Correlation of Hemoglobin Level With New Inflammatory Markers in the Emergency Department: A Retrospective Study Exploring Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte, Platelet-to-Lymphocyte, and Mean Platelet Volume-to-Platelet Count Ratios.

Background Anemia of chronic disease is known to be associated with inflammation. However, the relationship between hemoglobin (Hb) levels and potential inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume-to-platelet count ratio (MPV/PC) has not been extensively studied. The primary objective of this retrospective analytical study conducted at Al Zahraa Hospital University Medical Center (ZHUMC), Beirut, was to investigate the correlation between Hb levels and potential inflammatory markers (NLR, MLR, PLR, MPV/PC) in patients visiting the emergency department (ED), across different genders and age groups. The secondary objectives were to compare Hb levels and inflammatory markers values between the referred medical ward group (the hospitalized patients who were admitted to the medical ward), and the non-referred to medical ward group (the patients who were discharged home from the ED), and to evaluate the predictability of inflammatory markers and Hb levels for referral to the medical ward, including the determination of optimal cutoff values for hospital admission to the medical ward. Methods We analyzed the blood parameters of 379 adult patients who presented to the ED with various medical complaints between September 1, 2022, and November 30, 2022 (three months). These patients were included in the study after we checked their eligibility regarding the verification of all our inclusion and exclusion criteria. Results Our findings revealed a significant negative correlation between Hb levels and PLR (r = -0.24) in both genders and across different age groups. The group referred to the medical ward exhibited lower Hb levels and higher NLR, MLR, and PLR values (P < 0.001). NLR/Hb ratio emerged as a predictive factor for admission in genitourinary (R² = 0.158; OR = 5.62) and respiratory groups (R² = 0.206; OR = 5.89), with specific cutoff values of 0.533 (Sensitivity = 57.1% & Specificity = 84.2%) and 0.276 (Sensitivity = 85% & Specificity = 51.1%), respectively. Conclusions Our study demonstrates that hemoglobin level negatively correlates with PLR. NLR, MLR, and PLR stand as important inflammatory markers. Moreover, we present the first study in the literature to show that NLR/Hb ratio can serve as a predictor for referral to the medical ward, particularly in the genitourinary and respiratory patient groups, underscoring its value in risk assessment as a prognostic marker reflecting the need for admission when the case is more serious.

A Comparative Study of Iron Status in Subclinical Hypothyroid and Euthyroid Subjects in a Tertiary Care Hospital.

BACKGROUND: The physiological equilibrium of the entire human body's metabolism is significantly influenced by thyroid hormones. Subclinical hypothyroidism, which is often concealed, is connected to iron deficiency anemia and various other hematological disorders. We in the current study tried to determine the prevalence and severity of iron deficiency anemia and investigate the correlation of subclinical hypothyroidism with iron deficiency. METHODS: A total of 100 subjects included in the study were divided into two groups. Group 1 included 50 cases with subclinical hypothyroidism, and Group 2 included 50 healthy age- and sex-matched controls. Hemoglobin (Hb) levels were measured within 24 hours of sample collection using a Sysmex automated cell counter (Kobe, Hyogo, Japan). Thyroid hormones (free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH)) were measured. RESULTS: Out of 50 cases, 48 (96%) have iron deficiency anemia, and 52 (104%) have subclinical hypothyroidism. Among the cases with iron deficiency anemia, 43 (86%) also have subclinical hypothyroidism. There was a negative correlation between thyrotropin (TSH) and Hb levels. Pearson's correlation coefficient "r" values were -0.86408. The serum ferritin levels of cases were decreased as compared to the healthy controls, and the difference in means for cases and controls in terms of serum ferritin is also statistically significant. CONCLUSION: The prevalence of anemia in subclinical hypothyroidism is significantly elevated, and considering the absence of significant clinical manifestations in the early stages, it is recommended to routinely conduct investigations for early detection, facilitating prompt management. Consequently, our study emphasizes that both overt and subclinical hypothyroidism should be recognized as risk factors for the development of iron deficiency anemia.

Early Onset of Severe Anemia Caused by Hb Calgary (HBB: C.194G > T): Another Case Report.

