Fetal hemoglobin, blood transfusion, and retinopathy of prematurity in preterm infants: An observational, prospective study

Purpose: The objective of this study was to identify the association between fetal hemoglobin (HbF) concentration, blood transfusion, and retinopathy of prematurity (ROP) in preterm infants. Methods: This was an observational, prospective study. A total of 410 preterm infants born with <36 weeks gestational age and <2.0 kg birth weight in a tertiary care center of central India for a period of 1 year were included in this study. Clinical data were obtained from case notes. HbF of infants was measured in the blood sample using high?performance liquid chromatography at the first visit and after 1 month follow?up and was analyzed statistically. Dilated fundus examination was done as per ROP screening guidelines, and ROP was classified as per the International Classification of Retinopathy of Prematurity (ICROP), 2021. The study subjects were divided into two groups based on the status of ROP. The relationship among HbF, blood transfusion, and ROP was evaluated in both the groups. The relationship between other clinical characteristics and various neonatal risk factors was also studied between the groups. Results: A total of 410 preterm infants were included in this study, of which 110 infants had ROP (26.8%). Blood transfusion was found to be significantly associated with the development of ROP. Higher fraction of HbF (%) was associated with a lower prevalence of ROP. HbF was also inversely related with the severity of ROP. Conclusion: Replacing HbF by adult hemoglobin during blood transfusion may promote the development of ROP. Conversely, maintaining a higher percentage of HbF may be a protective factor against ROP.

Association of HMIP1 C-893A polymorphism and disease severity in patients with sickle cell anemia

Abstract Introduction: Sickle cell anemia (SCA) is a Mendelian disorder with a heterogeneous clinical course. The reasons for this phenotypic diversity are not entirely established, but it is known that high fetal hemoglobin levels lead to a milder course of the disease. Additionally, genetic variants in the intergenic region HBS1L-MYB promote high levels of fetal hemoglobin into adulthood. Objective: In the present study, we investigated the HMIP1 C-839A (rs9376092) polymorphism, located at the HBS1L-MYB intergenic region block 1, in SCA patients. Method: We analyzed 299 SCA patients followed in two reference centers in Brazil. The HMIP1 C-839A (rs9376092) genotypes were determined by allele specific polymerase chain reactions. Clinical and laboratory data were obtained from patient interviews and medical records. Results: The median fetal hemoglobin levels were higher in patients with the HMIP1 C-839A (rs9376092) AA genotype (CC = 6.4%, CA = 5.6% and AA = 8.6%), but this difference did not reach significance (p = 0.194). No association between HMIP1 C-839A (rs9376092) genotypes and other clinical and laboratorial features was detected (p > 0.05). Conclusion: In summary, our data could not support the previously related association between the HMIP1 C-893A (rs9376092) polymorphism and differential fetal hemoglobin levels.

Haematological profile of sickle cell patients attending tertiary health care centre of southern odisha: a cross sectional study

Background: Sickle Cell Disorder (SCD) is a major health problem in India. After introduction of High-Performance Liquid Chromatography (HPLC) in MKCG Medical College, this study is first of its kind to describe haemoglobin variants of SCD. The aim of the study was to document haematological profile and pattern of haemoglobin variants in SCD patients.Methods: A Hospital based cross sectional study was conducted in Pathology department, MKCG medical college from October 2018 to May 2019. Sickle cell patients were included and patients in Sickle cell crisis or transfused with blood in last 3 months were excluded. Hematological indices were measured by Sysmex XT 2000i blood analyzer. Quantification of hemoglobin variants was done by HPLC. All data were analyzed using SPSS and Independent t-test was applied.Results: In this study 100 heterozygous and 116 homozygous cases were reported. In homozygous cases Hb were significantly low and MCV, MCH, RDW-CV were significantly high than heterozygous. Hb level was significantly lower in homozygous children. Hb F was significantly higher in children and homozygous cases. A significant positive correlation was seen between Hb and RBC in both cases.Conclusions: In homozygous cases moderate anaemia (microcytic hypochromic to normocytic hypochromic) with High Hb F and in heterozygous cases mild anaemia (microcytic hypochromic) dominated the haematological profile. Children were significantly more anaemic than adults in homozygous cases. Anisocytosis was significantly more in homozygous cases and pediatric age group. Average fetal Haemoglobin variant (Hb F) was significantly more in homozygous cases and lower in adult group in both homo and heterozygous cases.

