Hemoglobin A Research Articles

Factors affecting the evaluation and use of a hemoglobin A2 method – Lot-to-lot variation, long-term deviation and carry-over

BackgroundWe compared two Hb A2 methods, high pressure liquid chromatography and capillary zone electrophoresis, at two occasions. In 2014 the methods showed good agreement, while in 2020 HPLC results were clearly higher than CE results. This finding prompted us to investigate the external quality assessment (EQA) outcome and our total patient results obtained by high pressure liquid chromatography over several years. MethodsThe methods compared were Bio-Rad Variant II Beta-Thal Short Program (HPLC) and Sebia Capilllarys Flex Piercing (CE). ResultsOur annual patient results obtained by HPLC increased significantly from 2014 to 2020. A similar trend was also seen in our EQA results. When patient results were grouped according to different reagent lots it became evident that method comparisons might be severely affected by lot-to-lot variation. We also noticed that samples analyzed with the HPLC method following a sample containing a high proportion of Hb E where prone to give falsely increased Hb A2 results. ConclusionStandardization of the measurement of Hb A2 is urgently needed. Furthermore, the lot-to-lot variation must be minimized. While waiting for these improvements each laboratory ought to repeatedly evaluate their distribution of patient Hb A2 results.

Identification and Functional Analysis of Known and New Mutations in the Transcription Factor KLF1 Linked with β-Thalassemia-like Phenotypes.

The erythroid transcriptional factor Krüppel-like factor 1 (KLF1) is a master regulator of erythropoiesis. Mutations that cause KLF1 haploinsufficiency have been linked to increased fetal hemoglobin (HbF) and hemoglobin A2 (HbA2) levels with ameliorative effects on the severity of β-thalassemia. With the aim of determining if KLF1 gene variations might play a role in the modulation of β-thalassemia, in this study we screened 17 subjects showing a β-thalassemia-like phenotype with a slight or marked increase in HbA2 and HbF levels. Overall, seven KLF1 gene variants were identified, of which two were novel. Functional studies were performed in K562 cells to clarify the pathogenic significance of these mutations. Our study confirmed the ameliorative effect on the thalassemia phenotype for some of these variants but also raised the notion that certain mutations may have deteriorating effects by increasing KLF1 expression levels or enhancing its transcriptional activity. Our results indicate that functional studies are required to evaluate the possible effects of KLF1 mutations, particularly in the case of the co-existence of two or more mutations that could differently contribute to KLF1 expression or transcriptional activity and consequently to the thalassemia phenotype.

AGEs-RAGE-KCa3.1 pathway mediates palmitic acid-induced migration of PBMCs from patients with type 2 diabetes

Type 2 diabetes mellitus (T2DM) is characterized by chronic low-grade systemic inflammation. Tissue infiltration by monocyte migration contributes to the pathogenesis of vascular complications in T2DM. We studied the role of intermediate-conductance Ca2+-activated K+ (KCa3.1) channels in the palmitic acid (PA)-induced migration of peripheral blood mononuclear cells (PBMCs) from T2DM patients and the influence of advanced glycation endproducts (AGEs). A total of 49 T2DM patients and 33 healthy subjects was recruited into this study. Using flow cytometry and Western blotting analysis as well as cell migration assay, we found that there was a significant decrease in frequency of T lymphocytes and monocytes in CD45+ leukocyte population. PA at 100 μM stimulated migration of PBMCs from T2DM individuals, which was inhibited by the specific KCa3.1 channel blocker TRAM-34 (1 μM). The PBMC migration was positively correlated with glycosylated hemoglobin A1 chain (HbA1c) level of T2DM patients, an indicator of AGEs, and PBMCs with higher level of HbA1c showed upregulated expression of toll-like receptor (TLR) 2/4 and KCa3.1 channels. In THP-1 cells, AGEs at 200 μg/ml increased protein expression of TLR 2/4 and KCa3.1 channels, and were synergistically involved in PA-induced migration through receptors of AGEs (RAGE)-mediated KCa3.1 upregulation. In conclusion, in PBMCs of T2DM patients, AGEs promotes PA-induced migration via upregulation of TLR2/4 and KCa3.1 channels.

