Showing papers on "Hemoglobin A2 published in 2013"

Hemoglobin A2 Lowered by Iron Deficiency and α-Thalassemia: Should Screening Recommendation for β-Thalassemia Change?

Abstract: Screening for β-thalassemia trait (BTT) relies on measuring hemoglobin (Hb) A2. Since multiple factors can affect HbA2 levels, the screening can become unreliable. In 1356 healthy Arabs enrolled into a federally funded premarital BTT screening program, the effects of iron deficiency (ID), α+-thalassemia trait, gender, smoking, and tribalism on HbA2 were studied. The complete blood count and hemoglobin fractions were determined on the entire cohort; serum ferritin ( 3.5%). Among 77(20.3%) subjects with ID, the mean HbA2 (2.30 ± 0.23%) was 0.2% lower than in subjects without iron deficiency (2.50 ± 0.24%, P < 0.0001). In 65 (38%)/172 subjects with phenotypic α+-thalassemia trait, the mean HbA2 (2.43 ± 0.24%) was 0.13% lower than in subjects without α+-thalassemia trait, P < 0.0001. The mean HbA2 did not differ between males and females, smokers and nonsmokers, and between the tribes. Thus, 35 (2.6%) subjects with HbA2 between 3.2 and 3.5% were at a risk of false negative diagnosis of BTT. Since iron deficiency and α+-thalassemia are both common and both lower HbA2, modifications in screening recommendations for BTT are proposed.

Depression in subjects with beta-thalassemia minor

Abstract: Beta-thalassemia minor is a common genetic blood disorder in Mediterranean countries such as Turkey. Additionally, depression is one of the most widespread mental disorders that affect people worldwide, and its prevalence is increasing with co-occurring medical conditions. The aim of this study was to determine whether the frequency of depression is elevated in subjects with beta-thalassemia minor. A total of 106 subjects were included in this study, of which 53 participants were diagnosed with beta-thalassemia minor. The other 53 participants were otherwise healthy. Hemoglobin electrophoresis and a complete blood count were performed in all subjects, and all participants were evaluated using the Hamilton Depression Rating Scale (HDRS). The HDRS scores of the subjects with beta-thalassemia minor were higher than those in the healthy subjects (p < 0.001). Additionally, the hemoglobin A2 levels were positively associated with the HDRS scores (p < 0.0001, r = 0.482). This study suggests a possible association between depression and beta-thalassemia minor, in which the risk of depression may be increased in subjects with this condition.

Hematologic and Coagulation Disorders

Abstract: Normal adult hemoglobin consists of four polypeptides (two alpha chains and two beta chains) and the ironcontaining prosthetic group (heme or ferroprotoporphyrin IX). In the early embryo, theta (y) and zeta (z) chains are present instead of the alpha (a) chains, and epsilon (e) chains are present instead of the beta (b) chains. After early embryogenesis, pairs of alpha chains are linked with pairs of either beta, gamma (g), or delta (d) chains to form adult hemoglobin (Hgb A = a2b2), fetal hemoglobin (Hgb F = a2g2), or hemoglobin A2 (Hgb A2 = a2d2). By term gestation, the ratio of hemoglobin F to hemoglobin A is approximately 1:1. By 1 year of age, hemoglobin F typically constitutes less than 1% of total hemoglobin. Although hemoglobin A2 is present, it accounts for less than 2.5% of total adult hemoglobin. The sequence of amino acids (141 amino acids for alpha chains and 146 for beta chains) defines the primary structure. The three-dimensional shape of each chain defines the secondary structure, and the relationship between the four chains and the heme prosthetic group defines the tertiary structure. The binding of the ligands 2,3-diphosphoglycerate (2,3-DPG) and oxygen defines the quaternary structure. The affinity of hemoglobin for oxygen is expressed as the P50 (i.e., the oxygen tension at which half of hemoglobin’s oxygen-carrying capacity is used). Increased temperature and increases in hydrogen ion [H+] and 2,3-DPG concentrations reduce the affinity of hemoglobin for oxygen, leading to an increase in the P50 and facilitating the unloading of oxygen at peripheral tissues. In comparison with purified hemoglobin A, purified hemoglobin F has a lower oxygen affinity and a greater response to changes in pH but only a minimal response to changes in 2,3-DPG concentration. The decreased interaction between hemoglobin F and intraerythrocyte 2,3-DPG accounts for the increased affinity of fetal blood for oxygen in vivo.

Clinical characteristics of pediatric thalassemia in Korea: a single institute experience.

