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Hemoglobin is an iron-carrying oxygen transport protein protein in red cells in the blood of mammals and other animals. Hemoglobin consists of iron which is the carrier of O2. High and abnormal hemoglobin levels occur due to hemoconcentration due to dehydration. The number of red blood cells and hemoglobin molecules is not always increasing and decreasing simultaneously, for example the decrease in red blood cells along with slightly elevated or normal hemoglobin levels occur in cases of pernicious anemia, as well as slightly elevated or normal hemoglobin levels of hemoglobin decreases, occurs in iron deficiency anemia. The purpose of this research is to know the effect of green bean extract on changes of hemoglobin (Hb) level in Pregnant Women. The research design used was pre experimental research. The population in detail is all Pregnant Women, with acidental sampling technique in obtaining a sample of 16 people. The research instrument used is observation sheet and digital hemoglobin gauge and statistic test used is T test. The result of research of hemoglobin level before giving of green bean has average value (mean) is 10,494 and hemoglobin level after giving of green bean has average value (mean) is 11.238 this indicates an increase of hemoglobin level in student result of research done shows that there is an increase of Hb level in get p value 0,756 and 0,89. Then the T.Test data distribution test can be concluded p value

Cigarettes are processed tobacco using or without addictive substances. The increasing of hemoglobin in smokers due to the content of carbon monoxide causes hemolysis of erythrocytes that is stronger than oxygen, so that hemoglobin increases. In addition to smoking, the society's habit is about coffee consumption. Coffee is a beverage with high polyphenols. The decreasing of hemoglobin occurs when drinking too much coffee. It will reduce the absorption of iron and erythrocytes ability to deliver oxygen from the lungs to all tissues in the body, therefore the hemoglobin will decrease. One of the laboratory tests that is used to see hemoglobin levels in smokers and coffee consumers is the POCT method of hemoglobin examination. The purpose of this study was to analyze the comparison of the effect between smoking and coffee consumption on hemoglobin levels in adolescents on the streets of Mejenan Gang 3 Mojoroto Kediri. The method that is used in this research is comparative study and the sampling technique that is used purposive sampling with a sample size of 40 respondents. The results show that 10 adolescents (50%) had abnormal hemoglobin levels and 10 adolescents (50%) had normal hemoglobin levels. 5 teenagers (25%) had abnormal hemoglobin levels and 15 (75%) normal hemoglobin levels. Based on statistical tests, the results obtain p-value 0.423 and> 0.05. So it can be concluded that there is a moderate effect between cigarettes and coffee on hemoglobin levels in adolescents on Mejenan Street Gang 3 Mojoroto Kediri.

Background: Glycated Hemoglobin A1c (HbA1c) assay is most widely used in diabetic patients for assessing long-term control of glycemia. The presence of hemoglobin variants may be an incidental finding and can interfere with HbA1c measurements. The aim of the present study is to investigate the prevalence and impact of interference of different abnormal hemoglobin variants on HbA1c measurements during routine HbA1c testing. Methods: A total of 12,092 HbA1c samples were collected from January to August 2018. HbA1c quantification was carried out on a Variant II Bio-Rad’s HPLC analyzer. Abnormal chromatograms were further analyzed using the extended-run high-pressure liquid chromatography (HPLC) analysis in the A2/F mode. Results: The samples were examined for presence of abnormal variants. Samples producing abnormal chromatograms were further analyzed in A2/F mode to characterize hemoglobin variants. Abnormal variants were identified in 126 (1%) samples, and 74 (0.59%) sickle cell traits (SCT) were the most common variant in our findings. Moreover, 30 (0.24%) cases were eluted in the variant window in A1c mode, which on further analysis were found to be Hb E & Hb D traits. Furthermore, 3 (0.02%) cases were eluted at a RT

Sickle cell disease (SCD) is the most common inherited blood disorder in the United States, and a global health problem. Pathological features of the abnormal hemoglobin (HbS) result in 2 hallmarks of the disease - recurrent episodes of acute microvascular occlusion and chronic hemolytic anemia - that inflict continuous and insidious damage to multiple organs. With improved childhood survival, SCD in adults has evolved into a chronic degenerative disease with underlying damage to multiple organs including the heart and lungs. Cardiopulmonary complications, including cardiomyopathy, diastolic dysfunction, pulmonary hypertension (PH), and sudden cardiac death are the most common causes of morbidity and mortality. Awareness of the sickle-related cardiovascular phenotypes is important for screening, early diagnosis, and intervention of cardiac complications in this disorder.

Sickle cell disease (SCD) is a common hemoglobinopathy, secondary to alterations in the β globin chain, resulting in an abnormal hemoglobin variant named as hemoglobin S. These disorders show a wide phenotypical spectrum, and the prevalence of these disorders has significantly changed over the time because of multiple factors such as migration. We report a case of a 17-year-old black male, born in Gambia, diagnosed with sickle cell disease, who presented an associated mutation only described in a Japanese family (Oshima et al., 1996).