Identification of a Novel 7-bp Deletion in the α-Globin Gene Cluster in One Chinese Family

Deletional α-thalassemia is characterized by reduced hemoglobin A2 and involves the deletion of a few nucleotides, which is a rare hereditary disease. However, the detection of rare mutations using commonly used genetic tests is highly challenging. In the present study, next-generation sequencing (NGS) was used to identify a novel 7-bp deletion α-thalassemia in one individual from a Chinese family. Hematological parameters of the family members were determined using an automated cell counter, and hemoglobin electrophoresis was performed using a capillary electrophoresis system. Subsequently, NGS was performed on the genomic DNA of the patient and her family members. The 7-bp deletion (named Hb Honghe [HBA1: c.401_407delGCACCGT]) of α-thalassemia in the α-globin gene was confirmed using Sanger sequencing. The patient’s father was also a heterozygous carrier of HBA1: c.401_407delGCACCGT deletion, but not her mother or sister. The application of the combined molecular approach is essential for the accurate diagnosis of rare thalassemia. This study reports a novel case of α- thalassemia. The characterization of the mutation might provide new insights into genetic counseling and accurate diagnosis of thalassemia.

Abstract P321: Prevalence of Hypertension Among People Diagnosed With Diabetes in Africa, a Systematic Review and Meta-Analysis

Background: Hypertension (HTN) and diabetes (DM) share common pathophysiological mechanisms and hence have a high likelihood of co-occurring. The co-existence of HTN and DM increase increases CVD risk and exponentially increases health spending. Little is known about the burden of HTN in people with DM in Africa. Objective: To estimate the pooled prevalence of HTN in people with DM in African countries. Methods: This review was registered in the International Prospective Register of Systematic Reviews. We searched PubMed, Embase, and Hinari databases to identify peer-reviewed articles which provided data on the prevalence of HTN in people diagnosed with DM in Africa. We included studies that defined DM diagnosis as hemoglobin A1(HbA1c) >7.0 and HTN diagnosis as BP≥140/90mmHg. We quantified the prevalence of HTN using random-effects models. We applied generalized linear mixed models with logit transformation to compute regional and overall pooled prevalence and estimated heterogeneity (I 2 ). Results: Out of 3810 studies retrieved from the databases, 27 met the inclusion criteria with sample size between (80 - 4122). The mean age was 58 (± 11) years and 56% were women. The pool prevalence of HTN in people diagnosed with DM was 59.8% [95% CI: 52.8% - 66.5%]. By African region, Central Africa recorded the highest 77.6% [95% CI: 53.01% - 91.4%], South Africa 74.5% [95% CI: 67.4% - 80.5%], North Africa 65.5% [95% CI: 54.7% - 75.0%], West Africa 55.7% [95% CI: 44.0% - 66.7%] and East Africa 50.7% [95% CI: 43.7% - 57.3%]. Increasing age, being overweight/obese, being employed, longer duration of DM, urban residence, and male sex were associated with a higher likelihood of HTN diagnosis. Conclusion: The high prevalence of HTN among people with DM in Africa, supports an integrated differentiated service delivery to improve primary healthcare-level cardiovascular disease response mechanisms. The data generated from this review may inform the delivery of interventions to avert premature cardiovascular disease mortality among Africans.

