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Journal ArticleDOI

Hemoglobin A2 values in sickle cell disease patients quantified by high performance liquid chromatography and the influence of alpha thalassemia.

01 Sep 2015-Revista Brasileira De Hematologia E Hemoterapia (Elsevier)-Vol. 37, Iss: 5, pp 296-301

TL;DR: Hb A2 levels are elevated in patients with Hb S or Hb C, and are directly influenced by the alpha thalassemia genotypes.

Abstracta b s t r a c t Background: In sickle cell disease, the quantification of Hb A2 is important for the differential

Topics: Hemoglobin A2 (75%), Hemoglobin A (61%), Beta thalassemia (59%), Alpha-thalassemia (59%)

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Citations
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Book
01 Jan 2020
TL;DR: This book focuses on respiratory proteins, the broad hemoglobin family, as well as the molluscan and arachnid hemocyanins (and their multifunctional roles) and a number of other proteins, such as the hemerythrins; serum albumin; serum amyloid A; von Willebrand factor and its interaction with factor VIII; and C-reactive protein.
Abstract: This book focuses on respiratory proteins, the broad hemoglobin family, as well as the molluscan and arachnid hemocyanins (and their multifunctional roles). Featuring 20 chapters addressing invertebrate and vertebrate respiratory proteins, lipoproteins and other body fluid proteins, and drawing on the editors' extensive research in the field, it is a valuable addition to the Subcellular Biochemistry book series. The book covers a wide range of topics, including lipoprotein structure and lipid transport; diverse annelid, crustacean and insect defense proteins; and insect and vertebrate immune complexes. It also discusses a number of other proteins, such as the hemerythrins; serum albumin; serum amyloid A; von Willebrand factor and its interaction with factor VIII; and C-reactive protein. Given its scope, the book appeals to biologists, biomedical scientists and clinicians, as well as advanced undergraduates and postgraduates in these disciplines. Available as a printed book and also as an e-book and e-chapters, the fascinating material included is easily accessible.

18 citations


Journal ArticleDOI
TL;DR: HbA2 has a measure of unreliability in the diagnosis of β-thalassemia carriers, and can be incorrectly diagnosed as carriers.
Abstract: Introduction: Detection of β-thalassemia trait or carriers (β-TT) depends significantly on an increase in Hemoglobin A2 (HbA2) levels, which is found at low levels (<3%) in normal healthy individua...

13 citations


Journal ArticleDOI
TL;DR: Level was influenced by the genotype of -Thal, and the diagnosis of doubleheterozygous states, such as S- Thal, should be carried out care-fully, taking into consideration the limitations of the available laboratory techniques.
Abstract: level was influenced by the genotype of -Thal.conclusion, in acountry with high degree of mis-cegenation such as Brazil, not only the diagnosis of doubleheterozygous states,suchasS- Thal,butalsothediagnosisofco-inheritance of SCA with -Thal should be carried out care-fully, taking into consideration the limitations of the availablelaboratory techniques. Family studies or DNA analysis, whenpossible, are desirable to confirm the correct diagnosis.

7 citations


Book ChapterDOI
TL;DR: It is proposed that the elevation of glutathionylation of HbS within RBCs, without inducing oxidative stress, might be an effective therapeutic strategy for sickle cell anemia.
Abstract: Sickle cell hemoglobin (HbS) is an example of a genetic variant of human hemoglobin where a point mutation in the β globin gene results in substitution of glutamic acid to valine at sixth position of the β globin chain. Association between tetrameric hemoglobin molecules through noncovalent interactions between side chain residue of βVal6 and hydrophobic grooves formed by βAla70, βPhe85 and βLeu88 amino acid residues of another tetramer followed by the precipitation of the elongated polymer leads to the formation of sickle-shaped RBCs in the deoxygenated state of HbS. There are multiple non-covalent interactions between residues across intra- and inter-strands that stabilize the polymer. The clinical phenotype of sickling of RBCs manifests as sickle cell anemia, which was first documented in the year 1910 in an African patient. Although the molecular reason of the disease has been understood well over the decades of research and several treatment procedures have been explored to date, an effective therapeutic strategy for sickle cell anemia has not been discovered yet. Surprisingly, it has been observed that the oxy form of HbS and glutathionylated form of deoxy HbS inhibits polymerization. In addition to describe the residue level interactions in the HbS polymer that provides its stability, here we explain the mechanism of inhibition in the polymerization of HbS in its oxy state. Additionally, we reported the molecular insights of inhibition in the polymerization for glutathionyl HbS, a posttranslational modification of hemoglobin, even in its deoxy state. In this chapter we briefly consider the available treatment procedures of sickle cell anemia and propose that the elevation of glutathionylation of HbS within RBCs, without inducing oxidative stress, might be an effective therapeutic strategy for sickle cell anemia.