As it was mentioned in the previous paper, we observed the mechanism of action the interesting drug, first synthesized back in 1869 for the first time, called Hydroxyurea. A century later, phase I and II trials began to test its safety in humans with solid tumors. It was first approved by the FDA in 1967 for the treatment of neoplastic diseases and is presently approved for the treatment of melanoma, resistant chronic myelocytic leukemia (CML), and recurrent, metastatic testicular and ovarian cancer. Sickle cell disease is a genetic disorder that decreases life expectancy by 25 to 30 years. Individuals are diagnosed with sickle cell disease if they have one of several genotypes that result in at least half of their hemoglobin being hemoglobin S (HbS). Sickle cell anemia refers specifically to the condition associated with homozygosity for the Hb S mutation (Hb SS). Several other hemoglobin mutations, when occurring with an Hb S mutation, cause a similar but often milder disease than sickle cell anemia. In addition to reduced life expectancy, patients with sickle cell disease experience chronic pain and reduced quality of life. Painful crises, also known as vaso-occlusive crises, are the most common reason for emergency department use and hospitalization, and acute chest syndrome is the most common cause of death. Prior to the approval of hydroxyurea for use in sickle cell disease, patients with this condition were treated only with supportive therapies. These measures included penicillin in children to prevent pneumococcal disease, routine immunizations, and hydration and narcotic therapy to treat painful events. Red blood cell transfusions increase the blood’s oxygen carrying capacity and decrease the concentration of cells with abnormal hemoglobin, but chronic transfusion therapy predictably leads to iron overload and alloimmunization. Therapies such as hydroxyurea that raise fetal hemoglobin (Hb F, α2γ2) levels are promising because they effectively lower the concentration of Hb S within a cell, resulting in less polymerization of the abnormal hemoglobin.Hydroxyurea’s efficacy in sickle cell disease is generally attributed to its ability to raise the levels of Hb F in the blood; however, the mechanisms by which it does so are unclear. Early studies suggested that hydroxyurea is cytotoxic to the more rapidly dividing late erythroid precursors, resulting in the recruitment of early erythroid precursors with an increased capacity to produce HbF.

ntroduction: Tuberculosis (TB) is a contagious infectious disease caused by mycobacterium tuberculosis. Indonesia is a country with the third largest case of pulmonary tuberculosis in the world. The purpose of this study is to determine the description of hemoglobin levels in patients with pulmonary tuberculosis who are undergoing anti-tuberculosis therapy in Pancur Batu Health Center, Deli Serdang Regency.Method:The research method is descriptive with the study population being all patients with pulmonary tuberculosis who are undergoing anti-tuberculosis therapy, and a sample of 21 respondents. Result: Based on the results of the analysis, it is known that there is an effect of green color therapy on changes in the level of student anxiety in facing exams.Discussion: The results of the study based on age obtained that most respondents aged between 60-72 years were 8 respondents (38.1%), most respondents were male as many as 14 respondents (66.7%) with abnormal hemoglobin levels 12 respondents (87,1%). The conclusion of this study is the results of research based on age there are the most respondents aged 60-72 years, male sex with more hemoglobin levels that are not normal (anemia).

Hemoglobin M (HbM) is a group of abnormal hemoglobin variants that form methemoglobin, which leads to cyanosis and hemolytic anemia. HbM-Milwaukee-2 is a rare variant caused by the point mutation CAC>TAC on codon 93 of the hemoglobin subunit beta (HBB) gene, resulting in the replacement of histidine by tyrosine. We here report the first Korean family with HbM-Milwaukee-2, whose diagnosis was confirmed by gene sequencing. A high index of suspicion for this rare Hb variant is necessary in a patient presenting with cyanosis since childhood, along with methemoglobinemia and a family history of cyanosis.

Hemoglobinopathies are a group of hereditary hemolytic anemias common in the countries of the Mediterranean, Southeast Asia and Africa, where malaria was previously common. Due to population migration and an increase in the number of mixed marriages, hemoglobinopathies are also relevant to Russia. Among the Russian Federation's subjects, the Republic of Dagestan is the most endemic region for the incidence of hemoglobinopathies. This study aimed to identify the spectrum of mutations in patients with hemoglobinopathies living in the Republic of Dagestan. The research was approved by Independent ethic committee and the academic board of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology (Moscow, Russia). Material from 100 patients was sent for molecular genetic research to the Laboratory of Molecular Biology, Federal State Budget Scientific Institution Scientific Research Center for Surgery named after Dmitry Rogachev. Genetic variants of the genes of the a- and b-globin clusters were determined using multiplex ligase-dependent amplification of samples and Sequencing by the Sanger method. Eighteen genetic variants with different frequencies were detected. The mutation frequency of the b-globin cluster was 62.5%, the a-globin cluster was 23.2%, and the variants leading to the appearance of abnormal hemoglobin were 14.3%. The five most common genetic variants among this cohort were also identified: CD8(-AA) and IVSI-110 (G>A), -(a) 3.7 and -(a) 20.5 and the CD6 variant GAG>GTG [Glu>Val] leading to abnormal hemoglobin S.

BACKGROUND: Thalassemia is a disorder of inherited blood and inticated by the abnormal hemoglobin. Transfusion and iron chelation are part of thalassemia management. Iron chelating agent reduces complications due to the excess iron as a result of repeated transfusions, hence, increasing the survival rate. However, prolonged intake of iron chelating agent may increase the risk of renal function impairment. To date, evaluation of renal function in children with β-thalassemia in Medan has never been reported. The objective of this study was to evaluate renal function and other factors in children with β-thalassemia.METHODS: Fourty-five children with β-thalassemia was recruited in this study. Renal function, represented by estimated glomerular filtration rate (eGFR)and serum ferritin levels were examined. The measurement of eGFR was using Schwartz method.RESULTS: Decreased eGFR observed in some the children (2 patients) with β-thalassemia major treated with iron chelating agent. None of the factors examined had association with serum creatinine level. Children's age and duration of iron chelating agent intake had positive correlation with their eGFR (r=0.506, p

