Mean Corpuscular Hemoglobin Levels Research Articles

Clinical and genetic characteristics of Chinese pediatric and adult patients with hereditary spherocytosis

ObjectiveThis study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype–phenotype correlations in Chinese patients with hereditary spherocytosis (HS).MethodsRetrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children's Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People's Hospital and The Third People's Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (< 14 and ≥ 14 years).ResultsA total of 34 HS patients were included in this study, comprising 22 children (64.70%) and 12 adults (35.30%). The probands who underwent genetic testing were derived from 34 unrelated families. Thirty-two variants were tested and 9 of them are novel. Eighteen cases had ANK1 variants, 15 had SPTB variants, and 1 had SLC4A1 variant. 25 patients performed core family members underwent genetic testing, 17 (68.0%, 17/25) were de novo, 5 (20.0%, 5/25) were maternally inherited, and 3 (12.0%, 3/25) were paternally inherited. ANK1-HS patients exhibited more severe anemia compared to cases with SPTB-HS, showing lower levels of RBC and HB (P < 0.05). Anemia was more severe in patients diagnosed in childhood than in those diagnosed in adulthood. Within the ANK1-HS group, MCH levels in adult patients was significantly higher than those in children (P < 0.05), while there were no significant differences in RBC, HB, MCV, and MCHC levels between two groups. Adult patients with SPTB-HS had significantly higher levels of RBC, HB, and MCH than pediatric patients (P < 0.05), while MCV and MCHC levels showed no significant statistical differences.ConclusionThis study conducted a comparative analysis of phenotypic characteristics and molecular genetics in adult and pediatric patients diagnosed with HS, confirming that pediatric ANK1-HS patients exhibit a more severe anemic phenotype compared to SPTB-HS patients, while the severity of HS in adults does not significantly differ between different causative genes.

Molecular characterization of similar Hb Lepore Boston-Washington in four Chinese families using third generation sequencing.

Hemoglobin (Hb) Lepore is a rare deletional δβ-thalassemia caused by the fusion between delta-beta genes, and cannot be identified by traditional thaltassemia gene testing technology. The aim of this study was to conduct molecular diagnosis and clinical analysis of Hb Lepore in four unrelated Chinese families using third generation sequencing. Decreased levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and an abnormal Hb band were observed in the probands of the four families. However, no common α and β-thalassemia variants were detected in the enrolled families using polymerase chain reaction-reverse dot blot hybridization based traditional thalassemia gene testing. Further third-generation sequencing revealed similar Hb Lepore-Boston-Washington variants in all the patients, which were resulted from partial coverage of the HBB and HBD globin genes, leading to the formation of a delta-beta fusion gene. Specific gap-PCR and Sanger sequencing confirmed that all the patients carried a similar Hb Lepore-Boston-Washington heterozygote. In addition, decreased levels of MCH and Hb A2 were observed in the proband's wife of family 2, an extremely rare variant of Hb Nanchang (GGT > AGT) (HBA2:c.46G > A) was identified by third-generation sequencing and further confirmed by Sanger sequencing. This present study was the first to report the similar Hb Lepore-Boston-Washington in Chinese population. By combining the utilization of Hb capillary electrophoresis and third-generation sequencing, the screening and diagnosis of Hb Lepore can be effectively enhanced.

Effects of smokeless nicotine on blood physiology, biochemical, and histological alterations using Labeo rohita as a model organism.

The present research was conducted to evaluate the negative effects of nicotine powder on the blood physiology, and biochemical and histological alterations of Labeo rohita. Fish were divided into four groups (1-4). Fish groups 2, 3, and 4 were exposed to different concentrations of nicotine, such as 0.75, 1.25, and 1.75 mg/l, while group 1 acted as a control. To find out the long-term impact of nicotine on body physiology, we conducted a 42-day experiment. After the completion of the experiment, hematology, biochemical assays, and histology were done. Results revealed a considerable increase in HGB, red blood cells, WBCs, hematocrit, mean corpuscular volume, red cell distribution width -SD, procalcitonin, neutrophils, lymphocytes, monocytes, triglycerides, total cholesterol, low-density lipoprotein, very low-density lipoprotein, alanine transaminase, aspartate aminotransferase, globulin, thyroid stimulating hormone, BUN, creatinine, and blood glucose levels, whereas mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, RDW, platelet, high-density lipoprotein, albumin, total proteins, and T3 levels were significantly (p ≤ 0.05) decreased in exposed fish as compared to control group fish. Histological alterations showed that exposure to smokeless nicotine causes deleterious and degenerative effects in the liver, kidney, and gills of exposed fish. Nicotine administration in fish results in adverse effects on different biochemical and hematological parameters and causes histological alterations in some vital organs of exposed fish.