4 citations


Journal ArticleDOI
TL;DR: Participation in a distance education course on sickle cell disease had a positive impact on the acquisition of knowledge about the disease by professional healthcare providers.
Abstract: Objective To assess the impact of the distance education course “Sickle Cell Disease: Primary Health Care Line” on knowledge acquisition of professional healthcare providers. Methods A cross-sectional study was conducted with a quantitative approach at the Educational and Support Center for Hemoglobinopathies (Cehmob-MG), state of Minas Gerais, Brazil, in 2016. One hundred and fifty-three out of 300 professional healthcare providers were invited to participate in the proposed distance course. Of the participating professional healthcare providers, 72 (47%) successfully concluded the course (Group A), whereas 81 (53%) did not complete their course assignments and did not meet the minimum requirements for regular attendance (Group B). Knowledge acquisition was assessed with the Knowledge of Sickle Cell Disease Instrument, DFConhecimento, applied using the web tool eSurv. Univariate analysis by Poisson regression was employed to assess the influence of sociodemographic variables on the DFConhecimento score and to select variables to compose the initial multivariate regression model (p-value Results The average score was 9.76 for Group A and 6.54 for Group B. The two groups were considered statistically different (p-value Conclusion Participation in a distance education course on sickle cell disease had a positive impact on the acquisition of knowledge about the disease by professional healthcare providers.

3 citations


References
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Journal ArticleDOI
TL;DR: This work discusses EWAS design, cohort and sample selections, statistical significance and power, confounding factors and follow-up studies, and how integration of EWASs with GWASs can help to dissect complex GWAS haplotypes for functional analysis.
Abstract: Despite the success of genome-wide association studies (GWASs) in identifying loci associated with common diseases, a substantial proportion of the causality remains unexplained. Recent advances in genomic technologies have placed us in a position to initiate large-scale studies of human disease-associated epigenetic variation, specifically variation in DNA methylation. Such epigenome-wide association studies (EWASs) present novel opportunities but also create new challenges that are not encountered in GWASs. We discuss EWAS design, cohort and sample selections, statistical significance and power, confounding factors and follow-up studies. We also discuss how integration of EWASs with GWASs can help to dissect complex GWAS haplotypes for functional analysis.

1,055 citations


Journal ArticleDOI
TL;DR: It takes considerable time to establish expertise in developing programmes for the control and management of these conditions, and the lessons learned in developed countries will need to be transmitted to those countries in which they occur at a high frequency.
Abstract: Despite major advances in our understanding of the molecular pathology, pathophysiology, and control and management of the inherited disorders of haemoglobin, thousands of infants and children with these diseases are dying through lack of appropriate medical care. This problem will undoubtedly increase over the next 20 years because, as the result of a reduction in childhood mortality due to infection and malnutrition, more babies with haemoglobin disorders will survive to present for treatment. Although WHO and various voluntary agencies have tried to disseminate information about these diseases, they are rarely mentioned as being sufficiently important to be included in setting health care priorities for the future. It takes considerable time to establish expertise in developing programmes for the control and management of these conditions, and the lessons learned in developed countries will need to be transmitted to those countries in which they occur at a high frequency.

