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Clinica Chimica Acta; International... May 2020Iron deficiency leads to the suppression of hemoglobin (Hb) synthesis and induces metabolic disorders. In contrast, iron overload not only reduces the iron utilization... (Review)
Review
Iron deficiency leads to the suppression of hemoglobin (Hb) synthesis and induces metabolic disorders. In contrast, iron overload not only reduces the iron utilization efficiency but also induces oxidative stress. Iron metabolism in the body is closely regulated by hepcidin, a short peptide produced by the liver. Unfortunately, conventional iron indices may not always accurately reflect the iron status. For example, Hb concentration assessed using mature erythrocytes do not accurately reflect the real-time iron status due to their long lifespan. Reticulocytes are differentiated from erythroblasts after Hb synthesis and transform into mature erythrocytes in 1-2 days upon release into peripheral blood. Thus, Hb content in reticulocytes (Hb-ret) is more reflective of real-time Hb synthesis. Moreover, Hb-ret is affected only by the amount of iron intake as long as there is no hematopoietic disorder. Reticulocyte Hb content (CHr) can be accurately and inexpensively measured as Hb-ret by commercial H*3 or ADVIA hematology analyzers. CHr has been shown to be more effective than other indices of iron metabolism for the diagnosis of iron deficiency, for early detection of the therapeutic effects of iron therapy, and for differentiation of the beta thalassemia trait.
Topics: Anemia, Iron-Deficiency; Hemoglobins; Humans; Iron; Reticulocytes; beta-Thalassemia
PubMed: 32014518
DOI: 10.1016/j.cca.2020.01.032 -
Orphanet Journal of Rare Diseases May 2010Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost... (Review)
Review
Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost asymptomatic to a lethal haemolytic anaemia.It is probably the most common monogenic gene disorder in the world and is especially frequent in Mediterranean countries, South-East Asia, Africa, the Middle East and in the Indian subcontinent. During the last few decades the incidence of alpha thalassaemia in North-European countries and Northern America has increased because of demographic changes. Compound heterozygotes and some homozygotes have a moderate to severe form of alpha thalassaemia called HbH disease. Hb Bart's hydrops foetalis is a lethal form in which no alpha-globin is synthesized. Alpha thalassaemia most frequently results from deletion of one or both alpha genes from the chromosome and can be classified according to its genotype/phenotype correlation. The normal complement of four functional alpha-globin genes may be decreased by 1, 2, 3 or all 4 copies of the genes, explaining the clinical variation and increasing severity of the disease. All affected individuals have a variable degree of anaemia (low Hb), reduced mean corpuscular haemoglobin (MCH/pg), reduced mean corpuscular volume (MCV/fl) and a normal/slightly reduced level of HbA2. Molecular analysis is usually required to confirm the haematological observations (especially in silent alpha-thalassaemia and alpha-thalassaemia trait). The predominant features in HbH disease are anaemia with variable amounts of HbH (0.8-40%). The type of mutation influences the clinical severity of HbH disease. The distinguishing features of the haemoglobin Bart's hydrops foetalis syndrome are the presence of Hb Bart's and the total absence of HbF. The mode of transmission of alpha thalassaemia is autosomal recessive. Genetic counselling is offered to couples at risk for HbH disease or haemoglobin Bart's Hydrops Foetalis Syndrome. Carriers of alpha+- or alpha0-thalassaemia alleles generally do not need treatment. HbH patients may require intermittent transfusion therapy especially during intercurrent illness. Most pregnancies in which the foetus is known to have the haemoglobin Bart's hydrops foetalis syndrome are terminated due to the increased risk of both maternal and foetal morbidity.
Topics: Gene Deletion; Hemoglobins, Abnormal; Humans; Mutation; alpha-Globins; alpha-Thalassemia
PubMed: 20507641
DOI: 10.1186/1750-1172-5-13 -
The Journal of Infectious Diseases Dec 2015Hemoglobin C trait, like hemoglobin S trait, protects against severe malaria in children, but it is unclear whether hemoglobin C trait also protects against...