Third-generation sequencing identified two rare α-chain variants leading to hemoglobin variants in Chinese population.

Rare and novel variants of HBA1/2 and HBB genes resulting in thalassemia and hemoglobin (Hb) variants have been increasingly identified. Our goal was to identify two rare Hb variants in Chinese population using third-generation sequencing (TGS) technology. Enrolled in this study were two Chinese families from Fujian Province. Hematological screening was conducted using routine blood analysis and Hb capillary electrophoresis analysis. Routine thalassemia gene testing was carried out to detect the common mutations of α- and β-thalassemia in Chinese population. Rare or novel α- and β-globin gene variants were further investigated by TGS. The proband of family 1 was a female aged 32, with decreased levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), Hb A2, and abnormal Hb bands in zone 5 and zone 12. No common thalassemia mutations were detected by routine thalassemia analysis, while a rare α-globin gene variant Hb Jilin [α139(HC1)Lys>Gln (AAA>CAA); HBA2:c.418A>C] was identified by TGS. Subsequent pedigree analysis showed that the proband's son also harbored the Hb Jilin variant with slightly low levels of MCH, Hb A2, and abnormal Hb bands. The proband of family 2 was a male at 41 years of age, exhibiting normal MCV and MCH, but a low level of Hb A2 and an abnormal Hb band in zone 12 without any common α- and β-thalassemia mutations. The subsequent TGS detection demonstrated a rare Hb Beijing [α16(A14)Lys>Asn (AAG>AAT); HBA2:c.51G>T] variant in HBA2 gene. In this study, for the first time, we present two rare Hb variants of Hb Jilin and Hb Beijing in Fujian Province, Southeast China, using TGS technology.

Ker-050 Treatment Reduced Iron Overload and Increased Bone Specific Alkaline Phosphatase in Participants with Lower-Risk MDS Supporting Potential to Restore Balance to the Osteohematopoietic Niche

Background: Iron overload (IO) in myelodysplastic syndromes (MDS) contributes to the deterioration of the osteohematopoietic niche (OHN), where hematopoietic and osteogenic precursors interact to regulate hematopoiesis and bone metabolism. Excess iron exacerbates ineffective hematopoiesis, inflammation, and bone loss via direct effects on resident hematopoietic and osteogenic precursors. Iron chelation therapy (ICT) is associated with improved event-free survival in patients with MDS but does not address the underlying cause of IO and introduces patient burden due to tolerability and cost. KER-050 is an investigational, modified activin receptor type IIA ligand trap designed to inhibit select TGF-β superfamily ligands (activins A, B, GDFs 8, 11) and promote differentiation and maturation of erythroid and megakaryocytic precursors. KER-050 has potential to reduce dependence on red blood cell transfusions and increase iron utilization via erythropoiesis, possibly mitigating IO at its source. As previously reported from an ongoing Phase 2 study (NCT04419649), KER-050 treatment in participants with lower-risk (LR) MDS resulted in rates of modified IWG 2006 Hematological Improvement-Erythroid (HI-E) and transfusion independence (TI) of 51.4% and 42.3%, respectively, with a mean decrease in ferritin (322 ng/mL at Week 24) among HI-E and/or TI responders. KER-050 treatment also demonstrated effects on osteogenic precursors, including prevention of bone loss in a mouse model of MDS and dose-dependent increases in bone specific alkaline phosphatase (BSAP), a marker of bone formation, observed in healthy postmenopausal women. Thus, KER-050 has potential to address the multifaceted pathogenesis of MDS, including IO. Here, we present new data from the ongoing Phase 2 study in MDS, exploring the potential of KER-050 to provide benefit beyond hematologic responses and to ameliorate IO in MDS. Methods: This ongoing Phase 2 study is evaluating KER-050 in participants with LR MDS. Data from exploratory assessments of markers of IO, hematopoiesis, and bone turnover are presented as of a cutoff date of April 3, 2023, for all participants who had received the recommended Part 2 dose (RP2D; 3.75-5 mg/kg q4wks). Results: Baseline ferritin levels in RP2D participants (N=59) were generally elevated, while levels of mean corpuscular hemoglobin and reticulocyte hemoglobin were in the normal range (Table 1). After KER-050 treatment, sustained decreases in serum ferritin were observed among participants with baseline levels ≥1000 ng/mL (Figure 1), likely driven in part by reduced transfusion burden in responders. Concomitant increases observed in soluble transferrin receptor (sTfR; Figure 1) suggest that increased erythropoiesis may also have contributed. Mean decreases in ferritin observed in non-transfused (NT) participants (-228 ng/mL at Week 24, n=7) indicate potential for KER-050 to affect iron homeostasis by mechanisms other than transfusion reduction. In 1 NT participant receiving ICT, the baseline ferritin of 1632 ng/mL decreased to &amp;lt;500 ng/mL over 32 weeks, leading to ICT discontinuation and coinciding with an increase in hemoglobin (Hgb) from 9.2 g/dL at baseline to 11.3 g/dL over the same period. In another NT participant not receiving ICT, ferritin decreased from 1094 ng/mL at baseline to 884 ng/mL and 583 ng/mL at Weeks 24 and 68, respectively, while Hgb gradually increased from 9.94 g/dL at baseline to 10.7 and 12.2 g/dL at Weeks 24 and 68. KER-050 treatment was also associated with increases in BSAP, a new finding in this MDS population that is consistent with prior observations in preclinical and healthy volunteer studies. Despite some heterogeneity, mean increases of 8.47% (n=23) and 10.4% (n=13) were observed at Weeks 24 and 48, respectively; 3 participants with erythroid responses had increases in BSAP of ≥30% at these time points. Summary: Exploratory data indicate potential for KER-050 to drive meaningful decreases in ferritin in participants with LR MDS, particularly among those with IO. While transfusion reduction likely contributes, observations in NT participants highlight the potential for enhancement of erythropoiesis to improve IO, irrespective of transfusions. Observed changes in BSAP suggest that KER-050 is also acting on osteogenic precursors, with the potential to provide functional improvements within the OHN. Updated results will be provided at the presentation.