Abstract: Few literatures have elaborated on the clinical characteristics of children with thalassemia from low-prevalence areas. A retrospective analysis was conducted on children genetically confirmed with thalassemia at Seoul National University Children's Hospital in Korea. Nine children (1α thalassemia trait, 6β thalassemia minor, 2β thalassemia intermedia) were diagnosed with thalassemia at median age of 4.3 yr old with median hemoglobin of 9.7 g/dL. Seven (78%) children were incidentally found to be anemic and only 2 with β thalassemia intermedia had presenting symptoms. Five children (56%) were initially misdiagnosed with iron deficiency anemia. Despite the comorbidities due to α thalassemia mental retardation syndrome, the child with α thalassemia trait had mild hematologic profile. Children with β thalassemia intermedia had the worst phenotypes due to dominantly inherited mutations. None of the children was transfusion dependent and most of them had no complications associated with thalassemia. Only 1 child (11%) with codon 60 (T→A) mutation of the HBB gene needed red blood cell transfusions. He also had splenomegaly, cholelithiasis, and calvarial vault thickening. Pediatricians in Korea must acknowledge thalassemia as a possible diagnosis in children with microcytic hypochromic hemolytic anemia. High level of suspicion will allow timely diagnosis and managements.

GSTM1 and GSTT1 Polymorphism in Egyptian Sickle Cell Anemia Patients

Abstract: Glutathione S-transferase gene deletions are known detoxification agents and cause oxidative damage. In different studies, variations in null allele frequency have been observed. We have investigated the prevalence of the GSTM1 and GSTT1 null genotypes in sickle cell disease (SCD) patients. Thirty-seven sickle cell anemia and forty controls were evaluated to determine the frequency of Glutathione S-transferase (GST) gene deletions. Complete blood counts were performed by an automated cell analyzer. Hemoglobin F, hemoglobin A, hemoglobin A2 and hemoglobin S were measured and diagnosis of patients was achieved by high performance liquid chromatography. The GST null genotype was determined using polymerase chain reaction (PCR) method. The prevalence of GSTM1-null genotype in SCD was 37.8%, compared to 55.0% in the control group (OR= 0.9, 95% CI= 0.3-2.8, p= 0.24). The frequency of individuals carrying GSTT1 null genotype was higher among SCA patients (64.9%) compared to controls (42.5%) (Odds Ratio, OR= 2.5, 95% Confidence Interval, CI= 1.8-4.2, p= 0.015).Present results showed that the frequency of combined polymorphism GSTT1/M1 null genotypes were not statistically significant. GSTT1 and GSTM1 showed no statistical significance between patients and control group in relation to both clinical and laboratory findings. We have observed that GSTT1 null genotypes were high among Egyptian sickle cell anemia patients and both GSTT1 and GSTM1 null genotypes were not related to both clinical and laboratory findings in SCD patients.

Incidence of β-thalassemia carrier on 1495 couples in preconceptional period.

Abstract: Objective: This research, conducted on 1495 couples in preconceptional period, demonstrates how the study of globular resistance of erythrocytes (GRO) is not a first choice test and not useful as other more accurate tests to identify subjects with β-thalassemia trait Instead, the complete blood count (CBC) and the evaluation of HbA, HbA2 and HbF by high pressure liquid chromatography (HPLC) are essential Methods: Each couple arrived in our laboratory to screen for β thalassemia In case of patients with positive (240) or doubtful (112) results, we studied β-globin gene Results: Of the 2990 subjects examined, we found 280 subjects with β-thalassemia trait (936%) During biochemical tests, among 112 subjects with doubtful – normal GRO or altered GRO – results, 40 of them resulted positive for the molecular analysis, while 72 of them did not show mutations in β-globin genes The 2710 samples with non-carriers of β-thalassemia trait presented as mean evaluation of HbA2 26%, while the 280 subjects with β-

Hb Treviso [α91(FG3)Leu→Phe (α2)]: A New Slightly Unstable Hemoglobin Variant with Moderately Decreased Oxygen Affinity

Abstract: We report a new hemoglobin (Hb) variant, found in a North-East Italian family living in the city of Treviso. The proband, a non anemic 60-year-old male with a history of chronic rhinitis, allergy to Parietaria and suspected obstructive sleep apnea syndrome, was referred for blood gas analysis. Determination of the oxygen affinity revealed a p50 of 32.5 mmHg (control 27.5 mmHg) indicating a moderate decrease in oxygen affinity. An abnormal pattern compatible with an α Hb variant was observed on high performance liquid chromatography (HPLC); direct sequencing revealed a transition at codon 91 of the α2 gene (HBA2: c.274C>T) changing leucine into phenylalanine. Characterization and phenotype studies are reported.

Use of serum iron status and hemoglobin A2 levels for discrimination between iron deficiency and thalassemia minor.

Abstract: We read with interest the article by Nalbantoglu et al [1] In their article, it was stated that the valid formulas calculated from erythrocyte indices on automated blood counts are not sufficient