Unstable hemoglobin (Hb) variants are a rare cause of congenital hemolytic anemia. We describe a Chinese girl who presented with transfusion-dependent anemia in early infancy. Her diagnosis of Hb Calgary [ß64(E8)Gly > Val; HBB:c.194G > T] was not made until molecular testing was performed at the age of 5 years. Our case highlights the importance of early genetic testing in order to make the diagnosis, which may not only be useful for patient management and family counseling, but also for avoiding further unnecessary investigative attempts.

A 6-Year Follow-up of a Chinese Child with Homozygous ß0-Thalaasemia and a Heterozygous KLF1 Mutation.

Patients with the genotype of ß0/ß0 for ß-thalassemia (ß-thal) usually behave as ß-thal major (ß-TM) phenotype which is transfusion-dependent. The pathophysiology of ß-thal is the imbalance between α/ß-globin chains. The degree of α/ß-globin imbalance can be reduced by the more effective synthesis of γ-globin chains, and increased Hb F levels, modifying clinical severity of ß-TM. We report a Chinese child who had homozygous ß0-thal and a heterozygous KLF1 mutation. The patient had a moderate anemia since 6 months old, keeping a baseline Hb value of 8.0-9.0 g/dL. She had normal development except for a short stature (3rd percentile) until 6 years old, when splenomegaly and facial bone deformities occurred. Although genetic alteration of KLF1 expression in ß0/ß0 patients can result in some degree of disease alleviation, our case shows that it is insufficient to ameliorate satisfactorily the presentation. This point should be borne in mind for physicians who provide the genetic counseling and prenatal diagnosis to at-risk families.

A Review of the Occurrence of Intraventricular Hemorrhage in Preterm Newborns and its Future Neurodevelopmental Consequences.

Intraventricular hemorrhage (IVH) is a type of bleeding that occurs through the germinal matrix and comes through the ependymal cells into the ventricular cavity. It is mostly seen in preterm neonates but can also be seen sometimes in term neonates. Various factors predispose to preterm delivery; it can be spontaneous or medically induced. Spontaneous IVH occurs in cases of intrauterine infections in the mother, and it can be induced in cases of medical emergencies such as preeclampsia and eclampsia. The brain of a preterm newborn is not fully developed as it does not have pericytes and proteins, so it can bleed very quickly, which can cause IVH. Also, the vessels supplying the germinal matrix are immature and highly vascularized. IVH has four grades based on findings detected on cranial ultrasound and MRI. Management includes medical and surgical management; medical management includes phenobarbitone used for seizures and prophylaxis. Surgical management includes drainage, irrigation, and fibrinolytic therapy (DRIFT), and neuro-endoscopic lavage. IVH causes various short-term and long-term neurodevelopmental consequences. Long-term complications include cerebral palsy and intellectual disability, which hamper the life of the child. It mainly presents with seizures, flaccidity, decerebrate posture, etc. Various preventive measures can be taken to tackle IVH in newborns. First of all, preterm delivery should be avoided, and intrauterine infections in mothers should be treated. The administration of corticosteroids should be done for all preterm deliveries as it helps in the maturation of organs. The administration of magnesium sulfate should be done as it is neuroprotective and reduces cerebral palsy in the future. Delayed cord clamping is to be done to reduce recurrent blood transfusions and decrease the risk of IVH. This article explains the pathogenesis, management, prevention, and future outcomes of IVH.

Impact of Anemia on The Quality of Life of Chronic Kidney Disease Patients: A Single Institution Experience.

BACKGROUND: Anemia is a common complication of chronic kidney disease (CKD) and has been shown to worsen as CKD advances. CKD negatively impacts patients' health-related quality of life. It is therefore necessary to determine the impact of anemia on the quality of life in patients with CKD. OBJECTIVES: We assessed the relationship between the severity of anemia and its impact on the quality of life of anemic CKD patients attending nephrology clinics. METHODOLOGY: A cross-sectional study of one hundred and sixty-three subjects which included 102 CKD patients with anemia and sixty-one CKD subjects without anemia, was done between April 2016 and January 2017. Karnofsky's structured questionnaire was used for the quality of life, while the packed cell volume was used to determine the severity of anemia. RESULTS: The prevalence of anemia among CKD subjects was 102(62.6%), and it significantly worsens as CKD advances, which ranged from 42.3% in stage 3 to 93% in stage 5 (p < 0.001). The mean physical performance score was significantly lower among anemic CKD subjects than among controls, which was 73.17 ± 12.95 and 84.59 ± 11.04 respectively (P < 0.001). Furthermore, the mean physical performance score decreases significantly with the advancing CKD among both study groups. CONCLUSION: This study showed that CKD patients with anemia had significant impairment in their physical ability than CKD patients without anemia.