Advances in perioperative management of intrauterine blood transfusion / 中华围产医学杂志

With the fast development of fetal medicine in China,intrauterine transfusion,which is regarded as an effective treatment in certain conditions,has attracted more and more attention.In addition to the common seen red blood cell alloimmunization,the indications of intrauterine transfusion include parvovirus B 19 infection,maternal-fetal blood transfusion syndrome,twin anemia-polycythemia sequence,placental chorionic hemangiomas and fetal sacrococcygeal teratomas.The recommended approach for intrauterine transfusion is umbilical vein or intraperitoneal transfusion depending on the gestational age,placental location,and presence of absence of fetal edema.However,umbilical artery and intracardiac transfusion are not recommended.In order to reduce the complications of intrauterine transfusion,routine fetal analgesia,avoidance of umbilical artery puncture and prior use ofintrahepatic umbilical vein transfusion are recommended.Fetal middle cerebral arterypeak systolic velocity (MCA-PSV) ＞1.5 multiple of median (MOM) and 1.69 MOM can be a good indicators for the first and second intrauterine transfusions,respectively.For the third and subsequent transfusions,the rate of fetal hemoglobin decline is recommended to predict the timing of transfusion.

Fenotipificación de un caso de anemia de células falciformes / Elucidating the phenotype in a sickle cell disease case

La anemia de células falciformes es una enfermedad genética frecuente en la que la herencia de dos genes mutantes de la hemoglobina, uno de cada progenitor, produce un trastorno de la hemoglobina. Es una enfermedad crónica con exacerbaciones agudas que causan efectos a largo plazo en la educación, la vida familiar, la integración social y la calidad de vida del paciente. La clínica se resume en vaso oclusión e isquemia tisular, anemia hemolítica y la susceptibilidad a infecciones. Se presenta el caso de un hombre de raza negra, de 28 años cursando con crisis dolorosa vaso-oclusiva, trastorno hemolítico y síndrome anémico de volúmenes normales.

Sickle cell anemia is a common genetic disease in which the inheritance of two mutant hemoglobin genes, one from each parent produces a hemoglobinopathy. It is a chronic disease with acute exacerbations that cause long-term effects on education, family life, social integration and the patient's quality of life. The clinic is summarized in vaso-occlusion and tissue ischemia, hemolytic anemia and susceptibility to infections. We present the case of a 28 years old black male, suffering from a vaso-occlusive crisis, hemolytic disorder and normocytic anemic syndrome.

Prevalência de hemoglobinopatias na população adulta brasileira: Pesquisa Nacional de Saúde 2014-2015 / Prevalence of hemoglobinopathies in the Brazilian adult population: National Health Survey 2014-2015

RESUMO: Objetivo: Descrever a prevalência das hemoglobinopatias da população adulta brasileira, segundo exames laboratoriais da Pesquisa Nacional de Saúde. Métodos: Estudo descritivo realizado com os dados laboratoriais da Pesquisa Nacional de Saúde coletados entre os anos de 2014 e 2015. A pesquisa de hemoglobinopatias foi feita pelo método da cromatografia líquida de alto desempenho. Os resultados dos exames individuais foram interpretados fornecendo os parâmetros normais, homozigotos ou heterozigotos para hemoglobina S, C e D, além de outras eventuais hemoglobinopatias. Foram estimadas prevalências das hemoglobinopatias segundo sexo, cor da pele, região, idade e escolaridade. Resultados: Houve presença de hemoglobinopatias em 3,7% da população. As principais foram o traço falciforme (2,49%), a talassemia menor (0,30%) e a suspeita de talassemia maior (0,80%). Em relação ao traço falciforme e à suspeita de talassemia maior, houve diferença estatisticamente significativa para a variável cor da pele (p < 0,05). As prevalências encontradas para traço falciforme segundo cor de pele foram: preta (4,1%), parda (3,6%), branca (1,2%) e outras (1,7%). Conclusão: As hemoglobinopatias mais prevalentes foram o traço falciforme e a talassemia menor, predominando entre pretos e pardos. O estudo ajuda na identificação das hemoglobinopatias e no aconselhamento genético na preconcepção.