Prevalence and genetic analysis of triplicated α-globin gene in Ganzhou region using high-throughput sequencing.

α-globin gene triplication carriers were not anemic in general, while some studies found that α-globin gene triplication coinherited with heterozygous β-thalassemia may cause adverse clinical symptoms, which yet lacks sufficient evidence in large populations. In this study, we investigated the prevalence and distribution of α-globin gene triplication as well as the phenotypic characteristics of α-globin gene triplication coinherited with heterozygous β-thalassemia in Ganzhou city, southern China. During 2021-2022, a total of 73,967 random individuals who received routine health examinations before marriage were genotyped for globin gene mutations by high-throughput sequencing. Among them, 1,443 were α-globin gene triplication carriers, with a carrier rate of 1.95%. The most prevalent mutation was αααanti3.7/αα (43.10%), followed by αααanti4.2/αα (38.12%). 42 individuals had coinherited α-globin gene triplication and heterozygous β-thalassemia. However, they did not differ from the individuals with heterozygous β-thalassemia and normal α-globin (αα/αα) in terms of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels. In addition, heterogenous clinical phenotypes were found in two individuals with the same genotype. Our study established a database of Ganzhou α-globin gene triplication and provided practical advice for the clinical diagnosis of α-globin gene triplication.

Effect of Morinda citrifolia fruit powder on physiological and productive performance of Cavia porcellus.

The breeding of guinea pig is part of the pluriactivity for millions of farming families in rural areas from the Peruvian Andean and Amazonian regions and other South American Andean countries. Rearing these specie plays an important source of employment, income, and nutrition for millions of rural families on these countries. The search of natural products for enhancing animal wellbeing, health, and production and thereby of guinea pigs is being searched nowadays. The aim of this study was to determine the effect of the ripe fruit powder of Morinda citrifolia on the physiological and productive performance parameters of reared guinea pigs under humid tropical conditions and to find a new use of noni fruit and to improve the guinea pig as an agrifood product. For this purpose, forty-eight male Peru breed guinea pigs sixty days old, were used and distributed into four treatments with diets containing 0, 2, 4 and 8% of the noni ripe fruit powder, with four replicates and 3 guinea pigs each. Erythrocytes, hematocrit, hemoglobin profiles, hematological indices MCV (mean cell volume), MCHC (mean corpuscular hemoglobin concentration), MCH (mean corpuscular hemoglobin) and blood metabolites profiles: TP (total protein), ALB (albumin), GLO (globulin), TC (total cholesterol) were determined. The productive performance indices: DWG (daily weight gain), DCFI (daily concentrated feed intake), TFIFM (total feed intake of fresh matter) and TFIDM (total feed intake of dry matter), FRCFM (feed rate conversion for fresh mater) and FRCDM (feed rate conversion for dry matter) were evaluated. The guinea pigs were evaluated at 60, 75 and 90 days old. The interaction between noni fruit powder and the age of guinea pigs produced an increase in the erythrocyte, hematocrit, MCH and MCHC levels at 75 days old, (p < 0.05). The final weight and the daily weight gain increased, while the feed rate conversion for fresh and dry matter decreased, as the level of noni fruit powder in the diet increased until 4% (p < 0.05). Thus, the level of noni ripe fruit powder in the guinea pigs' diets had a positive effect on the erythrocyte, leucocytes, hematocrit, MCH, MCHC levels, the final weight, the daily weight gain, and the feed rate conversion of fresh and dry matter.