CONTEXTE: L'anémie est une complication fréquente de la maladie rénale chronique (MRC) et a tendance à s'aggraver à mesure que la MRC progresse.La MRC a un impact négatif sur la qualité de vie liée à la santé des patients. Il est donc nécessaire de déterminer l'impact de l'anémie sur la qualité de vie des patients atteints de MRC. OBJECTIFS: Nous avons évalué la relation entre la gravité de l'anémie et son impact sur la qualité de vie des patients atteints de MRC anémiques fréquentant les cliniques de néphrologie. MÉTHODOLOGIE: Une étude transversale portant sur cent soixante-trois sujets, dont 102 patients atteints de MRC avec anémie et soixante et un sujets atteints de MRC sans anémie, a été réalisée entre avril 2016 et janvier 2017. Le questionnaire structuré de Karnofsky a été utilisé pour évaluer la qualité de vie, tandis que le volume globulaire a été utilisé pour déterminer la gravité de l'anémie. RÉSULTATS: La prévalence de l'anémie chez les sujets atteints de MRC était de 102 (62,6 %), et elle s'aggrave significativement à mesure que la MRC progresse, passant de 42,3 % au stade 3 à 93 % au stade 5 (p < 0,001). Le score moyen de performance physique était significativement plus bas chez les sujets atteints de MRC anémiques que chez les témoins, soit 73,17 ± 12,95 et 84,59 ± 11,04 respectivement (p < 0,001). De plus, le score moyen de performance physique diminue significativement avec la progression de la MRC dans les deux groupes d'étude. CONCLUSION: Cette étude a montré que les patients atteints de MRC avec anémie présentaient une altération significative de leur capacité physique par rapport aux patients atteints de MRC sans anémie. Mots-clés: MRC,Anémie, Qualité de vie (QdV), Hémoglobine (Hb).

Concomitant Presence of Hb Agrinio and - -Med Deletion in a Greek Male Patient with Hemoglobinopathy H: More Severe Phenotype and Literature Review.

Hemoglobin (Hb) Agrinio is a rare non-deletional a-globin mutation observed almost exclusively in Greek, Spanish or other Mediterranean families. The clinical manifestations of a carrier of a single Hb Agrinio mutation (single heterozygosity) depend on the concomitant presence or absence of other mutations or variants in the beta, alpha or other modifying genes. We present a Greek patient harboring a Hb Agrinio variant plus the - -Med alpha deletional allele, having an infrequent severe form of alpha thalassemia, in contrast to the typical alpha thalassemic patient and requiring regular red blood cell (RBC) transfusions and chelation treatment. We also provide a concise literature review regarding alpha thalassemic hemoglobin variants and their molecular and clinical combinations. A phase 2, double-blind, randomized, placebo-controlled, multicenter clinical trial to determine the efficacy and safety of luspatercept (BMS-986346/ACE-536) for the treatment of anemia in adults with alpha thalassemia with the participation of our center is currently recruiting patients (NCT05664737).

Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice.

CONTEXT: Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms of IDR are unknown, limiting its application. OBJECTIVE: This study explores the therapeutic mechanisms of IDR in DSS-induced colitis using transcriptomic analysis. MATERIALS AND METHODS: Male BALB/c mice were categorized to six groups: normal, DSS model (2% DSS), IDR treatment (10, 20 and 40 mg/kg), and sulfasalazine (520 mg/kg) groups. The drugs were intragastrically administered for 7 consecutive days. The disease activity index (DAI) was recorded. After euthanasia, the colon length was measured, and histopathological examination, immunohistochemistry staining using F4/80, and colonic transcriptomic analysis were conducted. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) were conducted to verify our findings. RESULTS: Compared with DSS, IDR treatment decreased the DAI score by 64.9% and increased colon length by 26.2%. Moreover, it alleviated mucosal injury and reduced macrophage infiltration. Transcriptomic analysis identified several downregulated genes (Igkvs and Nlrp3), as well as Nlrp3/Il1ß and hemoglobin gene networks, after IDR treatment. The abundances of NF-κB p65, NLRP3, IL-1ß, and HBA decreased by 69.1, 59.4, 81.1, and 83.0% respectively, after IDR treatment. DISCUSSION AND CONCLUSION: Apart from the well-documented NF-κB signalling pathway, IL-17A, and NLRP3-IL-1ß, the suppression of haemoglobin-induced lipid peroxidation could be a previously unknown mechanism of IDR. Our study can help improve its application for UC treatment.

