Hemoglobin最新文献

Thalassemia is one of the most common inherited blood disorders worldwide. This defect causes a disproportionate ratio of α- and β-globin chains resulting in ineffective erythropoiesis leading to increased iron absorption. In patients where the imbalance between α and β globin chains is great they are dependent on blood transfusions for survival. This results in transfusional iron overload but also comes with additional risks such as transfusion-transmissible viral infections like hepatitis B and C. This can lead to various complications like liver fibrosis, cirrhosis and hepatocellular carcinoma, which are important causes with morbidity and mortality in patients of thalassemia today. These hepatobiliary manifestations and their management are briefly discussed in this review. Understanding hepatobiliary complications in thalassemia is vital for optimizing patient care.

Ion-exchange high-performance liquid chromatography (HPLC) is commonly used to measure hemoglobin A1c (HbA1c) by distinguishing it from other hemoglobin (Hb) fractions based on net charge. Hb variants can interfere with this analysis, leading to spurious HbA1c results, particularly in HPLC-based methods. This study investigated blood samples showing an HV3 peak - which indicates an Hb variant - on the Tosoh G11 chromatogram during routine HbA1c analysis in a Danish laboratory. Over 30 workdays, 53/33,006 samples displayed an HV3 peak. Sanger sequencing identified Hb Riccarton as the most common variant associated with these peaks (n = 27), consistent with its prevalence in the Danish Blood Donor Study, suggesting it is common in the Danish Caucasian population. Hb Riccarton posed a particular analytical challenge, as over half of the cases showed fluctuating HV3 peaks, initially separated from the HbA1c fraction but subsequently integrated into it upon re-analysis. In regions where Hb Riccarton is prevalent, clinical laboratories using the Tosoh G11 must be aware of this phenomenon to avoid bias and inconsistency in HbA1c reporting. Following Hb Riccarton, HV3 peaks most often indicated HbE heterozygosity (n = 16). Compared to Tosoh G11, HbA1c from the DCA Vantage showed a mean bias of -9.7% for HbE, versus -2.1% in samples without Hb variants. For Hb Riccarton, the bias was -7.2% when the HV3-peak was integrated, and +8.6% when separated from the HbA1c fraction. However, if clinicians are aware of these variants being present, both methods may be used for diabetes monitoring if applied consistently.

Vaso-occlusive crisis (VOC) pain episodes often occur with menses and concurrent hormonal contraceptive use may reduce their frequency. This study tested the hypothesis that among women with sickle cell disease (SCD), sex hormones are associated with pain detection thresholds. Women with SCD aged minimum 18 years with regular menses, and without acute illnesses, pregnancy, oophorectomy, or hormonal contraceptive use within three months prior were included. Pain detection thresholds for heat (HPT) and pressure (PPT), and serum estradiol, progesterone and testosterone were measured at follicular and luteal phases. The Adult Sickle Cell Quality-of-Life Measurement Information System assessed quality-of-life and VOC frequency and severity scores. Generalized linear mixed models were performed, including the day of the cycle standardized by cycle length. Among 125 participants, neither the day nor phase of the menstrual cycle was associated with PPT or HPT. In multivariate analyses, worse VOC scores (β = 1.7) and severe genotype (β = -46.0) were associated with higher and lower trapezius PPT, respectively. Older age was associated with lower forearm HPT (β = -0.1). Among leg measurements, ovulatory cycles (β = -1.1) and hydroxyurea use (β = -1.2) were associated with lower HPT, while worse VOC scores (β = 0.1) were associated with higher HPT. Higher estradiol was associated with lower HPT at the leg (β = -0.02), with an interaction with the cycle day (β = 0.001) predicting lower thresholds earlier in the cycle for the same estradiol level. Estradiol is associated with a time-varying, length-dependent small-fiber neuropathy among SCD women; and may be a potential therapeutic target and biomarker for SCD pain.