HAEMATOLOGICAL ALTERATIONS IN CALVES WITH ACUTE RESPIRATORY DISTRESS SYNDROME DUE TO ASPIRATION PNEUMONIA: A PROSPECTIVE STUDY

The aim of this prospective study was to investigate the arterial blood gas (ABG) analysis, which is considered the gold standard, and complete blood count (CBC) as a complementary test in neonatal calves with acute respiratory distress syndrome (ARDS) due to aspiration pneumonia. Ten healthy and 20 calves with ARDS due to aspiration of milk/colostrum were enrolled in the study. Clinical examinations were performed at admission. ABG analyses were performed to determine the presence of ARDS and investigate the extent of lung ventilation/damage. CBC analysis was performed from venous blood samples. Heart and respiratory rates and body temperature values were higher in diseased calves than healthy ones (p &lt; 0.000). Arterial pH, partial pressure of oxygen in arterial blood (PaO2) and saturation of oxygen in arterial blood (SaO2) were lower (p &lt; 0.001) in the diseased calves, while partial pressure of carbon dioxide in arterial blood (PaCO2) and lactate levels were higher (p &lt; 0.000) than those in healthy ones. Also, leukocyte (WBC), lymphocyte, monocyte, granulocyte, mean corpuscular volume (MCV), and mean corpuscular haemoglobin (MCH) levels were higher in the diseased calves than the healthy calves (p &lt; 0.032). As a result of the correlation analysis, the only correlation was determined to be between PaO2 and WBC, which was moderately negative. As a result, it was observed that leukocytosis developing in respiratory diseases that cause severe inflammatory processes such as aspiration pneumonia was negatively correlated with PaO2 and could potentially exacerbate hypoxia, and ABG evaluation with CBC could provide useful clinical data in calves with ARDS due to aspiration pneumonia.

Effects of spirulina Spirulina platensis meal as a feed additive on growth performance and immunological response of Gangetic mystus Mystus cavasius

The aim of this study was to investigate the effects of dietary Spirulina platensis supplementation on the growth and immunity of Mystus cavasius. Fish were fed on the experimental diets, where the fish meal was replaced with S. platensis meal at 0%, 2.5%, 5.0%, 7.5%, and 10% levels, respectively. Triplicate groups of fish were fed with each diet twice a day near satiation and reared for 10 weeks. After the trial, serum lysozyme levels, whole-body composition, feed utilization, growth performance, and blood characteristics were examined. The pathogenic Aeromonas hydrophila was administered intra-peritoneally to 10 fish from each group and monitored for daily mortality rate. Metagenomics analysis was used to investigate the gut microbiota. When more than 7.5% of fish meal in the diet was replaced with S. platensis meal, the body weight, and specific growth rate were higher than in the control diet. The protein efficiency and feed conversion ratio were also positively affected by dietary S. platensis meal supplementation. The replacement of 7.5–10% fishmeal with S. platensis increased the whole-body protein and ash contents more than the control. The red blood cells, white blood cells, hemoglobin, hematocrit, and mean corpuscular hemoglobin levels of M. cavasius rose when fish were fed 7.5–10% S. platensis compared with the control. The serum lysozyme test result showed an increase in the lysozyme value as dietary S. platensis supplementation was gradually increased. The abundance of bacterial composition was found to be higher with gradually increasing S. platensis supplementation, especially up to 5–10% supplementation level. The total mortality of fish was decreased with higher inclusion of S. platensis when challenged by A. hydrophila. These findings suggest that dietary S. platensis has positive effects on the growth and immune system of M. cavasius, and maintaining dietary replacement of 7.5–10% fish meal with S. platensis can be suggested for feed formulation of M. cavasius.