Background Obtaining postoperative laboratory studies after primary reverse shoulder arthroplasty (RSA) is a common practice. However, justification of this practice remains unclear. This study assesses the utility of routine postoperative laboratory studies in RSA. Methods The electronic medical records of 369 patients who underwent RSA over 10 years were retrospectively reviewed. A total of 213 patients qualified for analysis. Primary outcomes were intervention related to abnormal laboratory values, length of stay, and 90-day emergency department visits/readmissions. Multivariate logistic regression analysis was performed to identify risk factors associated with abnormal laboratory values and postoperative visits/readmissions. Results Of 213 patients analyzed, 188 (88.7%) had abnormal postoperative laboratory values: 69% had an abnormal hemoglobin (Hgb) or hematocrit level, but only 12% underwent interventions. Lower preoperative Hgb was a significant predictor of receiving a transfusion. A significant association existed between abnormal postoperative electrolyte and creatinine levels with lower body mass index (BMI) and higher Charlson Comorbidity Index (CCI). Only 4 patients (1.8%) received non–transfusion related intervention. Emergency department visits were not statistically different between patients with positive or negative laboratory tests (P = .73). Conclusion Because 87.3% of laboratory studies did not influence patient management, we recommend against routine testing for primary RSA. This study demonstrates that the practice of obtaining routine postoperative laboratory studies is not justified. We recommend selectively obtaining a postoperative basic metabolic profile in patients with increased American Society of Anesthesiologists classification and/or CCI with a lower BMI. We also recommend selectively ordering postoperative complete blood count in patients with a lower preoperative Hgb.

Se'i/nu is one of the traditions of the local community on the island of Timor. The research objective was to prove the relationship between the roasting tradition (se'i/nu) with the hemoglobin level and the process of uterine involution in postpartum women. The research design was analytical with an observational approach. The sample consisted of 42 respondents obtained through total sampling. The independent variable was the roasting tradition (se’i/nu) and the dependent variables were hemoglobin level and maternal uterine involution. The method used to measure the roasting tradition (se’i/nu) was an observation sheet. To measure the hemoglobin level, we used a laboratory check and to measure uterine involution, we conducted a physical examination and used an observation sheet. The results showed that the largest percentage of hemoglobin levels in postpartum mothers was among those that did the roasting tradition (se'i/nu) with an abnormal hemoglobin level of 66.66% (22 people). The puerperal women who did the tradition of roasting (se'i/nu) obtained high uterine fundus and the abnormal mothers made up the largest percentage of 69.70% (23 people). There was a correlation between the roasting tradition (se'i/nu) and maternal hemoglobin level (p=0.025) and there was also a correlation between the roasting tradition (se'i/ nu) with the process of maternal uterine involution (0.00). The conclusion is that there is a prolonged uterine involution process and that the low hemoglobin levels in the puerperium may be due to exposure to chemical susceptibility as a result of inhaling polluted air due to the se'i/nu process.

The clinical consequences of many abnormal hemoglobins (Hbs) interacting with α- or β-thalassemia (α- or β-thal) or other hemoglobinopathies have not been described. We evaluated a 75-year-old Thai woman and her 45-year-old daughter. Hematological data was obtained on an automated cell counter. Hemoglobin (Hb) analysis was carried out using high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) assays. Mutations and globin haplotypes were identified by appropriated DNA techniques. The proband presented with moderate anemia and inclusion bodies in most of the red blood cells (RBCs), while altered RBC parameters were absent in her daughter. Hemoglobin analysis showed an abnormal Hb peak only in the proband. DNA analysis identified a G>T substitution at codon 31 of the α1-globin gene, corresponding to Hb Prato [α31(B12)Arg→Ser (HBA1 or HBA2 c.96G>T or C)] in both subjects. The α-thal-1 [- -SEA (Southeast Asian)] deletion was also identified in the proband, but not in her daughter. These mutations could be identified using newly developed allele-specific polymerase chain reaction (ASPCR) assays. The α haplotypic analysis demonstrated the Thai Hb Prato allele was associated with haplotype [+ - S + - + -] [the S represents the inter ζ hypervariable region (HVR)]. The combination of the unstable Hb Prato with α-thal-1 result in α-thal intermedia (α-TI) phenotypes. A simple DNA method is essential for detection, and a haplotypic α-globin gene cluster are presented.

formados pela combinação de duas cadeias polipeptídicas do “tipo α” com duas cadeias do “tipo β”, sendo Hb A1, Hb A2 e Hb Fetal os três principais tipos de hemoglobinas no adulto normal. As hemoglobinopatias são doenças causadas por mutações que afetam os genes de globinas, que resultam em alterações estruturais e/ou funcionais das moléculas de hemoglobina. Dentre as hemoglobinas variantes, as mais frequentes na população brasileira são a hemoglobina S e C. O objetivo é detectar hemoglobinas anormais em uma população acadêmica de Alfenas-MG. Para a realização do estudo, foram coletadas 336 amostras de sangue periférico, hemolisadas com saponina e clorofórmio. Em seguida, foi realizada a eletroforese de hemoglobina em pH alcalino para qualificação de hemoglobinas normais e grande parte das anormais. A confirmação da hemoglobina S foi feita pela prova de falcização. Do total de amostras analisadas, 97,62% (n=328) apresentam perfil eletroforético compatível com hemoglobinas AA e 2,38% (n=8) compatível com hemoglobinas AS (traço falciforme). No Brasil, a prevalência média de Hb AS é próxima de 2% na população total. Portanto, os resultados encontrados reafirmam a média encontrada na população brasileira de pessoas com o traço falciforme.