BACKGROUND
Hemoglobin C trait, like hemoglobin S trait, protects against severe malaria in children, but it is unclear whether hemoglobin C trait also protects against uncomplicated malaria. We hypothesized that Malian children with hemoglobin C trait would have a lower risk of clinical malaria than children with hemoglobin AA.
METHODS
Three hundred children aged 0-6 years were enrolled in a cohort study of malaria incidence in Bandiagara, Mali, with continuous passive and monthly active follow-up from June 2009 to June 2010.
RESULTS
Compared to hemoglobin AA children (n = 242), hemoglobin AC children (n = 39) had a longer time to first clinical malaria episode (hazard ratio [HR], 0.19; P = .001; 364 median malaria-free days vs 181 days), fewer episodes of clinical malaria, and a lower cumulative parasite burden. Similarly, hemoglobin AS children (n = 14) had a longer time to first clinical malaria episode than hemoglobin AA children (HR, 0.15; P = .015; 364 median malaria-free days vs 181 days), but experienced the most asymptomatic malaria infections of any group.
CONCLUSIONS
Both hemoglobin C and S traits exerted a protective effect against clinical malaria episodes, but appeared to do so by mechanisms that differentially affect the response to infecting malaria parasites.
Topics: Child; Child, Preschool; Cohort Studies; Female; Genetic Predisposition to Disease; Hemoglobin C; Hemoglobin, Sickle; Humans; Incidence; Infant; Infant, Newborn; Malaria, Falciparum; Male; Mali
PubMed: 26019283
DOI: 10.1093/infdis/jiv308 -
Journal of Diabetes and Its... Jul 2022A high hemoglobin glycation index (HGI) has been repeatedly associated with greater risk for hypoglycemia in people with diabetes and greater risk for chronic vascular... (Review)
Review
A high hemoglobin glycation index (HGI) has been repeatedly associated with greater risk for hypoglycemia in people with diabetes and greater risk for chronic vascular disease in people with or without diabetes. This review explores how different sources of analytical and biological variation in HbA1c and blood glucose individually and collectively affect the clinical information value of HGI. We conclude that HGI is a complex quantitative trait that is a clinically practical biomarker of risk for both hypoglycemia and chronic vascular disease.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Hemoglobins; Humans; Hypoglycemia; Vascular Diseases
PubMed: 35667965
DOI: 10.1016/j.jdiacomp.2022.108223 -
Clinical Biochemistry Aug 2023Hemoglobinopathies include thalassemia syndromes, where production of one or more globin subunits of hemoglobin (Hb) is reduced, and structural Hb variants. Over 1000...
BACKGROUND
Hemoglobinopathies include thalassemia syndromes, where production of one or more globin subunits of hemoglobin (Hb) is reduced, and structural Hb variants. Over 1000 disorders of Hb synthesis and/or structure have been identified and characterized, with phenotypes ranging from having severe clinical manifestations to clinically silent. Various analytical methods are used to phenotypically detect Hb variants. However, molecular genetic analysis is a more definitive method for Hb variant identification.
CASE REPORT
Here, we report a case of a 23-month-old male with results from capillary electrophoresis, gel electrophoresis (acid and alkaline), and high-performance liquid chromatography most consistent with HbS trait. Specifically, capillary electrophoresis showed slightly elevated HbF and HbA2, HbA of 39.4% and HbS of 48.5%. The HbS percentage was consistently higher than expected (typically 30-40%) for HbS trait with no concurrent thalassemic indices. The patient has not experienced any clinical complications due to the hemoglobinopathy and he is thriving.
CONCLUSION
Molecular genetic analysis revealed the presence of compound heterozygosity for HbS and Hb Olupona. Hb Olupona is an extremely rare beta-chain variant that appears as HbA on all three common methods used for phenotypic Hb analysis. When the fractional concentration of Hb variants is unusual, more definitive methods should be used, such as mass spectrometry or molecular genetic testing. In this case, incorrectly reporting this result as HbS trait is unlikely to have a significant clinical impact, as current evidence suggests Hb Olupona is not a clinically significant variant.