Evaluation of qSOFA and variation of hematochemical profile in cats naturally infected with feline panleukopenia virus

Abstract Feline panleukopenia (FP) is a fatal viral disease that predisposes cats to sepsis and organ failure. Owing to a wide variety of clinical findings, hematochemical examinations are significant for the determination of early signs of disease-related complications. The aim of this study is to investigate the diagnostic efficacy of certain hematochemical parameters together with quick Sepsis-related Organ Failure Assessment (qSOFA) in cats with FP. A total of 10 healthy and 30 panleukopenic cats were included in this study. Physical examinations revealed that the body temperature was highest in septic panleukopenic cats (p &lt; 0.009) and they had higher qSOFA scores (p = 0.000). Hemogram analysis revealed that leukocyte, lymphocyte, granulocyte, erythrocyte, and hemoglobin levels were lower in non-septic panleukopenic cats compared with the healthy ones (p &lt; 0.030). Also, monocyte and mean corpuscular hemoglobin levels were lower in septic ones (p &lt; 0.048). Serum biochemistry profiling revealed higher blood urea nitrogen, creatinine, alanine aminotransferase, lactate dehydrogenase, total bilirubin, and C-reactive protein levels in panleukopenic cats (p &lt; 0.033). As a result, it was concluded that although the qSOFA is not sufficient to distinguish sepsis in cats, unlike dogs, in order to achieve a positive clinical outcome, when evaluated together with hematochemical variables, it may help in making early diagnosis of FP-related complications.

Assessment of maternal and cord blood hematological alterations in mothers with gestational diabetes mellitus: A comparative study with healthy pregnant women and their newborns

Background: Gestational diabetes mellitus (GDM) is a prevalent condition with potential repercussions on glucose metabolism and possibly on various hematological parameters. Exploring these alterations provides insights into the systemic manifestations and implications for maternal and neonatal health. Aims and Objectives: The primary aim of this study was to assess the hematological variations observed in maternal and cord blood between GDM mothers and non-GDM counterparts. Furthermore, based on these hematological markers, we sought to evaluate the potential ramifications of GDM on maternal and neonatal health. Another goal was to contrast the hematological features in newborns born to GDM mothers with those born to non-GDM mothers. Materials and Methods: A case–control study was conducted at MES Medical College, Central Research Department in Perinthalmanna, Kerala. Pregnant women from the Malappuram district admitted to the labor ward and met the inclusion criteria were involved. The study enrolled 100 GDM pregnant women as cases and 50 healthy pregnant women as controls. Hematological analysis was performed on maternal venous blood samples and cord blood samples, evaluated at the Central Laboratory of MES Medical College. Statistical analysis was performed using IBM SPSS version 20. Results: Significant hematological variations were observed between the two groups. Maternal blood of GDM patients showed a higher red blood cell (RBC) count and differences in mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) compared to controls. Cord blood samples from GDM neonates reflected elevated RBC, MCV, and MCH levels, with a pronounced white blood cells count higher than non-GDM neonates. Several parameters, including hemoglobin, MCH concentration, and platelet counts, remained consistent across groups. Conclusion: ???.

Additional value of red blood cell parameters in predicting uncommon α-thalassemia; experience from 10 years of α-globin gene sequencing and copy number variation analysis.

The diagnosis of rare forms of α-thalassemia requires laborious genetic analyses. Accurate sample selection for such evaluation is therefore essential. The main objectives of this study were to investigate the predictive power of red blood cell parameters to detect rare forms of α-thalassemia (substudy 1), and to explore the frequency of rare versus common forms of α-thalassemia in our sample population (substudy 2). In substudy 1, we reviewed all blood samples selected for extended α-hemoglobinopathy evaluation at our laboratory during 2011-2020 (n= 1217), which included DNA sequencing and/or copy number variation analysis. We assessed α-thalassemia positive samples at different levels of mean corpuscular hemoglobin (MCH) alone and in combination with results for red blood cell count (RBC) or red cell distribution width (RDW). In substudy 2, we examined the distribution of α-thalassemia genotypes for all samples submitted to a first-tier hemoglobinopathy evaluation at our laboratory during 2014-2020 (n= 6495). In substudy 1, both RBC and RDW added predictive value in detecting rare forms of α-thalassemia in samples from adults and children. In adult samples with MCH ≤ 23 pg, the presence of erythrocytosis increased the detection rate from 27% to 74% as compared to non-erythrocytosis, while normal RDW increased the detection rate from 36% to 86% as compared to elevated RDW. In substudy 2, rare forms of α-thalassemia were detected in 12% of α-thalassemia positive samples. Initial assessment of MCH, RBC, and RDW provided valuable predictive information about the presence of rare forms of α-thalassemia during hemoglobinopathy evaluation.