Background Sickle cell disease is the most common monogenic disorder in humans and is a major public health concern in sub-Saharan Africa. In Benin, the prevalence of sickle cell disease is estimated to be 4.8%. Our study aimed to describe the prevalence of hemoglobin abnormalities in an apparently healthy Benin population. Methods One thousand four hundred and eighty-three men and women, apparently in good health after medical screening, were tested for hemoglobin abnormalities by hemoglobin electrophoresis and the Emmel test. Subjects who were found to have homozygous or double heterozygous hemoglobin abnormalities, were re-sampled and a confirmation hemogram and hemoglobin electrophoresis test by capillary electrophoresis was performed. Results Our study population was predominantly male (97.7%) with an average age of 21.3 years. 1390 subjects reported that they did not know their hemoglobin electrophoresis status. Hemoglobin electrophoresis profiles found were as follows: 1077 (72.6%) AA (normal), 238 (16.1%) AS, 161 (10.9%) AC, 3 (0.2%) SC, 4 (0.2%) CC and 0 (0%) SS. The 406 subjects with abnormal hemoglobin had balanced somatic growth, with general physical examination results showing no abnormalities. In the seven subjects with major sickle cell syndrome or hemoglobinosis (SC and CC), their values of various hemogram parameters were normal apart from the discreet presence of microcytic anemia. Conclusion Our study highlights the need for increased routine testing of hemoglobin abnormalities and newborn screening for sickle cell disease in order to enhance early disease detection, prevention and comprehensive care.

Objectives Hemoglobinopathies are inherited transition blood diseases associated with globin chains of the hemoglobin. However many mutations have been defined, there may be many of them not defined yet. We here report the first case of those mutations, named Hb G-Norfolk in Turkey. Case presentation A 15 years-old male patient with erythrocytosis was referred to our laboratory for the evaluation of hemoglobinopathy. In chromatographic analysis, an unidentified peak was observed. A similar identification for variant Hb could not be obtained from High-Performance Liquid Chromatography (HPLC) analyzer’s data library. No definitive diagnosis could also be made by different analyzer. Family screening and molecular genetic DNA sequence analysis were carried out. Conclusions Although there were not found any beta gene mutation of neither the patient nor his family, analyses of alpha genes A1 and A2 were performed and abnormal hemoglobines were detected for all of them. This change in the HbA2 gene was at codon85 GAC>AAC (Asp>Asn) in the heterozygous state, known as Hb G-Norfolk [HbA2:c256G>A p.Asp85Asn] based on HbVar database. Abnormal Hb bands detected by HPLC with clinical findings such as erythrocytosis or cyanosis should be investigated by sequence analysis to corroborate alpha and/or beta-globin gene mutations for avoiding misdiagnosis and misinterpretation.

Background Anemia or low hemoglobin can increase the risk of stroke. However, the association between hemoglobin and outcomes after stroke is uncertain. In this study, we aimed to investigate the association between hemoglobin and clinical outcomes, including mortality, poor functional outcome, stroke recurrence, and composite vascular events at 1 year. Methods and Results We included the patients diagnosed with acute ischemic stroke or transient ischemic attack from the Third China National Stroke Registry. We used the Cox model for mortality, stroke recurrence, and composite vascular events and the logistic model for the poor functional outcome to examine the relationship between hemoglobin and clinical outcomes. In addition, we used the restricted cubic spline to evaluate the nonlinear relationship. This study included 14 159 patients with acute ischemic stroke or transient ischemic attack. After adjusted for potential cofounders, both anemia and high hemoglobin were associated with the higher risk of mortality (hazard ratio [HR], 1.73; 95% CI, 1.39–2.15; HR, 2.71; 95% CI, 1.95–3.76) and poor functional outcome (odds ratio [OR], 1.36; 95% CI, 1.18–1.57; OR, 1.42; 95% CI, 1.07–1.87). High hemoglobin, but not anemia, increased the risk of stroke recurrence (HR, 1.37; 95% CI, 1.05–1.79) and composite vascular events (HR, 1.41; 95% CI, 1.08–1.83). There was a U‐shaped relationship between hemoglobin and mortality and poor functional outcome. Conclusions Abnormal hemoglobin was associated with a higher risk of all‐cause mortality, poor functional outcome, stroke recurrence, and composite vascular events. More well‐designed clinical studies are needed to confirm the relationship between hemoglobin and clinical outcomes after stroke.

Background and Objectives: Sickle cell disorder (SCD) is a paradigmatic example of a complex monogenic disorder. SCD is characterized by the production of abnormal hemoglobin, primarily in the deoxygenated state, which makes erythrocytes susceptible to intracellular hemoglobin polymerization. Functional studies have affirmed that the dysregulation of miRNAs enhances clinical severity or has an ameliorating effect in SCD. miRNAs can be effectively regulated to reduce the pace of cell cycle progression, to reduce iron levels, to influence hemolysis and oxidative stress, and most importantly, to increase γ-globin gene expression and enhance the effectiveness of hydroxyurea. Results: This review highlights the roles played by some key miRNAs in hemoglobinopathies, especially in hematopoiesis, erythroid differentiation, and severity of anemia, which make miRNAs attractive molecular tools for innovative therapeutic approaches. Conclusions: In this era of targeted medicine, miRNAs mimics and antagomirs may be promising inducers of HbF synthesis which could ameliorate the clinical severity of SCD.