Topics: Male; Humans; Hemoglobins, Abnormal; Hemoglobinopathies; Thalassemia; Hemoglobin A2; Electrophoresis, Capillary
PubMed: 37236295
DOI: 10.1016/j.clinbiochem.2023.110589 -
MSphere Oct 2021Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening falciparum malaria in African children. Despite this clear protection,...
Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening falciparum malaria in African children. Despite this clear protection, the molecular mechanisms by which HbAS confers these protective phenotypes remain incompletely understood. As a forward genetic screen for aberrant parasite transcriptional responses associated with parasite neutralization in HbAS red blood cells (RBCs), we performed comparative transcriptomic analyses of Plasmodium falciparum in normal (HbAA) and HbAS erythrocytes during both cultivation of reference parasite strains and naturally occurring P. falciparum infections in Malian children with HbAA or HbAS. During cultivation, parasites matured normally in HbAS RBCs, and the temporal expression was largely unperturbed of the highly ordered transcriptional program that underlies the parasite's maturation throughout the intraerythrocytic development cycle (IDC). However, differential expression analysis identified hundreds of transcripts aberrantly expressed in HbAS, largely occurring late in the IDC. Surprisingly, transcripts encoding members of the Maurer's clefts were overexpressed in HbAS despite impaired parasite protein export in these RBCs, while parasites in HbAS RBCs underexpressed transcripts associated with the endoplasmic reticulum and those encoding serine repeat antigen proteases that promote parasite egress. Analyses of P. falciparum transcriptomes from 32 children with uncomplicated malaria identified stage-specific differential expression: among infections composed of ring-stage parasites, only cyclophilin 19B was underexpressed in children with HbAS, while trophozoite-stage infections identified a range of differentially expressed transcripts, including downregulation in HbAS of several transcripts associated with severe malaria in collateral studies. Collectively, our comparative transcriptomic screen and indicates that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Because HbAS consistently protects from severe P. falciparum, modulation of these responses may offer avenues by which to neutralize P. falciparum parasites. Sickle-trait hemoglobin (HbAS) confers nearly complete protection from severe, life-threatening malaria, yet the molecular mechanisms that underlie HbAS protection from severe malaria remain incompletely understood. Here, we used transcriptome sequencing (RNA-seq) to measure the impact of HbAS on the blood-stage transcriptome of Plasmodium falciparum in time series experiments and samples from natural infections. Our time series data reveal that, during its blood stage, P. falciparum gene expression in HbAS is impacted primarily through alterations in the abundance of gene products as opposed to variations in the timing of gene expression. Collectively, our and data indicate that P. falciparum adapts to HbAS by altering its protein chaperone and folding machinery, oxidative stress response, and protein export machinery. Due to the persistent association of HbAS and protection from severe disease, these processes that are modified in HbAS may offer strategies to neutralize P. falciparum.
Topics: Adolescent; Child; Child, Preschool; Female; Hemoglobin A; Hemoglobin, Sickle; Hemoglobins; Humans; Malaria, Falciparum; Male; Plasmodium falciparum; Sickle Cell Trait; Transcriptional Activation
PubMed: 34668757
DOI: 10.1128/mSphere.00755-21 -
Molecular Aspects of Medicine Apr 2022In mammals and other air-breathing vertebrates that live at high altitude, adjustments in convective O transport via changes in blood hemoglobin (Hb) content and/or Hb-O... (Review)
Review
In mammals and other air-breathing vertebrates that live at high altitude, adjustments in convective O transport via changes in blood hemoglobin (Hb) content and/or Hb-O affinity can potentially mitigate the effects of arterial hypoxemia. However, there are conflicting views about the optimal values of such traits in hypoxia, partly due to the intriguing observation that hypoxia-induced acclimatization responses in humans and other predominantly lowland mammals are frequently not aligned in the same direction as evolved phenotypic changes in high-altitude natives. Here we review relevant theoretical and empirical results and we highlight experimental studies of rodents and humans that provide insights into the combination of hematological changes that help attenuate the decline in aerobic performance in hypoxia. For a given severity of hypoxia, experimental results suggest that optimal values for hematological traits are conditional on the states of other interrelated phenotypes that govern different steps in the O-transport pathway.