Determinants of hyperphosphatemia and its relation with hemoglobin levels among hemodialysis patients in two hospitals from Syria: a prospective cross-sectional study.

Hyperphosphatemia and anemia were both associated with several complications in chronic kidney disease (CKD) patients. This study aimed to determine the risk factors of hyperphosphatemia and its relation with anemia among hemodialysis (HD) patients. Secondly, it aimed to determine the prevalence of hyperphosphatemia and anemia. Material and methods: A prospective cross-sectional study was conducted among 146 HD patients from two HD centers in Syria, between June 2021 and March 2022. All patients at least 18 years old on maintenance HD were enrolled. The threshold of phosphorus (phos) level was divided by the upper normal range among HD patients (5.5 mg/dl). We used parametric and nonparametric statistics, the Pearson and Spearman correlations with simple and multiple linear regressions between study variables. Results: 36.9% of patients had a serum phos level of 5.5 or less (norm phos group), and 63.1% of patients had a serum phos level higher than 5.5 (high phos group). Also, 60.9% of patients had hemoglobin (Hb) less than 10 g/dl, and 40.4% of patients had Hb at least 10 g/dl. Age, type of HD access, phos binders (P-binders), parathyroid hormone (PTH), and calcium (Ca) showed significant effects on phos levels. Most patients were using arteriovenous fistula (AVF) (89.7%) as a HD access, and the meantime on HD was higher in the norm phos group compared to the high phos group. In a multivariate and univariate logistic regression analysis, hyperphosphatemia increased with increasing urea (Ur) and creatinine (Cr) levels, while the odds declined with increasing time on HD. Hb did not show a significant relation with phos by using several statistical methods. Discussion/Conclusion: A high prevalence of hyperphosphatemia and anemia was encountered among this sample of HD patients from Syria. There was no correlation between phos and Hb levels in contrast to previous conflicting studies, which mandates future studies to evaluate this correlation and further efforts to determine the range of phos that could have a benefit on anemia with respect to other comorbidities.

Fist Detection of Hb Suqian[ß42(CD1) Phe→Leu, HBB:c.129T > A] in Han Chinese.

We have identified a variant on the ß-globin gene in a Chinese female. Sequencing of the HBB gene revealed a Phe→Leu substitution at codon 42[ß42(CD1) Phe→Leu, HBB:c.129T > A] which has been named Hb Suqian for where the proband was born.

α- and ß-Globin Gene Mutations in Individuals with Hemoglobinopathies in the Chattogram and Sylhet Regions of Bangladesh.

Hemoglobinopathies, including α- and ß-thalassemias and sickle cell disease, are among the most widely disseminated hereditary blood disorders worldwide. Bangladesh is considered a hotspot for hemoglobinopathies, and these diseases cause a significant health concern in the country. However, the country has a dearth of knowledge on the molecular etiology and carrier frequency of thalassemias, primarily due to a lack of diagnostic facilities, limited access to information, and the absence of efficient screening programs. This study sought to investigate the spectrum of mutations underlying hemoglobinopathies in Bangladesh. We developed a set of polymerase chain reaction (PCR)-based techniques to detect mutations in α- and ß-globin genes. We recruited 63 index subjects with previously diagnosed thalassemia. Along with age- and sex-matched control subjects, we assessed several hematological and serum indices and genotyped them using our PCR-based methods. We identified that parental consanguinity was associated with the occurrence of these hemoglobinopathies. Our PCR-based genotyping assays identified 23 HBB genotypes, with the codons 41/42 (-TTCT) (HBB: c.126_129delCTTT) mutation leading the spectrum. We also observed the presence of cooccurring HBA conditions, of which the participants were not aware. All index participants in this study were on iron chelation therapies, yet we found they had very high serum ferritin (SF) levels, indicating inefficient management of the individuals undergoing such treatments. Overall, this study provides essential information on the hemoglobinopathy mutation spectrum in Bangladesh and highlights the need for nationwide screening programs and an integrated policy for diagnosing and managing individuals with hemoglobinopathies.