Sickle cell anemia (SCA) is a severe disease characterized by anemia, acute clinical complications, and a relatively short life span. In this disease, abnormal hemoglobin makes the red blood cells deformed, rigid, and sticky. Fetal hemoglobin (HbF) is one of the key modulators of SCA morbidity and mortality. Interindividual HbF variation is a heritable trait that is controlled by polymorphism in genes linked and unlinked to the hemoglobin β gene (HBB). The genetic polymorphisms that determine HbF levels are known to ameliorate acute clinical events. About 190 well-characterized homozygous SCA patients were included in this study. Complete blood count (CBC), high-performance liquid chromatography (HPLC), and clinical investigations were obtained from patient's records. Severity scores were determined by using the combination of anemia, complications, total leucocyte count, and transfusion scores. HBG2 rs7482144 polymorphism was genotyped by using the polymerase chain reaction and restriction fragment length polymorphism. The association between HBG2 rs7482144 polymorphism and HbF levels as well as the disease severity of SCA were assessed. SCA patients carrying TT genotype were found to have higher HbF levels. In addition, SCA patients with increased severity showed significantly lower levels of hemoglobin, HbF, and hematocrit values. However, the genotypes of HBG2 rs7482144 polymorphism were not found to be associated with the risk of disease severity. In summary, this study demonstrated that HBG2 rs7482144 polymorphism is linked with HbF levels, but it does not affect disease severity. The sample sizes used and the pattern of association deduced from our small sample size prevents us from extrapolating our findings further.

Background: HPLC is one of the most important tools for accurate diagnosis of hemoglobinopathies and thalassemias. The advantage of the HPLC system is the excellent resolution, reproducibility &quantification of several normal and abnormal hemoglobin. Results: BIO RAD Variant II analyzer was used. Sickle cell syndromes including double heterozygous states accounted for 56.13% of total cases. HbSS, HbS/β0-th, HbS/β+–th β-thal trait comprises 29%, 6.5%, 5.1%& 10% of total cases respectively with mean MCV (fl) = 84, 68,71,64 respectively. The Mean HbA2 for β-thal trait, HbE trait &HbE-β thal showed 5.1 ± 1.1, 19 ± 9 & 24 ± 8 respectively. HbF is increased in 8.6% case (excluding SC syndromes & β-thal disorders), of these 5.5% were infants & 12 cases of Aplastic Anemias. Peak P2 >7% (2.4% cases) was seen in uncontrolled diabetes mellitus which on quantification showed HbA1C = 8 ± 2.1 mmol/L. Discussion: HPLC in correlation with CBC parameters & family studies can aid in the diagnosis of majority of Hemoglobinopathies and thalassemic syndrome. The CBC & HPLC parameters of the present study are in good correlation with the research conducted by Tejinder Sing, RiouJ & Alla Joutovsky. Present study showed HPLC comprehensively characterizing HbS, A, A2, F, S, C, D from each other & was also applicable for the quantification of HbA1c for the monitoring of Diabetes Mellitus. Conclusion: The merits of HPLC are small quantity of sample required, economical, less TAT, accurate categorization of HbS, HbA2 & F. But one has to be aware of the limitations and problems associated with this method due to variant hemoglobin within the same retention windows. The present findings show HPLC as an excellent & powerful diagnostic tool for the direct identification of hemoglobin variants with a high degree of precision in the quantification of normal and abnormal hemoglobin fractions.

Methemoglobinemia (Meth) is a rare hemoglobin (Hb) disorder with distinguished clinical features and complex pathophysiology. We present a three-year-old female who was diagnosed with congenital methemoglobinemia when she presented with peri-oral cyanosis and profound oxygen desaturation in the 20-30% range. This patient also had elevated deoxyhemoglobin (HHb) not explained by methemoglobinemia alone; the low pulse oximetry (SpO2) reading suggested a rightward-shift oxyhemoglobin (O2Hb) dissociation curve, which is the opposite of that expected in methemoglobinemia. This, along with evidence of hemolysis, raised the possibility of a concomitant low-oxygen affinity hemoglobinopathy, which could explain elevated HHb. Hemoglobin electrophoresis identified an abnormal hemoglobin variant which was categorized as heterozygous for unstable beta globin variant. The patient responded well to one dose of methylene blue, vitamin C, supportive oxygen (O2) therapy, and IV hydration and was discharged with a baseline of 50-60% SpO2 on room air. We are reporting this case along with a brief review of the medical literature.

Sickle cell disease (SCD, OMIM #603903), an autosomal recessively inherited β-hemoglobinopathy, was the first human disorder delineated at a molecular level. The putative single nucleotide mutation in the HBB gene generates an abnormal hemoglobin species, which polymerizes in deoxygenated conditions causing irreversible changes in erythrocyte shape and function. Sickling erythrocytes are in turn responsible for microvascular vaso-occlusion, hemolysis and a systemic vasculopathy in patients. SCD has represented an attractive field for proteomic investigation since its methodological infancy. Clinically actionable biomarkers, especially for the prevention of cerebrovascular complications in children with the condition, are urgently needed and their discovery remains a major challenge. In this issue, Lance and colleagues report of their unbiased proteomic studies on samples from the participants of the landmark prospective, randomized, single-blind SIT trial (NEJM 2014). Their results reveal numerous brain-enriched plasma proteins specific for SCD, and for silent cerebral infarcts in this disorder, and further analyses highlight novel cellular mechanisms behind the brain damage in SCD. Although the goal of identifying reliable biomarker candidates for cerebrovascular complications could not be met, the dataset produced by the authors constitutes a significant contribution to the field and opens new horizons for further clinical and laboratory investigation.

Basic research on hemoglobin has been essential for understanding the origin and treatment of many hematological disorders due to abnormal hemoglobins. The most important of the hemoglobinopathies is sickle cell disease - Linus Pauling's “molecular disease” that gave birth to molecular medicine. In this review, I will describe the contributions of basic biophysical research on normal and sickle cell hemoglobin (HbS) to understanding the molecular pathogenesis of the disease and providing the conceptual basis for the various approaches to drug therapy that target HbS polymerization. Most prominent among these are the experimental results on the solubility of HbS as a function of oxygen saturation explained by the allosteric model of Monod, Wyman, and Changeux and the Gill-Wyman thermodynamic linkage relation between solubility and oxygen binding, the solubility of mixtures of HbS with normal or fetal hemoglobin explained by Minton's thermodynamic model, and the highly unusual kinetics of HbS polymerization explained by a novel double nucleation mechanism that also accounts for the aggregation kinetics of the Alzheimer's peptide. The HbS polymerization kinetics are of great importance to understanding the pathophysiology and clinical course, as well as guiding drug development for treating this common and severe disease. The article focuses primarily on experimental and theoretical results from my lab, so it is not a comprehensive review of the subject.