We characterized here for the first time the deletional HbH disease caused by a large novel α⁰-thalassemia deletion in a 26-year-old Burmese pregnant woman. Capillary electrophoresis (CE) electropherogram revealed HbA₂ABart's H, whereas, a single-tube multiplex real-time PCR with EvaGreen and high-resolution melting (HRM) analysis for diagnosis of three common α⁰-thalassemia --^SEA, --^THAI, and --^CR deletions showed a negative result. Thus, a multiplex ligation-dependent probe amplification (MLPA) analysis was performed. The α-globin gene cluster deletion was observed spanning from upstream of HBZ to downstream of HBQ1 exon 3 covering three functional genes (HBZ, HBA2, and HBA1). This large novel deletion has not been reported previously thus we named it α⁰-thalassemia (--^BURMESE) due to its origin. In addition, deletional HbH disease is a result of compound heterozygosity for --^BURMESE/-α^3.7. Therefore, the characterization and identification of --^BURMESE is essential for genetic counseling and preventing new cases of HbH disease and Hb Bart's hydrops fetalis.

Type II methemoglobinemia is a rare genetic condition in which deficiency of the enzyme NADH-cytochrome b5 reductase 3 encoded by the gene CYB5R3 causes neurological symptoms in addition to elevated blood methemoglobin levels. The clinical presentation of Type II methemoglobinemia extends beyond hematological symptoms and include developmental delays, intellectual disability, and severe neurological symptoms. Here we present a case of a young male of Turkish origin diagnosed with type II hereditary methemoglobinemia at age 28. The proband has congenital hearing loss and was diagnosed with infantile autism in adolescence. After several hospital admissions with dyspnea, low oxygen saturation, methemoglobin levels at 4-19%, and normal p50 of 27.0 mmHg, he was evaluated for congenital methemoglobinemia. Genetic testing using targeted next generation sequencing identified the rare pathogenic CYB5R3 c.235C > T p.(Arg79Trp) missense variant (NM_001171660.2, NP_001165131.1). Enzymatic testing of NADH-cytochrome b5 reductase 3 of the patient and the mother showed decreased activities of 0.6 U/g Hb and 6.7 U/g Hb, respectively, compared to a normal group with a mean of 12 U/g Hb (standard deviation 1.7 U/g Hb). The patient had hemoglobin levels within normal and osmotic gradient ektacytometry was performed and found normal. To our knowledge, this constitutes the first report of a CYB5R3 c.235C > T homozygous. This case report emphasizes the importance of considering rare genetic disorders in patients with unexplained neurological and auditory deficits. The patient consented to publication of this case story.

A method based on transverse proton magnetic relaxation to determine the η_Hb is presented. The procedure is supported by the inverse relationship between η_Hb and T₂. The Hb samples were obtained starting from whole blood of healthy individuals and patients, which was processed by classical methods (centrifugation, decanting and freezing-thawing cycles). An Ostwald's viscometer was used to measure (293 K) η_Hb in Hb solutions of different concentrations and in non-diluted Hb samples belonging to healthy individuals. The CPMG pulse sequence was employed to determine T₂ in a Tecmag Magnetic Resonance console coupled to a magnet of 0.095 T, and the temperature of measurement was 293 K. A calibration curve of R₂ = 1/T₂ as a function of η_Hb was obtained, making possible the evaluation of this viscosity starting from the experimental measurement of T₂. A theoretical expression was derived, which properly describes the behavior of R₂ as a function of η_Hb and supports the obtained calibration curve. The method developed, using the transverse proton magnetic relaxation, was successfully used to calculate η_Hb in samples belonging to 10 healthy individuals, and its potential utility for medical applications was observed estimating η_Hb in samples belonging to 46 sickle cell disease patients. To use this method a special care must be taken with the temperature, the value of τ and the homogeneity of the static magnetic system. Additionally, the presence inside the sample of an external amount of water, paramagnetic compounds, and/or other biological materials must be avoided.