The clinical and epidemiological characteristics of a series of patients living with HIV admitted for COVID-19 in a district hospital

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic continues to evolve. Globally, COVID-19 continues to strain even the most resilient healthcare systems, with Omicron being the latest variant. We made a thorough search for literature describing the effects of the COVID-19 in a high human immunodeficiency virus (HIV)/tuberculosis (TB) burden district-level hospital setting. We found scanty literature.MethodsA retrospective observational study was conducted at Khayelitsha District Hospital in Cape Town, South Africa (SA) over the period March 2020–December 2021. We included confirmed COVID-19 cases with HIV infection aged from 18 years and above. Analysis was performed to identify predictors of mortality or hospital discharge among people living with HIV (PLWH). Predictors investigated include CD4 count, antiretroviral therapy (ART), TB, non-communicable diseases, haematological, and biochemical parameters.FindingsThis cohort of PLWH with SARS-CoV-2 infection had a median (IQR) age of 46 (37–54) years, male sex distribution of 29.1%, and a median (IQR) CD4 count of 267 (141–457) cells/mm3. Of 255 patients, 195 (76%) patients were discharged, 60 (24%) patients died. One hundred and sixty-nine patients (88%) were on ART with 73(28%) patients having acquired immunodeficiency syndrome (AIDS). After multivariable analysis, smoking (risk ratio [RR]: 2.86 (1.75–4.69)), neutrophilia [RR]: 1.024 (1.01–1.03), and glycated haemoglobin A1 (HbA1c) [RR]: 1.01 (1.007–1.01) were associated with mortality.ConclusionThe district hospital had a high COVID-19 mortality rate among PLWH. Easy-to-access biomarkers such as CRP, neutrophilia, and HbA1c may play a significant role in informing clinical management to prevent high mortality due to COVID-19 in PLWH at the district-level hospitals.

The potential role of vitamin E in patients with glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis.

As an antioxidant, vitamin E (VitE) may benefit the erythrocytes by protecting glutathione from oxidation by free radicals and peroxide-generating processes. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines when reporting this systematic review. We searched 6 electronic databases (PubMed, Scopus, Web of Science, and Cochrane Library) until May 8, 2022. We included all relevant studies. According to the study design, the Cochrane assessment tool (Risk of Bias 2), Risk Of Bias In Non-randomized Studies - of Interventions checklists, and National Institutes of Health tools were used to assess the risk of bias.Continuous data were pooled as a mean difference (MD) with a relative 95% confidence interval. The protocol was registered on PROSPERO (CRD42022333848). Six studies were included in the meta-analysis with a total of 181 patients. Compared with the control group, VitE significantly improved the hemoglobin level for chronic hemolysis (MD = 2.72 g/dL, P < .0001) and for acute hemolysis (MD = 1.18 g/dL, P < .0001). It also decreased the reticulocyte level for chronic hemolysis (MD = -1.39 P < .0001) and for acute hemolysis (MD = -1.42%, P < .0001). For before and after studies, the use of VitE significantly improved the level of packed cell volume (MD = 0.56%, P < .00001), red blood cell half-life (MD = 2.19 days, P < .0001), and decreased the reticulocytes level (MD = -1.41%, P < .00001). Among patients with glucose-6-phosphate dehydrogenase deficiency, VitE might provide benefits such as increasing the hemoglobin, packed cell volume levels, red blood cell half-life, and decreasing the reticulocyte level, so reducing hemolysis. Further high-quality, well-designed randomized controlled trials are recommended.

Molecular genetic characteristics of a family which coinheritance of rare-88 C>G (HBB:c.-138 C>G) β-thalassemia mutation with α-thalassemia and review of the literature