Isoelectric point barcode and similarity analysis with the earth mover's distance for identification of species origin of raw meat.

In this work, by combining the microcolumn isoelectric focusing (mIEF) and similarity analysis with the earth mover's distance (EMD) metric, we proposed the concept of isoelectric point (pI) barcode for the identification of species origin of raw meat. At first, we used the mIEF to analyze 14 meat species, including 8 species of livestock and 6 species of poultry, to generate 140 electropherograms of myoglobin/hemoglobin (Mb/Hb) markers. Secondly, we binarized the electropherograms and converted them into the pI barcodes that only showed the major Mb/Hb bands for the EMD analysis. Thirdly, we efficiently developed the barcode database of 14 meat species and successfully used the EMD method to identify 9 meat products thanks to the high throughput of mIEF and the simplified format of the barcode for similarity analysis. The developed method had the merits of facility, rapidity and low cost. The developed concept and method had evident potential to the facile identification of meat species.

A reliable and high throughput HPLC-HRMS method for the rapid screening of ß-thalassemia and hemoglobinopathy in dried blood spots.

OBJECTIVES: Traditional methods for ß-thalassemia screening usually rely on the structural integrity of hemoglobin (Hb), which can be affected by the hemolysis of red blood cells and Hb degradation. Here, we aim to develop a reliable and high throughput method for rapid detection of ß-thalassemia using dried blood spots (DBS). METHODS: Hb components were extracted from a disc (3.2 mm diameter) punched from the DBS samples and digested by trypsin to produce a series of Hb-specific peptides. An analytical system combining high-resolution mass spectrometry and high-performance liquid chromatography was used for biomarker selection. The selected marker peptides were used to calculate delta/beta (δ/ß) and beta-mutated/beta (ßM/ß) globin ratios for disease evaluation. RESULTS: Totally, 699 patients and 629 normal individuals, aged 3 days to 89 years, were recruited for method construction. Method assessment showed both the inter-assay and intra-assay relative standard deviation values were less than 10.8%, and the limits of quantitation for the proteo-specific peptides were quite low (1.0-5.0 µg/L). No appreciable matrix effects or carryover rates were observed. The extraction recoveries ranged from 93.8 to 128.7%, and the method was shown to be stable even when the samples were stored for 24 days. Prospective applications of this method in 909 participants also indicated good performance with a sensitivity of 100% and a specificity of 99.6%. CONCLUSIONS: We have developed a fast, high throughput and reliable method for screening of ß-thalassemia and hemoglobinopathy in children and adults, which is expected to be used as a first-line screening assay.

Resting-state coupling between HbO and Hb measured by fNIRS in autism spectrum disorder.

To distinguish between children with autism spectrum disorder (ASD) and typically developing (TD) children, we have uncovered a new discriminative feature, hemoglobin coupling. Functional near-infrared spectroscopy (fNIRS) was used to record resting-state hemodynamic fluctuations in the bilateral temporal lobes in 25 children with ASD and 22 TD children, in which the coupling between low frequency oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (Hb) fluctuations was evaluated by Pearson correlation coefficient. The results showed significantly weak coupling in children with ASD in both the left and right, and throughout the whole temporal cortex. To explain this observation, a simulation study was performed using a balloon model, in which we found four related parameters could impact the coupling. This study suggested that hemoglobin coupling might be applied as a new cerebral hemodynamic characteristic for ASD screening or diagnostics.

The Contribution of Diet Therapy and Probiotics in the Treatment of Sarcopenia Induced by Prolonged Immobilization Caused by the COVID-19 Pandemic.