This prospective cross-sectional study was conducted at the Department of Hematology at Armed Forces Institute of Pathology Rawalpindi, Pakistan, from July 2023 to February 2025 after approval from Ethical Review Committee of the institute. Individuals being investigated for hemoglobinopathies in whom Hemoglobin D was detected, were included in the study. After detailed history and examination, investigations were performed including Complete Blood Counts (on Sysmex XN-3000), Capillary Zone Electrophoresis (on Sebia Capillarys 2 Flex-Piercing), High Performance Liquid Chromatography (on Bio-Rad D10) for differentiating Hb D-Punjab and D-Iran. Molecular studies (using PCR) were performed on samples in which a co-existing β thalassemia mutation was suspected on hemoglobin electrophoresis. Data collected was analyzed on Jamovi v2.4. Over 18 months, 2,171 individuals were tested for hemoglobinopathies, and Hb D, after excluding concomitant iron deficiency anemia, was detected in 106. Among these, 76 were found to have Hb D trait, 3 with homozygous Hb D disease, and 27 with compound heterozygous conditions. The compound heterozygous group included 21 patients of Hb D/β-thalassemia, 4 patients of Hb S/D, and 2 patients of Hb D/E. Hb D-Punjab accounted for 71% of the Hb D patients, and Hb D-Iran for the remaining 29%. Linear regression analysis revealed that MCH and RBC count showed significant positive correlations with Hb D levels. Molecular analysis identified specific β-thalassemia mutations in the Hb D/β-thalassemia cases, with IVS1-5 and FR 8-9 being the most common.

We present the case of a 71-year-old Spanish patient with a low Hb A₂ value by high-performance liquid chromatography (HPLC) and an atypical profile by capillary electrophoresis (CE), suggesting an Hb A₂ structural variant. Molecular biology revealed a non-described mutation in codon 132 of the 3rd exon of the HBD gene. This mutant allele codes for a change of amino acid (lysine to threonine) in position 10 of the helix H of the delta (δ) globin chain, described as HBD: c.398A > C or Hb A₂-Getafe. Detection of new variants in the δ-globin chain is crucial since these mutations may mask different pathologies, such as beta (β) thalassemia.

HbD-Punjab is prevalent in the north-western region of India with an estimated frequency of 2% in Punjab. The association of HbD-Punjab with HbS results in moderate-severe symptoms which are similar to the HbSS homozygous phenotype. Simultaneous presence of variant HbD with HbS favors polymerization of HbS molecules which results in serious consequences like sickle vaso-occlusion leading to diminished flow of blood through the capillaries supplying the bones resulting in ischemia, avascular necrosis, infarcts of bone, untimely closure of epiphyseal plates and stunted growth. This study describes a brief incident where a 28-year-old female, who presented with left sided hip pain, diagnosed with left hip femoral head Avascular Necrosis (AVN) (Grade-3). She was diagnosed with sickle cell anemia in a regional hospital at the age of six years and had undergone multiple blood transfusions. She had a history of right total hip replacement, left knee synovectomy and pain in multiple joints, including both the knees, elbows and shoulders. In view of severe anemia, hemoglobin fractionation was done using HPLC method which was suggestive of double heterozygous Hb SD-Punjab, genetic and family studies were recommended and there was no significant family history. This study enlightens the occurrence of adverse consequences in the presence of a double heterozygous Hb variant with one of the variants being Hb S. Laboratory investigations for identification and characterization of such variant hemoglobin is important for preventive and palliative care.

The introduction of iron chelation therapies has notably extended the life expectancy of individuals with β-thalassemia, thereby presenting the potential for the emergence of new complications such as renal impairments. Because creatinine levels are influenced by body mass and nutritional status, there is a need for a more sensitive and reliable indicator of renal glomerular function. Here, we studied 27 individuals with β-thalassemia undergoing iron chelation therapy with Deferasirox. The serum levels of cystatin-C, a highly sensitive biomarker for renal dysfunction, were quantified using an immunoturbidimetry assay. We subsequently analyzed the data, examining correlations with other clinical and laboratory parameters. We determined the glomerular filtration rate (GFR) using both creatinine and cystatin-C-based equations. According to the creatinine equation, none of the patients had a reduced GFR, but 59% exhibited a reduced GFR value based on the cystatin-C equation. Patients with elevated cystatin-C levels exhibited higher serum creatinine (p < 0.001) and BUN (p = 0.002) and lower ferritin (p = 0.023) levels. Our study revealed a positive correlation between cystatin-C and creatinine (p = 0.002), BUN (p = 0.018), and BMI (p = 0.046), while a negative correlation was observed with ferritin (p = 0.006). We found no correlation between cystatin-C and age, weight, height, Deferasirox therapy duration, or blood transfusion frequency. Multiple regression analysis indicated that ferritin (p = 0.003) significantly affected cystatin-C levels, while other variables did not. Additionally, no independent variables had a significant impact on creatinine levels. Since there is a high likelihood of subclinical renal impairment in these patients, we recommend regular monitoring of serum cystatin-C as a screening tool.