The molecular genetic characteristics of a family with rare -88 C>G (HBB: c.-138 C>G) β-thalassemia gene mutation were studied using cohort study. The cohort study was conducted from June to August 2022 by Prenatal Diagnosis Center of Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center. The phenotype and genotype were analyzed by hematological cytoanalyzer, automatic electrophoretic analysis system, and next-generation sequencing (NGS). And then, Sanger sequencing was used to verify the rare gene results. The results showed that the proband, her father, her uncle and her younger male cousin had discrete microcytosis (MCV 70.1 fl, 71.9 fl, 73.1 fl and 76.6 fl, respectively) and hypochromia (MCH 21.5 pg,22.0 pg,22.6 pg and 23.5 pg, respectively), elevated hemoglobin A2 level (5.3%, 5.4%, 5.4% and 5.5%, respectively), slightly elevated or normal fetal hemoglobin (Hb F), but no anemia. The proband was identified to have co-inherited ɑ-thalassemia (Hb Westmead gene heterozygous mutation, ɑwsɑ/ɑɑ) and β-thalassemia with a rare -88 C>G (HBB: c.-138 C>G) heterozygous mutation (β-88 C>G/βN). Her mother had the same α-thalassemia as the proband. Her father, her uncle and her younger male cousin had the same rare -88 C>G heterozygous mutations as the proband. While her grandmother and younger brother were not carrier of thalassemia. In conclusion, 4 cases of rare -88 C>G(HBB:c.-138 C>G) heterozygous mutation had been detected in a Chinese family. Carriers of this beta-thalassemia are clinically asymptomatic. This study enriches the knowledge of the thalassemia mutation spectrum in Chinese people and provides valuable information for genetic counseling, prenatal diagnosis, and prevention of thalassemia, providing a scientific basis for improving the quality of birth population and preventing birth defects.

Effect of megaloblastic anemia on hemoglobin A2 and diagnosis of β-thalassemia trait

β-thalassemia trait is usually diagnosed by raised hemoglobin A2 (HbA2). The presence of megaloblastic anemia can cause an increase in HbA2 and create a diagnostic dilemma. Here, we have analyzed the effect of vitamin B12 and folic acid supplementation on HbA2 and diagnosis of β-thalassemia trait in cases of megaloblastic anemia with raised HbA2. Cases of megaloblastic anemia with raised HbA2 on high-performance liquid chromatography (HPLC) were supplemented with vitamin B12 and folic acid. Post-treatment evaluation was done after 2 months. Cases showing adequate hematological response were subjected to statistical analysis. Based on post-treatment HbA2 value, the cases were diagnosed as normal, borderline raised HbA2, or β-thalassemia trait. Pre- and post-treatment values of red cell parameters and HbA2 were analyzed. There was a significant decrease in HbA2 value after vitamin B12 and folic acid supplementation. The diagnosis was changed in 70.97% of the cases after treatment. The chance of inconclusive diagnosis was decreased from more than 50% to less than 10%. Pre-treatment mean corpuscular volume (MCV) and HbA2% showed a significant difference between the thalassemic and normal groups. Megaloblastic anemia can lead to false-positive diagnosis of β-thalassemia trait on HPLC. Repeat HPLC should be done after adequate supplementation of vitamin B12 and folic acid in cases of megaloblastic anemia with raised HbA2. Red cell parameters are not helpful to suspect β-thalassemia trait in presence of megaloblastic anemia. However, HbA2% on HPLC can be a useful parameter to suspect or exclude β-thalassemia trait in cases of megaloblastic anemia.

Splenic infarction as a first clinical manifestation of sickle cell/beta+ thalassemia: a case report

Background: An association between splenic infarction, high altitude, and different subtypes of sickle cell disease (SCD) has been reported in the literature, particularly sickle cell trait. However, none of these studies reported the possibility of splenic infarction as a presenting feature of sickle cell/beta+ thalassemia. Case Presentation: A 23-year-old male college student presented to the emergency department with dull pain in the left upper quadrant and without any known history of medical illness. The patient was originally from Qatif, the Eastern Province of Saudi Arabia, and was referred to the study hospital with an ultrasound report showing splenic infarction. Upon presentation to the study hospital, the patient still had mild abdominal pain and early satiety. Examination revealed tachycardia (128/minute), upper abdominal tenderness, and splenomegaly approximately 2-3 cm below the left costal margin, with thrombocytosis and high lactate dehydrogenase (LDH) levels. Hemoglobin (HGB) electrophoresis showed hemoglobin A (HbA) 19.3; HbA2 4.9; hemoglobin F 12.9 and hemoglobin S 62.9, confirming a diagnosis of sickle cell/beta+ thalassemia. The patient was started on IV hydration and therapeutic anticoagulation with enoxaparin 60 mg subcutaneously every 12 hours. The patient&amp;apos;s symptoms improved. Therefore, the patient was discharged on life-long apixaban (5 mg PO Bid), with close follow-up at the hematology clinic. Conclusion: Splenic infarction could be manifested as an isolated feature in patients with SCD and its subtypes, such as sickle cell beta+ thalassemia. Therefore, physicians should pay careful attention to these complications and consider HGB electrophoresis as a part of the workup.