Impact of age-dependent red blood cell parameters on α-globin gene genotyping in children.

When screening for α-thalassemia in children, adult cut-offs for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) are generally applied to guide genetic evaluation. However, the normal ranges for MCV and MCH are lower in children than in adults, so we hypothesized that using age-matched cut-offs could lead to a more rational diagnostic strategy. The aim of this study was to evaluate if age-matched cut-offs could be applied advantageously. Data on children referred to a hemoglobin fractionation at the Department of Clinical Biochemistry, Aarhus University Hospital between 2016-2021 were identified in the laboratory information system. α-globin gene (HBA1/HBA2) genotyping was performed using multiplex gap-polymerase chain reaction. A total of 387 children were identified. HBA1/HBA2-genotyping was performed in 207 children (53%), and α-thalassemia was diagnosed in 47 children (23%) with -α3.7/αα being the predominant genotype (13%). We found that 23 children had MCV and MCH levels in the normal age-matched range, and two of these children (9%) were α+ thalassemia carriers with three functional α-globin genes. Using age-specific cut-off levels resulted in a reduction of 23 (11%) genotypes performed. In conclusion, applying age-matched cut-offs for MCV and MCH when screening children for α-thalassemia lead to 11% fewer genotypes performed while 9% carriers of α+ thalassemia (of the medically innocuous genotype -α3.7/αα) would have been overlooked.

Safety assessment of the Quercus brantii gall hydroalcoholic extract: Single and repeated oral dose toxicity studies.

Quercus brantii galls (QBGs) are well-known in Iranian traditional medicine for treating various diseases. The aim of study was to assess the acute and repeated oral toxicity of the hydroalcoholic extract of QBG in female rats. The ethanolic extract of QBG was administered in rats by gavage in both acute and repeated dose models. In the acute section of the study, a single oral dose of 2000 mg/kg was administered to female rat which were observed for physical symptoms and behavioral changes for 14 days. In the repeated dose toxicity study, the QBG extract (50, 500, and 1000 mg/kg/day) was administered for a period of 28 days to rats. On 28th day of experiment, blood sampling of animals was done for hematological and biochemical analysis and then sacrificed for histopathological examination of the harvested tissues (liver, heart, kidney, lung, spleen, stomach, ovary and uterus). A single oral administration of the QBG extract (2000 mg/kg) did not produce mortality or significant behavioral changes during 14 days of observation. In repeated oral toxicity models, the extract significantly increased (P<0.05) the levels of mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), thyroid-stimulating hormone (TSH) and significantly decreased the levels of triiodothyronine (T3) and thyroxin (T4) in 500 and 1000 mg/kg dosage. The histopathological studies showed the absence of toxic effects of QBG (50 mg/kg dosage) and revealed evidence of microscopic lesions in the liver, kidney, stomach, heart, spleen, lung, uterus, and ovary in the 500- and 1000-mg/kg groups. The results indicate that the oral acute toxicity of QBG extract was of a low order with LD50 being more than 2000 mg/kg in rats. In addition, slight tissue damage was observed in some tissues in the 500 and 1000 mg/kg groups. It was found that prolonged use at higher doses i.e. 500 mg/kg/day of QBG extract should be avoided.

Identification of variants in 94 Chinese patients with hereditary spherocytosis by next-generation sequencing.