Sickle cell disease is a disorder of hemoglobin. The abnormal hemoglobin S disrupts blood flow, thereby resulting in acute painful sickle cell crisis. These episodes frequently prompt packed red blood cell transfusions to replace a patient's functional hemoglobin stores. Production of alloantibodies and autoantibodies to these transfusions can result in a rare, but serious, complication known as hyperhemolysis syndrome. Hyperhemolysis syndrome presents several challenges in regard to its acute management and the consequent difficulties in finding future compatible blood products. We report a case of recurrent hyperhemolysis syndrome. Both episodes occurred following orthopedic procedures, and the recurrent episode proved refractory to multiple treatments.

Sickle cell disease (SCD) is a hereditary disorder that leads to the production of an abnormal hemoglobin, hemoglobin S (HbS). HbS polymerizes in deoxygenated conditions, which can prompt red blood cell (RBC) sickling and leaves the RBCs more rigid, fragile, and prone to hemolysis. SCD patients suffer from a plethora of complications, ranging from acute complications, such as characteristic, frequent, and debilitating vaso-occlusive episodes to chronic organ damage. While RBC sickling is the primary event at the origin of vaso-occlusive processes, other factors that can further increase RBC transit times in the microcirculation may also be required to precipitate vaso-occlusive processes. The adhesion of RBC and leukocytes to activated endothelium and the formation of heterocellular aggregates, as well as increased blood viscosity, are among the mechanisms involved in slowing the progress of RBCs in deoxygenated vascular areas, favoring RBC sickling and promoting vascular occlusion. Chronic inflammatory processes and oxidative stress, which are perpetuated by hemolytic events and ischemia-reperfusion injury, result in this pan cellular activation and some acute events, such as stroke and acute chest syndrome, as well as chronic end-organ damage. Furthermore, impaired vasodilation and vasomotor hyperresponsiveness in SCD also contribute to vaso-occlusive processes. Treating SCD as a vascular disease in addition to its hematological perspective, the present article looks at the interplay between abnormal RBC physiology/integrity, vascular dysfunction and clinical severity in SCD, and discusses existing therapies and novel drugs in development that may ameliorate vascular complications in the disease. © 2021 American Physiological Society. Compr Physiol 11:1785-1803, 2021.

Hereditary hemolytic anemia caused by unstable hemoglobin is a rare pathology, characterized by variability of clinical manifestations. This disease is characterized by the hemolytic crises, which are frequently associated with infections or taking drugs that cause hemolysis. Age of debut depends on which of the globin chains mutation occurs. Among these diseases, hemolytic anemia associated with the presence of a structurally abnormal unstable hemoglobin with low oxygen affinity in the erythrocytes is a special group. With this type of abnormal hemoglobin, pulse oximetry demonstrates falsely low oxygen saturation of the blood, with increased oxygen delivery to the tissues. It is important to identify unstable hemoglobin in order to avoid the misinterpretation of low oxygen saturation during the pulse oximetry in emergency cases, surgeries or intensive therapy. The article presents an analysis of the family with hereditary hemolytic anemia due to unstable hemoglobin Cheverly. The main clinical and diagnostic markers of the disease are described in detail. Parents gave their permission for using personal data for clinical research and publications.

The hemoglobinopathies are a group of disorders passed down through families (inherited) in which there is abnormal production or structure of the hemoglobin molecule. They are among the most common inherited diseases around the world. Those that produce abnormal hemoglobin are called structural hemoglobinopathies while thalassemia is another type of disorder that is caused by a defect in the gene production of the globin chains. In a study ambispective comprising 1623 patients, 153 subjects showed an abnormal hemoglobin and 1470 with hypochromic and microcytic anemia, and of these 1470, 23 patients were studied for simultaneously α-thalassemias and structural hemoglobinopathies. Among the α-thalassaemia cases, 1282 cases (87.2%) were deletional α-thalassemia, 172 cases (11.7%) were non-deletional α-thalassemia, and 16 cases (1.1%) were deletional and non-deletional α-thalassamias simultaneously. Thus, approximately 12% of the cases were non-deletional α-thalassaemia. Clinical diagnosis, only 19 severe cases (1 hydrops fetalis and 18 instances of Hb H disease), 1200 thalassamias traits, and 160 thalassaemia silent carriers were recorded within the α-thalassaemia. Regarding structural hemoglobinopathies, there were only 2 cases of hemoglobinopathies with low oxygen affinity and 1 case of hemoglobin M; the remaining 150 were silent hemoglobinopathies. Non-deletional α-thalassaemia represented 12% of all α-thalassemias in our region; the most common deletion in our area was the 3.7-kb deletions, followed by Asian --(SEA) and --(FIL). The alterations responsible for non-deletional α-thalassaemia are most represented by the Hph and Hb Groene Hart and, in the case of structural hemoglobinopathies, Hb Le Lamentin and Hb J-Paris.

