in the setting of genetic counseling. Molecular testing also has a role in prenatal diagnosis to identify fetuses affected by severe hemoglobinopathies and thalassemias.
Topics: Pregnancy; Female; Child; Humans; beta-Thalassemia; Hemoglobinopathies; alpha-Thalassemia; Prenatal Diagnosis; Molecular Diagnostic Techniques; beta-Globins
PubMed: 37211360
DOI: 10.1111/ijlh.14089 -
Molecular Therapy : the Journal of the... Mar 2023
Topics: Humans; Gene Editing; Hemoglobinopathies; CRISPR-Cas Systems
PubMed: 36803951
DOI: 10.1016/j.ymthe.2023.02.007