Hereditary spherocytosis (HS) is the most common type of hereditary erythrocyte membrane disease and has varied phenotypic features and genetic patterns. We herein performed a retrospective study of 94 patients with HS and aimed to investigate the genetic variations and genotype-phenotype correlations using targeted next-generation sequencing. In 79/94 (84%) patients, 83 HS variants including 67 novel variants were identified. Pathogenic variants of SPTB, ANK1, SLC4A1, SPTA1, and EPB42 were found in 32/79(41%), 22/79(28%), 15/79 (19%), 8/79 (9%), and 3/79 (4%) of the patients respectively, revealing that SPTB is the most frequently mutated HS gene in Eastern China. Most SPTB and ANK1 gene variations were nonsense and frameshift variations. Missense variants were the main variant type of SLC4A1, SPTA1, and EPB42 genes. Interestingly, one SPTA1 variant (p. Arg1757Cys) showed an autosomal dominant inheritance pattern and one EPB42 variant (p. Gln377His) was apparent as a hotspot variation. Furthermore, genotype-phenotype analysis was performed among the five mutated gene groups. Besides the finding that patients with the SLC4A1 variant had the highest mean corpuscular hemoglobin levels, no clear correlations between genotype and phenotype were observed.

Association between Oxidative Stress Parameters and Hematological Indices in Breast Cancer Patients.

Background Breast cancer is one of the leading causes of death in women worldwide. This causes an increase in free radicals, resulting in oxidative stress. The aim of this study was to determine the effect of breast cancer on oxidative stress and its relationship with hematological indices. Methods This case-control study included 43 women with breast cancer and 37 age-matched healthy controls. Oxidative stress and its correlation with hematological profiles over seven months were evaluated. Finally, the data were compared between the two groups using the t-test and Pearson's test, and the results were analyzed using the SPSS 24 software. Results The results revealed that patients with breast cancer had significantly increased hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) levels compared with healthy subjects (p < 0.05). In addition, oxidative stress parameters, such as superoxide dismutase (SOD), catalase (CAT), total oxidant status (TOS), and total antioxidant capacity (TAC), were significantly elevated. Glutathione peroxidase (GPX) and malondialdehyde (MDA) were significantly lower in patients with breast cancer than in the control group (p < 0.05). Statistical significance in hematological indices showed a positive or negative correlation with oxidative stress parameters. Conclusion Women with breast cancer showed a deranged complete blood count (CBC) pattern compared to healthy individuals.

Evaluation of pharmacological efficacy and safety of hydroxyurea in sickle cell disease: Study of a pediatric cohort from Chhattisgarh, India

Sickle cell disease (SCD) is a disease of abnormal hemoglobin associated with severe clinical phenotype and recurrent complications. Hydroxyurea (HU) is one of the US-FDA approved and commonly used drug for the treatment of adult SCD patients with clinical ­severity. However, its use in the pediatric groups remains atypical. Despite a high prevalence of the disease in the state Chhattisgarh, there is a lack of evidence supporting its use in pediatric patients. This study aimed to evaluate the pharmacological and clinical efficacy and safety of HU in a large pediatric cohort with SCD from Central India. The study cohort consisted of 164 SCD (138 Hb SS and 26 Hb S beta-thalassemia) children (≤14 years of age) on HU therapy, who were monitored for toxicity, hematological and clinical efficacy at baseline (Pre-HU) and after 24 months (Post-HU). The results highlight the beneficial effects of HU at a mean dose of 18.7 ± 7.0 mg/kg/day. A significant improvement was observed, not only in physical and clinical parameters but also in hematological parameters which include fetal hemoglobin (Hb F), total hemoglobin, hematocrit, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels, when evaluated against the baseline. We did not observe any significant adverse effects during the treatment period. Similar results were obtained on independent analysis of Hb SS and Hb Sβ patients. These findings strengthen the beneficial effect of hydroxyurea in pediatric population also without any serious adverse effects and builds up ground for expanding its use under regular monitoring.

Mean corpuscular hemoglobin predicts the length of hospital stay independent of severity classification in patients with acute pancreatitis.

Mean corpuscular hemoglobin (MCH) is a common blood routine test index. To explore the relationship between MCH and length of hospital stay in patients with acute pancreatitis (AP), we included 273 patients with AP without coronary heart disease, diabetes, hypertension and anemia in this study. All data were separated into three groups according to the length of hospital stay. Gender (p = 0.017) and severity classification (p < 0.001) were significantly correlated with length of hospital stay among three groups. Notably, MCH level was significant different among three groups (p = 0.009). Thus, all data were separated into two groups according to MCH level, and significant increases in the length of hospital stay were observed between two groups (p = 0.030). A positive correlation between length of hospital stay and MCH was observed (r = 0.172, p = 0.004). Multiple linear regression analysis showed that MCH was independent correlated with the length of hospital stay, no matter whether severity classification of AP was included (beta = 0.248, p < 0.001; beta = 0.212, p < 0.001). Our results demonstrated that the length of hospital stay was correlated with MCH level in patients with AP, and MCH level at admission may predict the length of hospital stay independent of severity classification in AP. These results may provide a potential evaluation basis for the management of patients with AP.