Diabetes with poor-control HbA1c is cardiovascular disease ‘risk equivalent’ for mortality: UK Biobank and Hong Kong population-based cohort study

IntroductionType 2 diabetes mellitus (T2DM) has traditionally been considered a coronary heart disease ‘risk equivalent’ for future mortality, but significant heterogeneity exists across people with T2DM. This study aims to...

High-performance liquid chromatography local reference ranges of hemoglobin fractions (HbA, HbA2, and HbF) in detection of hemoglobinopathies in western Kenya

High-performance liquid chromatography local reference ranges of hemoglobin fractions (HbA, HbA2, and HbF) in detection of hemoglobinopathies in western Kenya

Work-up of Patients with Decreased Hemoglobin A2 Identified by Capillary Zone Electrophoresis: A North American Institutional Experience.

Isolated low hemoglobin A2 (HbA2) is rarely encountered in our clinical practice using capillary zone electrophoresis. The study goal was to characterize the work-up at our institution of patients with low HbA2. Patients with low HbA2 and a control cohort with normal capillary zone electrophoresis were identified and relevant information extracted from the medical record. Of 44 patients with isolated decreased HbA2, 28 (64%) had corresponding complete blood count/ferritin values. Compared to control patients, patients with low HbA2 were more likely to have iron deficiency and demonstrated a more microcytic, hypochromic blood picture. However, 46% (13/28) of patients with low HbA2 and ferritin for evaluation did not have iron deficiency. Only 2 patients had genetic testing. This study redemonstrates the association between low HbA2 and iron deficiency and reinforces the need for iron indices to interpret capillary zone electrophoresis results. Our study population showed incomplete or absent iron studies in most cases.

Association of SLC22A1, SLC22A2, SLC47A1, and SLC47A2 Polymorphisms with Metformin Efficacy in Type 2 Diabetic Patients.

Response to metformin, first-line therapy for type 2 diabetes mellitus (T2DM), exists interindividual variation. Considering that transporters belonging to the solute carrier (SLC) superfamily are determinants of metformin pharmacokinetics, we evaluated the effects of promoter variants in organic cation transporter 1 (OCT1) (SLC22A1 rs628031), OCT2 (SLC22A2 rs316019), multidrug and toxin extrusion protein 1 (MATE1) (SLC47A1 rs2289669), and MATE2 (SLC47A2 rs12943590) on the variation in metformin response. The glucose-lowering effects and improvement of insulin resistance of metformin were assessed in newly diagnosed, treatment-naive type 2 diabetic patients of Han nationality in Chaoshan China (n = 93) receiving metformin. Fasting plasma glucose (FPG), fasting insulin (FINS), glycated hemoglobin A1 (HbA1C), homeostasis model assessment-insulin sensitivity (HOMA-IS), and homeostasis model assessment-insulin resistance (HOMA-IR) were the main metformin efficacy measurements. There were significant correlations between both SLC47A1 rs2289669 and SLC47A2 rs12943590 and the efficacy of metformin in individuals with T2DM. In normal weight T2DM patients, significant associations between the AA and GG genotypes of the rs2289669 variant of SLC47A1 and a greater reduction in FINS and HOMA-IR were detected. A significant correlation was observed between the AG genotype of the rs12943590 polymorphism of SLC47A2 and a greater reduction in HOMA-IR. Gene–environment interaction analysis showed that in the FINS interaction model, the second-order of dose30_g-SLC47A2 rs12943590 was statistically significant. The variants of SLC47A1 rs2289669 and SLC47A2 rs12943590 could be predictors of insulin resistance in type 2 diabetic patients treated with metformin. The second-order interaction of dose30_g-SLC47A2 rs12943590 may have a significant effect on FINS in patients with T2DM on metformin treatment. These findings suggest that promoter variants of SLC47A1 and SLC47A2 are important determinants of metformin transport and response in type 2 diabetes mellitus.