Sickle cell disease (SCD) is an inherited disease caused by the production of abnormal hemoglobin (Hb) S, whose deoxygenation-induced polymerization results in red blood cell (RBC) sickling and numerous pathophysiological consequences. SCD affects approximately 300,000 newborns worldwide each year and is associated with acute and chronic complications, including frequent painful vaso-occlusive episodes that often require hospitalization. Chronic intravascular hemolysis in SCD significantly reduces vascular nitric oxide (NO) bioavailability, consequently decreasing intracellular signaling via cyclic guanosine monophosphate (cGMP), in turn diminishing vasodilation and contributing to the inflammatory mechanisms that trigger vaso-occlusive processes. Oxidative stress may further reduce NO bioavailability in SCD and can oxidize the intracellular enzyme target of NO, soluble guanylate cyclase (sGC), rendering it inactive. Increasing intracellular cGMP-dependent signaling constitutes an important pharmacological therapeutic approach for SCD with a view to augmenting vasodilation, and reducing inflammatory mechanisms, as well as for increasing the production of anti-polymerizing fetal Hb in erythroid cells. Pharmacological agents under pre-clinical and clinical investigation for SCD include NO-based therapeutics to augment NO bioavailability, as well as heme-dependent sGC stimulators and heme-independent sGC activators that directly stimulate native and oxidized sGC, respectively, therefore bypassing the need for vascular NO delivery. Additionally, the phosphodiesterases (PDEs) that degrade intracellular cyclic nucleotides with specific cellular distributions are attractive drug targets for SCD; PDE9 is highly expressed in hematopoietic cells, making the use of PDE9 inhibitors, originally developed for use in neurological diseases, a potential approach that could rapidly amplify intracellular cGMP concentrations in a relatively tissue-specific manner. Impact statement Sickle cell disease (SCD) is one of the most common inherited diseases and is associated with a reduced life expectancy and acute and chronic complications, including frequent painful vaso-occlusive episodes that often require hospitalization. At present, treatment of SCD is limited to hematopoietic stem cell transplant, transfusion, and limited options for pharmacotherapy, based principally on hydroxyurea therapy. This review highlights the importance of intracellular cGMP-dependent signaling pathways in SCD pathophysiology; modulation of these pathways with soluble guanylate cyclase (sGC) stimulators or phosphodiesterase (PDE) inhibitors could potentially provide vasorelaxation and anti-inflammatory effects, as well as elevate levels of anti-sickling fetal hemoglobin.

Background: The District of Paal Merah, Jambi City, is a center for vegetable production for the Jambi City area and its surroundings. The aspect of excessive use of pesticides by farmers in the District of Paal Merah, Jambi City is a problem that needs attention, especially the practice of spraying which ignores aspects of safety and health of farmers that can lead to health problems both directly and indirectly for farmers. One of the long-term effects caused by exposure to pesticides is a decrease in hemoglobin levels and the amount of erythrocytes in the blood. Based on the report of the Payo Selincah Health Center in Jambi City, it was explained that in the District of Paal Merah, Jambi City in 2016 showed anemia sufferers reached 30% of the number of public health center visits. Objective: The purpose of this study was to describe and analyze the relationship of exposure to pesticides with hemoglobin levels and the number of erythrocytes in horticultural farmers in the District of Paal Merah, Jambi City. Method: This type of research is observational analytic with cross sectional study design conducted in the District of Red Paal with 80 respondents selected by purposive sampling. Data collection through interviews, observation, measurement of cholinesterase levels, measurement of hemoglobin levels and measurement of the amount of erythrocytes in the blood. Data analysis using chi-square test and logistic regression. Results: Based on the results of bivariate analysis, it was found that there were 3 independent variables related to hemoglobin levels, namely work period (p value = 0.005), frequency of spraying (p value = 0.007), pesticide dose (p value = 0.003, and no independent variables related to the number of erythrocytes. Conclusion: Based on research from 80 farmers who examined hemoglobin levels in the blood there were 73.8% of farmers who experienced abnormal hemoglobin levels, and 26.3% of farmers who experienced normal hemoglobin levels, and from 80 farmers who examined the amount of erythrocytes in blood is 22.5% of farmers who have an abnormal number of erythrocytes, and 77.5% of farmers have normal erythrocyte counts.

Hemoglobin A1c (HbA1c) is a widely utilized biomarker for the diagnosis and management of diabetes mellitus. Here, we describe an α1-globin chain hemoglobin variant and investigate its effect on HbA1c measurement. A 26-year-old pregnant woman was suspected to harbor a hemoglobin variant following HbA1c measurement during a routine prenatal examination using D10 (Bio-Rad). An oral glucose tolerance test (OGTT) was performed using an AU5800 clinical chemistry system (Beckman Coulter). HbA1c was reanalyzed using VII-T 2.0 (Bio-Rad), Capillarys 2 Flex Piercing (C2FP, HbA1c program, Sebia), Premier Hb9210 (Trinity Biotech), and Cobas c501 (Cobas Tina-quant Hemoglobin A1c Gen.3). Glycated albumin (GA) level was also quantified using an enzymic method GA Kit (Lucica GA-L, Japan). Hemoglobin analysis was performed using high performance liquid chromatography on the Bio-Rad Variant II (β-thalassemia short program) and capillary electrophoresis (Capillarys 2 Flex Piercing, Hb program). Sanger sequencing of α and β genes was also conducted. HbA1c was initially measured at 16.0% (151 mmol/mol) using the D10 (Bio-Rad). Her OGTT result was normal. Subsequently, HbA1c values determined by VII-T 2.0, C2FP, Premier Hb9210, and Cobas c501 were 4.8% (29 mmol/mol), 4.9% (30 mmol/mol), 4.6% (27 mmol/mol), and 4.8% (29 mmol/mol), respectively. The glycated albumin level was 12.3% (reference: 10.8 ∼ 17.1%). Hemoglobin analyzed using CE and HPLC revealed an abnormal hemoglobin. By Sanger sequencing, we identified a transition mutation in the α1 gene Hb Shantou [α127(H10)Lys > Glu; HBA1: c.382 A > G]. Clinically silent variants may interfere with HbA1c determination by common methods.

