Hemoglobin最新文献

β-Thalassemia is a hereditary hemoglobinopathy characterized by chronic anemia, iron overload, and sustained oxidative stress, leading to progressive multisystem complications. Although oxidative stress is well documented in β-thalassemia, its association with peripheral biomarkers reflecting mitochondrial oxidative metabolism and neuroaxonal protein homeostasis has not been sufficiently investigated. This study aimed to evaluate serum monoamine oxidase (MAO) activity and total Tau protein levels in patients with β-thalassemia major and minor compared with healthy controls, with an emphasis on phenotype-dependent peripheral biochemical alterations related to disease severity. A total of 90 participants were enrolled, including 20 patients with β-thalassemia major, 30 with β-thalassemia minor, and 40 healthy controls. Serum MAO activity and total Tau protein concentrations were measured using ELISA-based assays. Intergroup comparisons were performed using one-way analysis of variance followed by Tukey's post hoc test. Serum MAO activity was significantly higher in the β-thalassemia major group compared with both β-thalassemia minor patients and controls (p < 0.001). Total Tau protein levels were significantly reduced in β-thalassemia major patients, whereas no significant difference was observed between β-thalassemia minor patients and healthy controls. Subgroup analyses revealed positive correlations within both β-thalassemia major and minor groups, consistent with a phenotype-dependent divergence and indicative of Simpson's paradox. In conclusion, β-thalassemia major is characterized by elevated serum MAO activity and reduced total Tau protein levels, reflecting concurrent alterations in systemic oxidative metabolism and peripheral Tau homeostasis. These findings represent peripheral biochemical signatures associated with disease severity rather than direct evidence of central nervous system pathology.

Fat embolism syndrome (FES) in sickle cell disease (SCD) remains a significant diagnostic and therapeutic challenge, often associated with high morbidity and mortality. While red blood cell exchange (RCE) is the standard first-line therapy, some cases continue to deteriorate despite aggressive management. Emerging evidence suggests that therapeutic plasma exchange (TPE) may serve as valuable salvage therapy, potentially improving survival in refractory cases. We present two cases of FES in SCD, both marked by an attack of profound hypotension and multiorgan dysfunction, yet with distinct trajectories and responses to therapy. The first case involved a 34-year-old female with FES refractory to conventional treatment, including RCE. A single session of TPE led to rapid clinical stabilization and recovery. The second case described a 28-year-old female with a more severe disease course, requiring five cycles of combined RCE and TPE before achieving clinical improvement and recovery. These cases underscore the potential role of TPE as an adjunct to RCE in managing FES in SCD and highlight the need for further research to establish its efficacy in this critical setting.

Hemoglobinopathies are common genetic disorders that can affect neonates. This study aimed to evaluate the prevalence of various hemoglobin variants in newborns and identify diagnostic cutoff levels for predicting homozygosity for HbS and HbD using capillary electrophoresis and molecular sequencing. A total of 2,609 newborns were screened at Lok Nayak Hospital (LNH) and Swami Dayanand Hospital (SDH) between January 2020 and October 2021. Newborns with HbA levels ≤15% or preterm deliveries were excluded. Capillary electrophoresis was performed on dried blood spot samples. Follow-up cascade screening was done for parents and siblings of positive cases, with molecular confirmation by gene sequencing. ROC curve analysis was used to determine predictive cutoff levels for homozygosity. Of 2,163 eligible neonates, 67 (3.1%) had structural hemoglobinopathies, with the most common being HbD (1.4%), followed by HbS (0.8%). Homozygous HbD, HbS, and HbE were observed. ROC curve analysis indicated that neonatal HbD levels ≥17.6% predicted homozygosity with 100% sensitivity and 96% specificity (area under the curve = 0.984), while HbS levels ≥57.4% predicted homozygosity with 100% sensitivity and 92% specificity (area under the curve = 0.917). These structural hemoglobinopathies were present in 3.1% of neonates, with HbD being the most prevalent variant. The relative levels of various types of neonatal hemoglobins can serve as reliable predictors for homozygosity, providing an effective method for early diagnosis of hemoglobinopathies in neonates.