Prediabetes relates to impaired mitochondrial function in human ventricular myocardium

Abstract Background/Introduction With the growing prevalence of prediabetes in developed countries, complications of this predecessor of diabetes mellitus type 2 become increasingly important for medical research and practice. Prediabetes is defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and may also incorporate elevated hemoglobin A1. While overt type 2 diabetes is a well-established risk factor and can even be the cause of cardiac failure, this is not yet proven for prediabetes. Mitochondrial impairment is a key pathomechanism in heart failure, but it remains uncertain, whether prediabetes impairs myocardial energy metabolism in humans just as type 2 diabetes does. Purpose We aimed to scrutinize the impact of prediabetes on myocardial mitochondrial metabolism and cardiac function. Methods We included 50 heart transplant recipients with normal glucose tolerance (GT, n=25), prediabetes (n=8, 3 IFG and 5 IGT) or type 2 diabetes mellitus (T2DM, n=17), who had received a healthy donor heart from a non-diabetic donor. In this cohort, the impact of the recipients' metabolism should be displayed in the donor heart after transplantation. We performed oral glucose tolerance tests to assess the diabetes status, and cardiac magnetic resonance imaging to assess cardiac systolic and diastolic function, circulating biomarkers of oxidative stress in serum samples (thiobarbituric acid reactive substances (TBARS) and redox potential), as well as global T2 relaxation times as a marker of myocardial inflammation. In transcatheter endomyocardial biopsies, we assessed myocardial mitochondrial oxidative capacity using high-resolution respirometry and myocardial mRNA expression of nuclear factor kappa B p105 subunit (NFKB1). Results GT and IFG/IGT patients exhibited comparable demographic and clinical characteristics, whereas T2DM had higher BMI, glycemia, triglycerides and creatine kinase (all p&amp;lt;0.05). None of systolic (p=0.99), diastolic cardiac function (p=0.81), myocardial NFKB1 expression (p=0.74), circulating oxidative stress markers (p=0.94 and 0.95) or cardiac T2 relaxation times (p=0.99) were altered in IFG/IGT compared to GT, but diastolic strainrate was impaired (p=0.03) and circulating oxidative stress (TBARS: p=0.03, redox potential: p=0.04) were higher in T2DM than in GT. However, myocardial mitochondrial function stood out to be already impaired in IFG/IGT to a similar extend as in T2DM. This particularly applied to substrates of mitochondrial complex I (GT vs. IFG/IGT vs. T2DM: 126±7 vs. 89±12 vs. 93±6 pmol s–1 mg–1. p=0.02) and II (188±13 vs. 123±17 vs. 138±11 pmol s–1 mg–1. p=0.02). Intrinsic uncoupling was not altered in IFG/IGT but tended to be higher in T2DM (leak control ratio: 0.49±0.02 vs. 0.46±0.06 vs. 0.57±0.04 [arbirary units]). Conclusion Our findings point towards mitochondrial impairment as a predecessor of overt heart failure in prediabetes and may represent an early footprint of prediabetic cardiomyopathy. Funding Acknowledgement Type of funding sources: None.

Association of Lipopolysaccharide-Toll-Like Receptor 4 Signaling and Microalbuminuria in Patients with Type 2 Diabetes Mellitus.