The prolonged immobilization associated with COVID-19 infection and the restrictions imposed by the pandemic have determined major changes in physical activity and eating habits, with a negative impact on physical performance. This study monitored non-pharmacological interventions (diet therapy and probiotics) in managing sarcopenia for patients with recent SARS-CoV-2 history (14 days). A prospective study was performed on 200 patients (between December 2020−December 2021), with SPPB score < 9, randomly divided into: Group K­DP (93 patients) with dietary therapy (protein 1.2−1.5 g/kg) and probiotics for two months; and Group K­non-DP (107 patients) without diet therapy and probiotics. All patients were included in a specific physical training program (40 min), three sessions per week. Skeletal muscle index (SMI), serum albumin, and hemoglobin were determined. The SMI was initially low for both groups without significant statistical differences (6.5 ± 0.52 kg/m2 for Group K­non-DP vs. 6.7 ± 0.57 Kg/m2 for Group K­DP, p = 0.135). After two months, significant difference between initial and final SMI values was determined for Group K­DP (6.92 ± 0.50 kg/m2 vs. 6.77 ± 0.56 kg/m2, p = 0.048). In Group K­DP, at end of study, were more patients with normal SMI (n = 32 → N = 70) values (p < 0.001) and fewer sarcopenia patients (p < 0.001). The initial serum albumin means values in the two groups (Group K­non-DP, 4.17 ± 1.04 g/dL, and Group K­DP, 3.95 ± 0.98 g/dL) were not statistically significantly different (p = 0.122). The hemoglobin level improved significantly following a hyper protein diet enriched with pro-biotics (p = 0.003). Diet therapy, consisting of increased protein intake and specific probiotics and specific physical therapy, demonstrated superiority in improving the functional status of patients with recent COVID-19 infection.

Hb Alessandria [ß37(C3)Trp→Leu; HBB: c.113G>T]: a Novel Variant on the ß-Globin Chain with Slightly Increased Affinity for Oxygen Detected by Capillary Electrophoresis.

We report a novel mutation on the ß-globin gene in a 68-year-old woman of Sicilian origin living in Alessandria, Italy. This mutation produces a hemoglobin (Hb) variant of Hb A that was detected by the capillary electrophoresis (CE) method during measurement of Hb A1c. The variant Hb did not separate from Hb A using different high performance liquid chromatography (HPLC) instruments. Direct DNA sequencing revealed a G>T transversion at codon 37 and subsequent substitution of a tryptophan residue for a leucine residue. The new Hb variant was named Hb Alessandria [ß37(C3)Trp→Leu; HBB: c.113G>T]. The p50 value was slightly decreased while the stability test at 37 °C in isopropyl alcohol and the main erythrocyte parameters were normal. Overall, the patient appeared clinically normal.

Epidemiological and molecular study of hemoglobinopathies in Mauritanian patients.

BACKGROUND: Hemoglobinopathies, inherited disorders of hemoglobin (Hb), are the most common hereditary monogenic diseases of the red cell in the world. Few studies have been conducted on hemoglobinopathies in Mauritania. Therefore, the aim of this work is to establish the molecular and epidemiological basis of hemoglobinopathies in a cohort of Mauritanian patients and to determine the haplotype of the ß-globin gene cluster in sickle cell subjects. METHODS: The molecular screening of Hb disorders in 40 Mauritanian patients was done by a polymerase-restriction fragment length polymorphism (RFLP) for the sickle cell disease (SCD) mutation, a PCR/sequencing method for ß-thalassemia mutations, and by the multiplex polymerase chain reaction method for the α-thalassemia. The exploration of eight polymorphic sites (SNPs) within the ß-globin gene cluster was conducted by PCR/RFLP method, to identify the HbS haplotypes from the sickle cell subjects. RESULTS: The epidemiological study of our patients showed a high incidence in the Senegal River area (52.5%) and a high ethnic prevalence for the Heratin (47.5%) and the Pular (35%). Molecular study allowed us to identify eight different mutations in our sample analyzed. They are respectively: HbS (HBB:c.20A>T) (68.75%), Cd44 -C (HBB:c.135delC) (8.75%), -29A>G (HBB:c.-79A>G) (4.8%), -α-3.7 (g.34164_37967del3804) (3.75%), IVS-II-849A>G (HBB:c.316-2A>G) (2.25%) and Cd24T>A (HBB:c.75T>A), Hb Siirt (HBB:c.83C>G) and HbC (HBB:c.19G>A) each with (1.25%). Six different haplotypes are being explored among the SCD subjects with the Senegal haplotype as the most prevalent (66.7%), followed by Benin (10%), Arab-Indians (6.7%), Bantu (3.3%), and two atypical haplotypes. CONCLUSION: Our findings enrich the epidemiological data in our population and could contribute to the establishment of a strategy of prevention and management through screening, genetic counseling, and prenatal diagnosis of Hemoglobinopathies in the Mauritanian population.