Silent carrier or minor α-thalassemia (α-thal) is generally considered asymptomatic or associated with mild anemia in only a few cases. However, it is not uncommon for individuals with these conditions to seek outpatient care because of anemia. Which factors contribute to the development of anemia in this population? We retrospectively observed the individuals at a general hospital in central China, a non-endemic area for thalassemia. A total of 142 participants confirmed by thalassemia genetic testing were enrolled, including 54 cases of silent carrier and 88 cases of minor α-thal. Among the participants, 88 cases (62%) were diagnosed with anemia, as their hemoglobin (Hb) concentrations were below the lower limit of the reference range recommended by the World Health Organization (WHO) for their respective gender and age groups. Multivariate analysis of anemia revealed that the -^SEA/αα genotype (P = 0.014, OR = 2.503, 95%CI: 1.203-5.204) was an independent risk factor for anemia and deserves proactive anemia management. Iron deficiency (serum ferritin <30 ng/ml) has not been identified as a risk factor, but it is found to have a high incidence (18.2%) in the anemic group and requires further investigation with a larger sample size in this population.

Hemoglobin (Hb) Sogn is a rare Hb variant discovered in Norwegians and their descendants. Previous reports suggested no clinical symptoms in the heterozygote, but mild in vitro instability of the variant. Our recent clinical observations prompted suspicion of mild hematological abnormalities. This study aimed to evaluate hematological parameters and Hb fractions in individuals heterozygous for Hb Sogn, compared with those with Hb D-Punjab, to confirm or refute this suspicion. Data from 105 individuals with Hb Sogn and 145 with Hb D-Punjab were evaluated. Hematological parameters (Hb, RBC, MCH) and Hb fractions were compared using Mann-Whitney U tests. Different exclusion criteria were applied in the analysis for different parameters due to age- and sex-dependent reference intervals. In silico tools were used to predict pathogenicity. Individuals with Hb Sogn had lower MCH (median 28 pg vs 29 pg) and a lower variant fraction (median 33.6% vs 40.9%) compared with Hb D-Punjab. The HbA₂ fraction was higher in the Hb Sogn group (median 3.3% vs 2.9%). In silico prediction suggested a functional impact of Hb Sogn but did not reveal an effect on splicing. This study, involving the largest cohort of Hb Sogn carriers to date, suggests that heterozygous Hb Sogn exhibits a mild thalassemic phenotype. These findings may explain slightly reduced MCH values in affected individuals and could reduce the need for extended α-thalassemia investigation.

Comprehensive strategies are crucial for alleviating the substantial burden of sickle cell disease (SCD) in sub-Saharan Africa. Allogeneic hematopoietic stem cell transplantation (alloHSCT) offers a potentially scalable and cost-effective cure for eligible SCD patients; however, it is currently available in only seven African countries due to difficulties in implementing alloHSCT in Low- and Middle-Income Countries (LMICs). These challenges include limited and underdeveloped healthcare infrastructure, high rates of infectious diseases worsened by emerging multidrug-resistant pathogens, restricted access to effective antimicrobial agents, and the lack of advanced transplant technologies such as T-cell depletion, HLA typing laboratories, and stem cell processing facilities. The shortage of specialized supportive care and trained staff, along with inadequate access to chemotherapeutic and immunosuppressive drugs, further hampers progress. Additionally, there is no health insurance coverage for procedures like HSCT, forcing patients and their families to pay out of pocket, which makes HSCT unaffordable for many who could greatly benefit from it. Government support remains far below what is necessary to expand transplant capacity. For those who can afford it, medical tourism for HSCT outside Africa is increasing. Unfortunately, many of these patients return to environments with limited expertise and resources for post-transplant follow-up care. This article discusses the challenges faced in establishing a dedicated alloHSCT program for SCD at a tertiary hospital in Lagos, Nigeria, and explores opportunities for improvement.