Genome-Wide Association Study on the Hematological Phenotypic Characteristics of the Han Population from Northwest China.

BackgroundHematological characteristics have positive reference value as clinical indicators in the evaluation of various diseases. The purpose of this study was to determine the gene loci associated with 20 hematological phenotypes in the Han population from northwest China.MethodsA genome-wide association study (GWAS) was conducted on hematological indicators of 1005 Han people from northwest China. Genotyping was performed with a GeneTitan multichannel instrument and Axiom Analysis Suite 6.0. Using the 1000 Genomes Project (phase 3) as a reference, haplotype imputation was performed with IMPUTE2. SNVs (single nucleotide variants) significantly associated with hematological phenotypes were identified. The top SNV (p < 5E-7) was then selected for replication detection.ResultsNinety genetic variations identified in the GWAS were significantly associated with hematological indicators. Among them, only rs35289401 (CCDC157) was significantly associated (genome-wide) with red blood cell distribution width (RDW) (p = 4.21E-08). The fourteen top SNVs were selected for replication verification and were significantly associated with hematological phenotypes. However, only HBS1 L-MYB rs1331309 was significantly associated with the mean hemoglobin content (p = 6.42E-07). We also found that the mean corpuscular hemoglobin (MCH) level in the rs1331309 GG/GT genotype was significantly higher than that in the TT genotype (p = 0.023).ConclusionThe GWAS identified a total of 90 genetic variants significantly associated with hematological phenotypic indicators. In particular, rs1331309 (HBS1 L-MYB) is expected to be a biomarker for monitoring the dynamics of MCH levels. This study provides a reference for related studies on the genetic structure of hematological characteristics. It provides a valuable reference for the clinical diagnosis or prediction of a variety of diseases.

P1557: DISTINGUISHING OF IRON REFRACTORY IRON DEFICIENCY ANEMIA FROM IRON DEFICIENCY ANEMIA AND THALASSEMIA TRAIT BY SYSMEX RESEARCH RED CELL PARAMETERS

Background: Iron refractory iron deficiency anemia (IRIDA), iron deficiency anemia (IDA), and Thalassemia trait (TT) are the most common causes of microcytic anemia. It is possible to discriminate between IDA and TT by routine complete blood count (CBC), hemoglobin (Hb) electrophoresis and iron parameters; however, it is very difficult to distinguish IRIDA from IDA and TT using only routine CBC and iron parameters. Aims: The aim was to distinguish IRIDA from IDA and TT using Sysmex research red cell parameters. Methods: The study included a total of 25 patients (n=10, TT; n=10, true IDA; n= 5, genetically confirmed IRIDA). Traditional [mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell count (RBC), and red cell distribution volume (%RDW)] and new red cell parameters [percentage hypochromic RBCs (%Hypo-He); percentage microcytic RBCs (%Micro-R)] were measured in a Sysmex-XN®2000 (Sysmex Corporation, Kobe, Japan), along with iron parameters. Participants’ disorders were categorized based on patients’ ferritin, Hb electrophoresis, genetic results, and CBC values. Results: Compared with the IDA patients, IRIDA patients had significantly higher mean levels of ferritin, RBC, %Hypo-He, %Micro-R and significantly lower mean levels of serum iron level MCV, MCH, and MCHC values (p<0.05 for all). Compared with TT patients, IRIDA patients had significantly higher mean levels of ferritin, %Hypo-He and %RD,W and significantly lower mean levels of serum iron level and MCH values (p<0.05 for all). The RBC, Micro-R, Hypo-He, MCV and MCH cut-off values for discriminating IRIDA from IDA patients were 4.9µL, %60, 50%, 60fL, and 16.0pg, respectively. The RDW, Hypo-He, and MCH cut-off values for discriminating IRIDA from TT patients were %19, %30, and 17.0pg, respectively. Summary/Conclusion: This first study has examined the utility of new red cell parameters in patients with IRIDA. Our findings should be confirmed in larger studies; however, we believe that higher percentage of hypochromic microcytic erythrocytes with an elevated RBC value may be useful predictors for distinguishing IRIDA from IDA patients. As well, a moderate percentage of hypochromic erythrocytes with high RDW value can guide physicians in discriminating IRIDA from TT patients