Hb Kirikiriroa [α57(E6)Gly→Cys; HBA1: c.172G>T]: A Novel Unstable α-Globin Variant with Oxidized Derivatives Interfering with Hb A1c.

We report the identification of a novel hemoglobin (Hb) variant [α57(E6)Gly→Cys; HBA1: c.172G>T], to be referred to as Hb Kirikiriroa. The variant was detected in five subjects from two families, with familial relationship established between the families following diagnosis. A persistently elevated Hb A1c over a 1-year period prompted hemoglobinopathy screening in an adolescent male of New Zealand (NZ) European descent (case 1). Capillary electrophoresis (CE) revealed the variant was negatively charged and susceptible to oxidation, with multiple abnormal peaks detected (0.4-5.1% total Hb). Hb A1c analysis by cation exchange high performance liquid chromatography (HPLC) was the first indication of the variant in a pregnant female of NZ European descent (case 2). Cases 1 and 2 had normal complete blood counts. Isopropanol stability testing provided evidence the variant was unstable. We herein describe the characterization of Hb Kirikiriroa and clinical significance of the variant for interference with Hb A1c analysis by CE and cation exchange HPLC.

Hb Kalundborg [ß79(EF3)Asp→Glu; HBB: c.240C>a], a Possible Low-affinity Hemoglobin Variant Detected during Hb A1c Measurement.

A previously unknown hemoglobin (Hb) variant was detected during measurement of glycosylated Hb (Hb A1c) after the introduction of a new high performance liquid chromatography (HPLC) apparatus. Subsequent DNA sequencing revealed a heterozygous single nucleotide substitution at codon 79 (C>A) on the ß-globin gene changing an amino acid [ß79(EF3)Asp→Glu; HBB: c.240C>A]. The new Hb variant was named Hb Kalundborg after the place of origin of the proband. Heterozygosity for this mutation appears to have no clinical significance in itself except for a possibly slightly lower oxygen affinity. However, it interferes with Hb A1c measurement by HPLC, causing a falsely high Hb A1c concentration when using the G11 apparatus with clinical implications possibly to follow.

Identification of a rare compound heterozygous hemoglobin variant ß0-thal [ß17(A14) Lys>Stop, HBB: c.52A>T] and Hb J-Lome [ß59(E3) Lys>Asn, HBB: c.180G>C].

BACKGROUND: HbA1c is the validated biomarker for glycemic management in diabetic individuals. Here, we report a compound heterozygote for ß0-thal and Hb J-Lomeand evaluate its effect on HbA1c measurements. METHODS: A 51-year-old female was suspected of harboring a hemoglobin variant following no value of HbA1c levelby Arkray HA-8180 V (48s HbA1c mode), abnormal hematological data, and abnormalhemoglobin analysison capillary electrophoresis (Capillarys 2 Flex Piercing, Hb program). Sanger sequencing of the α and ß genes was subsequently performed on the proband.HbA1c was reanalyzed using D10 (Bio-Rad), Capillarys 2 Flex Piercing (Sebia), and Roche Cobas c501 (Roche Diagnostics). RESULTS: Sanger sequencing identified a compound heterozygote for ß0-thal [ß17(A14) Lys > Stop, HBB: c.52A > T] and Hb J-Lome [ß59(E3) Lys > Asn, HBB: c.180G > C].HbA1c values ⁣⁣determinedby D10, Capillarys 2 Flex Piercing (HbA1c program), and Roche Cobas c501were 2.3%, no HbA1c value, and 5.1 (32 mmol/mol), respectively. During pedigree analysis, the son of the proband was found to have normal blood glucose (5.55 mmol/L), decreased HbA1c (3.6%, 16 mmol/mol)by Arkray HA-8180 V (48s HbA1c mode), an abnormal band on the electrophoretogram of Capillarys2 (Hb program), and the Hb J-Lome mutation in the ß globin gene.Subsequently, HbA1c values ⁣⁣determinedby D10, Capillarys 2 Flex Piercing (HbA1c program), and Roche Cobas c501 were4.0% (20 mmol/mol), no HbA1c value, and 5.0 (31 mmol/mol), respectively. CONCLUSION: Atypically low HbA1c levels or a discrepancy between blood glucose and HbA1c levels should raise concerns about hemoglobin variations.