PurposeIntestinal flora imbalance has been implicated in the activation of innate immunity in the kidneys. However, little is known about the potential links between lipopolysaccharide (LPS)-toll-like. receptor 4 (TLR4) signaling activated by intestinal barrier dysfunction and microalbuminuria in type 2 diabetes mellitus (T2DM).Patients and Methods61 patients with T2DM were stratified based on the absence (n=32) or presence (n=29) of microalbuminuria. There were also 28 control subjects. Urinary albumin excretion rate (UAER), serum levels of LPS, D-lactic acid (DLA), diamine oxidase (DAO), fasting blood glucose (FBG), interleukin-6 (IL-6), glycosylated hemoglobin A1 (HbA1c), and high-sensitivity C-reactive protein (hs-CRP), and TLR4 expression in peripheral blood mononuclear cells (PBMCs) were measured.Resultshs-CRP, IL-6, LPS, DLA, DAO, and TLR4 were markedly increased in subjects with T2DM compared to the controls (P < 0.05 for all). Moreover, LPS was positively correlated with FBG, HbA1c, hs-CRP, IL-6, UAER, DLA, DAO, and TLR4 (P < 0.05 for all). In addition, TLR4 was positively correlated with UAER, hs-CRP, FBG, DLA, HbA1c, and LPS (P < 0.05 for all). In regression analyses, TLR4, LPS, HbA1c, and hs-CRP were independently associated with UAER (P < 0.05 for all), while FBG, LPS, TLR4, and hs-CRP (P < 0.05 for all) were found to be risk factors for microalbuminuria in T2DM.ConclusionIntestinal integrity is compromised in subjects with T2DM, and the activation of LPS-TLR4 signaling might play an important role in the development of microalbuminuria in T2DM.

The Misdiagnosis of Beta-Thalassemia Heterozygosity Led by Hyperthyroidism

When patients have mild microcytic hypochromic anemia with slightly increased hemoglobin (Hb) A2 fraction, the most likely diagnosis is beta-thalassemia heterozygosity. But herein we found a patient who had all these hematological parameters but did not have beta-thalassemia heterozygosity. He was a 14-year-old Thai who presented with fatigue and heat intolerance for 2 weeks. His physical examination revealed mild diffuse enlargement of thyroid gland. Blood tests showed Hb 120 g/L, mean corpuscular volume (MCV) 72.1 fL, mean corpuscular hemoglobin (MCH) 23.3 pg/cell, free triiodothyronine (FT3) &gt; 20 pg/mL, free thyroxine (FT4) &gt; 5.0 ng/dL, thyrotropin &lt; 2.5 mIU/L, serum ferritin 51.3 µg/L, Hb A2 3.8%. Besides primary hyperthyroidism, he was diagnosed with beta-thalassemia heterozygosity. After being treated with antithyroid drug for 6 months, his blood tests showed subclinical hyperthyroidism, Hb 146 g/L, MCV 83.3 fL, MCH 26.3 pg/cell, Hb A2 3.0%. Not only the thyroid hormones levels but also the Hb concentration, MCV, and the Hb A2 percentage became normal. Due to this inconsistency, the DNA analysis for beta-thalassemia genes was performed and found negative for numerous common and rare beta-thalassemia genes meanwhile beta-globin gene sequencing appeared normal. It should be concluded that hyperthyroidism could induce slightly elevated Hb A2 percentage and mild hypochromic microcytic anemia in a normal individual, leading to the misdiagnosis of beta-thalassemia heterozygosity. In other words, Hb analysis should not be performed during hyperthyroidism and it should be delayed till achievement of the euthyroid stage.