Aims The glycated hemoglobin (HbA1c) test can be unreliable in the presence of hemoglobinopathies. The co-existence of type 2 diabetes (T2D) with sickle cell anemia calls for alternative tests. Therefore, we established a reference interval for serum fructosamine and evaluated its utility as a potential glycemic biomarker that is not affected by abnormal hemoglobin. Methods The accuracies of serum fructosamine in monitoring and diagnosing T2D were evaluated using the Area under the Receiver Operating Characteristics and other measures in 618 Nigerians with or without sickle cell trait. The estimated diagnostic cut-off for serum fructosamine was then validated in an independent multi-ethnic cohort of 634 West Africans. Results Serum fructosamine was similar between individuals with or without sickle cell trait (median: 287 vs 275 umol/L, p = 0·11, respectively) despite statistically different HbA1c. Fructosamine was highly correlated with both HbA1c and fasting glucose independently of sickle cell trait. The areas under the curve (AUC) of serum fructosamine in identifying individuals with uncontrolled glycemia and individuals with T2D were similar and independent of sickle cell trait: 0·92 (95% confidence interval [95% CI ], 0·88-0·95 and 0.92 (95% CI, (0.89–0.95) respectively. Conclusions Serum fructosamine is a good alternative to HbA1c for monitoring and diagnosing T2D in the presence of sickle cell trait.

Background Sickle cell disease (SCD) is an autosomal recessive genetic disease in which a mutation occurs in the β-globin chain gene, resulting in abnormal hemoglobin levels. In an environment with reduced oxygen concentration, red blood cells change their conformation, resulting in chronic hemolysis and consequent anemia and vaso-occlusive crises with injuries to several organs, with a significant impairment of the osteoarticular system. This study aimed to verify the chronic osteoarticular alterations and their association with clinical and laboratory characteristics of patients with SCD with a more severe phenotype (SS and Sβ0), on a steady-state fasis. Methods Fifty-five patients were referred to a medical consultation with a specialized assessment of the locomotor system, followed by laboratory tests and radiographic examinations. Results In total, 74.5% patients had hemoglobinopathy SS; 67.3% were female; and 78.2% were non-whites. The mean patient age was 30.5 years. Most patients (61.8%) reported up to three crises per year, with a predominance of high-intensity pain (65.5%). Radiographic alterations were present in 80% patients. A total of 140 lesions were identified, most which were located in the spine, femur, and shoulders. Most lesions were osteonecrosis and osteoarthritis and were statistically associated with the non-use of hydroxyurea. Conclusions There was a high prevalence of chronic osteoarticular alterations, which was statistically associated only with the non-regular use of hydroxyurea.

Purpose of review Sickle cell disease (SCD) is a hemolytic anemia caused by a point mutation in the β globin gene leading to the expression of an abnormal hemoglobin (HbS) that polymerizes under hypoxic conditions driving red cell sickling. Circulating red cells have been extensively characterized in SCD, as their destruction and removal from peripheral blood are the major contributors to anemia. However, few reports showed cellular abnormalities during erythropoiesis in SCD, suggesting that anemia could also be influenced by defects of central origin. Recent findings El Hoss et al. demonstrated ineffective erythropoiesis (IE) in SCD and deciphered the molecular mechanism underlying cell death during the hemoglobin synthesis phase of terminal differentiation. They showed that HbS polymerization induces apoptosis of differentiating erythroblasts and that fetal hemoglobin rescues these cells through its antipolymerization function. Summary IE is the major cause of anemia in β-thalassemia patients, and it is generally surmised that it contributes little to anemia of SCD. Recent reports demonstrate the occurrence of IE in SCD patients and show important alterations in the hematopoietic and erythroid niches, both in SCD patients and in the humanized Townes SCD mouse model. This implies that therapeutic strategies initially designed to improve red cell survival in the circulation of SCD patients would also positively impact erythropoiesis and bone marrow cellularity.

HemoglobinA1c (HbA1c) is used to diagnose Diabetes mellitus and monitor glycemic control over the previous eight to twelve weeks in diabetic patients. Detection of HbA1c by cation exchange-high performance liquid chromatography (CE-HPLC) gives a chromatogram by which abnormal hemoglobin variants are also picked up. Some of these may interfere with HbA1c values affecting clinical management. Due to increased inter-state migration as well as medical tourism, there is a high possibility of finding various hemoglobin variants in any part of India. We did a prospective analysis over 1.5 years, of the hemoglobin variants detected during all the HbA1c runs. The HbA1c was tested on Bio-Rad D10 dual HbA2/F/A1c platform, which uses the CE-HPLC method. Every chromatogram was carefully studied to look for unknown peaks. The samples showing unknown peaks >6% were re-run in extended HbA2/F mode to categorize the hemoglobin variants. We had 9595 HbA1c samples, of which 70 cases showed a variant window. There were 40 males and 30 females, age ranging from 28 to 76 years. The different hemoglobin variants detected were HbD, HbE and HbS in heterozygous state, high HbF (with a differential diagnosis of HPFH heterozygous and delta-beta thalassemia heterozygous), HbE homozygous, HbQ heterozygous and HbJ heterozygous. We conclude that in the process of monitoring glycemic control using HbA1c, we can also pick-up hemoglobin variants. Hence, it is essential to review HbA1c graphs, so that the diagnosis of hemoglobin variants is not missed and the HbA1c reported is reliable.