Topics: Acclimatization; Altitude; Animals; Hemoglobins; Humans; Hypoxia; Oxygen; Oxygen Consumption
PubMed: 34879970
DOI: 10.1016/j.mam.2021.101052 -
Blood Advances May 2019The health effects of sickle cell trait among children are unknown. We compared select health outcomes and health services utilization among children with sickle cell...
The health effects of sickle cell trait among children are unknown. We compared select health outcomes and health services utilization among children with sickle cell trait, sickle cell anemia (SCA), and normal hemoglobin. Newborn screening records were used to identify children with sickle cell trait and SCA born in Michigan (1997-2014) who were enrolled in Michigan Medicaid for ≥1 year from 2012 to 2014. Each select health outcome (acute otitis media, acute respiratory infections, fever, invasive pneumococcal disease, pneumonia and influenza, renal complications, spleen problems, stroke) was defined as ≥1 claim with a diagnosis code for the respective outcome within a study year. Health services utilization was summarized as counts of emergency department, inpatient, and outpatient encounters. The relationship between hemoglobin status and each health outcome or utilization was assessed by logistic or negative binomial regression with generalized estimating equations. The study population consisted of 18 257 children with sickle cell trait, 368 with SCA, and 74 523 with normal hemoglobin (227 188 total person-years). Compared with those with normal hemoglobin, children with sickle cell trait had lower odds of acute otitis media (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.84-0.91), acute respiratory infections (OR, 0.94; 95% CI, 0.92-0.97), pneumonia and influenza (OR, 0.93; 95% CI, 0.87-0.99), and outpatient visits (incidence rate ratio, 0.95; 95% CI, 0.93-0.97). Children with SCA had higher or nonsignificant odds of all outcomes and types of health services utilization. These results indicate that children with sickle cell trait may not be at additional health risk for these outcomes. However, additional case-control studies may be necessary to identify rare events.
Topics: Adolescent; Anemia, Sickle Cell; Child; Child, Preschool; Female; Hemoglobins; Humans; Infant; Infant, Newborn; Male; Middle Aged; Sickle Cell Trait
PubMed: 31101648
DOI: 10.1182/bloodadvances.2018028043 -
Pediatric Hematology and Oncology Feb 2013Thalassemia is one of the most common hereditary disorders in Turkey. The aim of our study was to determine the prevalence of the β-thalassemia trait and abnormal...
BACKGROUND/AIMS
Thalassemia is one of the most common hereditary disorders in Turkey. The aim of our study was to determine the prevalence of the β-thalassemia trait and abnormal hemoglobin in couples who applied for premarital screening in the third largest Turkish province of Izmir in the Aegean region.
METHODS
From January 2011 to March 2012, we tested 19,277 couples at the Karşıyaka Public Health Laboratory, Thalassemia Unit for the β-thalassemia trait and abnormal hemoglobin using a high-performance liquid chromatograph, a hematology analyzer.
RESULTS
The β-thalassemia trait with increased HbA2 (>3.5%) and abnormal hemoglobin was found in 4.96% (1912/38,554) and 0.53% (206/38,554) people, respectively. Of abnormal hemoglobin findings, HbS was determined in 128 people (0.33%), HbD in 50 (0.13%), HbE in 24 (0.06%), and HbC in four (0.01%). Furthermore, in 20 of the 19,277 couples (0.05%), both partners had the β-thalassemia trait and were referred to counseling.
CONCLUSION
The prevalence of the β-thalassemia trait in the province of Izmir is high compared with other cities of Turkey. Izmir is a high-risk province for β-thalassemia and sickle-cell anemia. Therefore, premarital screening is essential to prevent new hereditary hemoglobinopaties.
Topics: Chromatography, High Pressure Liquid; Hemoglobins; Humans; Premarital Examinations; Turkey; beta-Thalassemia
PubMed: 23153313
DOI: 10.3109/08880018.2012.742604 -
International Journal of Laboratory... Aug 2022
Topics: Genotype; Hemoglobins, Abnormal; Humans; Mutation; beta-Globins; beta-Thalassemia
PubMed: 35266307
DOI: 10.1111/ijlh.13821