Determination of hemoglobin-derived advanced glycation end products deploying metal salts in solution: Towards development of low-cost detection technique

The elevated blood sugar in Type II diabetes results in protein glycation that leads to the formation of Advanced Glycation Endproducts (AGEs) and cause severe pathogenic complications such as cardiovascular diseases, nephropathies, retinopathies, neurodegenerative diseases, etc. In our earlier work we have shown that gold nanoparticles (AuNPs) can be synthesized both in presence and absence of external reducing agent by in vitro generated AGEs from Hemoglobin A0 (HbA0). In the current work we have found that these highly reactive Hb derived AGEs (Hb-AGEs) are also capable of reducing silver ions and synthesize silver nanoparticles (AgNPs) with a different plasmonic response than the control solutions. It was observed that the concentration of AGE and metal salts play a vital role in the formation of nanoparticles and time-dependent stabilization of the particles. The lowest detection limit (LOD) showed that the reactions are highly sensitive because as low as 1 ng/μl of AGEs can be detected. When reduction of the two metal ions (Au 3 + and Ag + ) were compared it was found that the AuNPs could be a better choice for the colorimetric sensing due to the appearance of plasmon in the visible range, while AgNPs could serve as a cost-effective determinant of AGEs. Therefore, in conclusion we confirm that AGEs can be detected just by deploying metal salts in solution.

Reference intervals for erythrocyte parameters and hemoglobin electrophoresis parameters for young children in Guangxi.

Erythrocyte parameter analysis is the important means for diagnosis and treatment of hematological diseases, which are essential for screening of thalassemia in southern China combined with hemoglobin electrophoresis analysis. But little is known regarding the reference intervals (RIs) in healthy pediatrics in these two areas. 95% RIs of erythrocyte parameters were calculated from 853 healthy preschoolers, aged from 1 days to <6 years, according to the C28-A3C guidelines of the Institute of Clinical and Laboratory Standards. To express the magnitude of sex and age variation, standard deviation ratio (SDR) was calculated using ANOVA. Concurrently, we selected 3814 thalassemia carriers as carriers group and drew receiver operating characteristic (ROC) curves to establish the optimal cut-off values of hemoglobin electrophoresis parameters, which were used as the upper/lower limits of RIs to efficiently screen thalassemia. All parameters except red blood cell (RBC) required age partitioning, confirmed by SDRage above .4. There was no need for sex partitioning on all parameters, confirmed by SDRsex below .4. The optimal cut-off value of Hemoglobin A2 (Hb A2) in the four subgroups was <7.8% (Hb A), 2.3%-3.2%, 2.5%-3.6% and 2.6%-3.6%, respectively. In this study, the establishment of RIs improved the diagnostic efficiency of hematological disease (especially thalassaemia) for children in Guangxi. It provides reliable hematological references for the identification and diagnosis, treatment monitoring, and health screening of children's clinical diseases.

Transfusion support for patients with sickle cell disease

Red blood cell (RBC) transfusion is an essential treatment for many patients with sickle cell disease (SCD), whose RBCs express hemoglobin S (HbS), a mutated form of hemoglobin A (HbA). Transfusion goals include increasing blood oxygen carrying capacity and decreasing the relative amount of HbS to HbA to mitigate vaso-occlusion in small blood vessels. In situations where correction of severe anemia and reduction in HbS may be achieved without removal of RBCs, simple transfusion may be utilized. Partial manual RBC exchange, which removes blood containing HbS by phlebotomy and replaces with donor blood transfusion sequentially allows for larger changes in the ratio of HbS to HbA when compared to simple transfusion. Automated RBC exchange by apheresis is useful in situations where a rapid and drastic HbS reduction is indicated. Vascular access is an important consideration for transfusion. Although peripheral access may be sufficient, central venous catheters and implantable venous access devices may be necessary for adequate access over time. Blood bank considerations include adequate RBC antigen matching to mitigate the risk of RBC alloimmunization, of which patients with SCD are at risk of developing. Transfusion may be utilized in efforts to intervene in the evolution of potentially life-threatening complications of SCD such as acute stroke, severe acute anemia and acute chest syndrome. Transfusion is also useful in several non-acute settings, such as stroke prevention, pregnancy, pre-surgery, and transfusion support for curative therapies. Individualized treatment plans are an essential component of patient care. Continuous evaluation of clinical indications and evolution of guidelines will continue to optimize care for patients with SCD.