A problem in hemoglobin studies is separating the allosteric and affinity factors that account for differences in the oxygen partial pressure at 50% saturation among various hemoglobins. Like oxygen binding to the hemes, the reaction of Ellman's reagent, 5,5'-dithiobis(2-nitrobenzoate)-DTNB for short-with the 93β sulfhydryl groups of hemoglobin is a reversible process. However, the reaction of DTNB with Cys93β of hemoglobin is devoid of allosteric factors. We present the results of equilibrium studies of the reaction of DTNB with thirty-eight heme-liganded hemoglobins between pH 5.6 and 9. Over a considerable pH range, inositol hexakisphosphate (inositol-P₆) decreases the DTNB affinities of hemoglobins that have the R2 quaternary structure. By contrast, inositol-P₆ increases the DTNB affinities of hemoglobins that have the R quaternary structure. Theoretical analyses of the pH dependence profiles show that inositol-P₆ lowers the DTNB affinities of R2-state hemoglobins by shifting the equilibrium between two tertiary structures, r and t, in favor of the r structure. By contrast, inositol-P₆ increases the DTNB affinities of R-state hemoglobins by shifting the r⇌t tertiary equilibrium in favor of the t structure. We suggest that the differences in the oxygen affinities of various hemoglobins may be accounted for, partially, by differences in their tertiary equilibria.

The HBD gene (MIM#142000) encodes the δ-globin chain, a β-like subunit of the HbA₂ fraction. In this study, we report two novel HBD variants identified in the Chinese population. Sanger sequencing revealed two types of novel mutations: [HBD:c.349C > A; CD 116 CGC > AGC (Arg > Ser)] and [HBD:c.201G > C; CD 66 AAG > AAC (Lys > Asn)]. Hemoglobin analysis by capillary electrophoresis indicated that the levels of HbA₂ were reduced to 1.2%, while the percentages of the corresponding HbA₂ variants were 0.5% and 0.7%. Neither of the two HBD mutations was associated with a decrease in mean corpuscular volume (MCV) or mean corpuscular hemoglobin (MCH). They have been named HbA₂-Shenzhen and HbA₂-Zhanjiang, respectively, according to their place of origin.

Accurate quantification of hepatic iron overload is essential for managing patients with thalassemia major to prevent severe complications such as liver and cardiac failure. Magnetic resonance imaging (MRI) T₂* has emerged as the noninvasive gold standard for assessing tissue iron concentration. This study aimed to localize and validate MRI T₂* measurement protocols and to evaluate the impact of region-of-interest (ROI) selection on iron overload classification in patients with thalassemia. A cohort of 39 patients with confirmed thalassemia from Imam Ali Hospital, Zahedan, underwent liver MRI with T₂* imaging. The effect of ROI variation on T₂* values and patient classification was analyzed. Validation was performed using healthy volunteers and iron phantoms with known concentrations. Statistical analyses compared results with those from hospital reports and from phantom and healthy subjects. ROI selection significantly affected T₂* values, resulting in reclassification in 35.9% of patients. Phantom studies demonstrated a strong linear correlation (R² ≈ 0.98) between T₂* values and iron concentration, confirming measurement accuracy. Healthy volunteers showed T₂* values within normal ranges, consistent with published data. Discrepancies between hospital reports and study findings highlighted the necessity for standardized imaging protocols and automated data processing to reduce variability. ROI selection critically affects hepatic T₂* measurements and the clinical classification of iron overload in patients with thalassemia. Standardized protocols, rigorous equipment calibration, and localized analytical tools are essential for enhancing diagnostic precision and patient management. This approach reduces dependence on external services and supports the provision of sustainable, high-quality care for patients with thalassemia.

We report a novel β-globin chain variant identified in a proband who is also a carrier of β-thalassemia. Glycated hemoglobin analysis revealed an elevated Hb A_1c level of 20.34% using high-performance liquid chromatography (HPLC), while the fasting blood glucose level was 5.49 mmol/L. Subsequent testing using an alternative HPLC system showed an Hb A_1c value of 2.8%, and the immunoturbidimetric assay failed to yield a detectable result. Sanger sequencing confirmed the presence of two heterozygous point mutations in the β-globin gene: CD1 (GTG > CTG) (HBB:c.4G > C) and CD17 (AAG > TAG) (HBB:c.52A > T). Hemoglobin analysis showed the variant electrophoresing at the HbA position. The HBB:c.4G > C mutation represents a previously unreported variant, which has been designated Hb Yongning based on the proband's geographical origin.