1,051 citations


Journal ArticleDOI
03 Jun 2010-Blood
TL;DR: It is estimated that in excess of 300,000 children are born each year with a severe inherited disorder of hemoglobin and that approximately 80% of these births occur in low- or middle-income countries, with the true magnitude of this burden still unknown.
Abstract: It is estimated that in excess of 300 000 children are born each year with a severe inherited disorder of hemoglobin and that approximately 80% of these births occur in low- or middle-income countries. As these countries go through an epidemiologic transition, with a reduction in childhood and infant mortality due to improved public health measures, babies who would have previously died of these diseases before they were recognized are now surviving to present for diagnosis and treatment. Hence, they are presenting an increasing global health burden. Because of their uneven distribution in high-frequency populations, reflecting their complex population genetics, the true magnitude of this burden is still unknown. In many poor countries there are virtually no facilities for the diagnosis and management of these conditions, and even in richer countries there are limited data about their frequency, clinical course, or mortality. Without this information, it will be impossible to persuade governments about the increasing importance of these diseases. The situation will only be improved by concerted action on the part of the hematology community of the richer countries together with input from the major international health organizations and funding agencies.

615 citations


"Hemoglobin A2 values in sickle cell..." refers background in this paper

  • ...Hb A2 values were categorized in three groups based on standard reference values: (1) below 2....

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Book
17 Aug 2009
TL;DR: Current and developing approaches to treatment are incorporated, incorporating new agents for iron chelation, methods to induce fetal hemoglobin production, novel treatment approaches, stem cell transplantation, and progress in gene therapy.
Abstract: This book is a completely revised new edition of the definitive reference on disorders of hemoglobin. Authored by world-renowned experts, the book focuses on basic science aspects and clinical features of hemoglobinopathies, covering diagnosis, treatment, and future applications of current research. While the second edition continues to address the important molecular, cellular, and genetic components, coverage of clinical issues has been significantly expanded, and there is more practical emphasis on diagnosis and management throughout. The book opens with a review of the scientific underpinnings. Pathophysiology of common hemoglobin disorders is discussed next in an entirely new section devoted to vascular biology, the erythrocyte membrane, nitric oxide biology, and hemolysis. Four sections deal with α and β thalassemia, sickle cell disease, and related conditions, followed by special topics. The second edition concludes with current and developing approaches to treatment, incorporating new agents for iron chelation, methods to induce fetal hemoglobin production, novel treatment approaches, stem cell transplantation, and progress in gene therapy.

380 citations


Journal ArticleDOI
TL;DR: The availability of HPLC has streamlined many of these requirements, allowing an efficient stepwise diagnostic strategy for these complex disorders, and several guidelines have been published that outline the required steps for hemoglobinopathy and thalassemia investigation.
Abstract: Structural hemoglobin (Hb) variants typically are based on a point mutation in a globin gene that produce a single amino acid substitution in a globin chain. Although most are of limited clinical significance, a few important subtypes have been identified with some frequency. Homozygous Hb C and Hb S (sickle cell disease) produce significant clinical manifestations, whereas Hb E and Hb D homozygotes may be mildly symptomatic. Although heterozygotes for these variants are typically asymptomatic, diagnosis may be important for genetic counseling. Thalassemia, in contrast, results from quantitative reductions in globin chain synthesis. Those with diminished β-globin chains are termed β-thalassemias, whereas those with decreased α-chain production are called α-thalassemias. Severity of clinical manifestations in these disorders relates to the amount of globin chain produced and the stability of residual chains present in excess. The thalassemia minor syndromes are characterized clinically by mild anemia with persistent microcytosis. Thalassemia intermedia (i.e., Hb H disease) is typified by a moderate, variably compensated hemolytic anemia that may present with clinical symptoms during a period of physiologic stress such as infection, pregnancy, or surgery. The thalassemia major syndromes produce severe, life-threatening anemia. α-Thalassemia major usually is incompatible with extrauterine life; β-thalassemia major presents in infancy and requires life-long transfusion therapy and/or bone marrow transplantation for successful control of the disease. Double heterozygosity for certain structural variants and/or thalassemia syndromes may also lead to severe clinical disease. Several guidelines have been published that outline the required steps for hemoglobinopathy and thalassemia investigation. The availability of HPLC has streamlined many of these requirements, allowing an efficient stepwise diagnostic strategy for these complex disorders.

321 citations