ABSTRACT: Objective: To describe the prevalence of hemoglobinopathies in the Brazilian adult population, according to laboratory tests from the National Health Survey. Methods: A descriptive study was carried out with National Health Survey laboratory data collected between 2014 and 2015. The hemoglobinopathies test was performed using the High Performance Liquid Chromatography method. The results of the individual tests were interpreted as providing normal, homozygous or heterozygous results for S, C and D hemoglobin, in addition to other possible hemoglobinopathies. Prevalence of hemoglobinopathies according to gender, skin color, region, age and schooling was estimated. Results: Hemoglobinopathies were present in 3.7% of the population. The main ones were the sickle cell trait (2.49%), thalassemia minor (0.30%) and suspected thalassemia major (0.80%). In relation to the sickle cell trait and suspected thalassemia major, there was a statistically significant difference for the skin color variable (p<0.05). The prevalences found for sickle cell trait according to skin color was: 4.1% among dark-skinned blacks, 3.6% among light-skinned blacks, 1.2% among whites, and 1.7% among others. Conclusion: The most prevalent hemoglobinopathies were the sickle cell trait and minor thalassemia, and were predominate among light- and dark-skinned black people. The study helps in identifying hemoglobinopathies and in genetic counseling in pre-conception.

Analysis of BCL11A gene polymorphisms and hemolysis parameters in patients with sickle-cell disease / Análise dos polimorfismos do gene BCL11A e parâmetros de hemólise em pacientes com anemia falciforme

ABSTRACT Introduction: Patients with sickle-cell disease (SCD) present chronic hemolysis with increased serum biomarkers. Genetic polymorphisms of the BLC11A gene modulate fetal hemoglobin (HbF), thus reducing hemolysis Objective: To associate the polymorphisms of BCL11A gene with the hemolysis markers: reticulocyte, bilirubin, uric acid, lactate dehydrogenase (LDH), and methemoglobin (MetHb) in SCD patients. Methods: The study included 45 patients with SCD of both sexes using hydroxyurea (HU), treated at a Hospital in Fortaleza, Ceará, Brazil, along with 80 healthy individuals as the control group. MetHb, uric acid, and bilirubin measurements were carried out with the spectrophotometric method, and LDH with a kinetic method, a reticulocyte count by a manual method; and evaluation of BCL11A polymorphisms, in real time polymerase chain reaction (PCR). Data were analyzed using the statistical software GraphPad Prism. The level of significance was set at < 5%. Results: In region rs7557939 of the BCL11A gene genotype, A/G showed a significant increase of MetHb (p = 0.0297), and the A/A genotype showed high concentration of LDH (p = 0.0316) in the same region. The use of HU at doses ≥ 10 mg/kg/day showed a decrease of LDH (p = 0.02), and treatment for > 50 months was linked to the reticulocyte count (p = 0.0155). Conclusion: Polymorphisms in the rs7557939 region of the BCL11A gene appear to somehow interfere in the clinical setting of patients with SCD, suggesting relation with the concentration of MetHb and LDH. This study pioneered an investigation into the association of hemolysis biomarkers with BCL11A gene polymorphisms in SCD.

RESUMO Introdução: Pacientes com anemia falciforme (AF) apresentam hemólise crônica com biomarcadores séricos aumentados. Os polimorfismos genéticos do gene BLC11A modulam a hemoglobina fetal (HbF), reduzindo, assim, a hemólise. Objetivo: Associar os polimorfismos do gene BCL11A aos marcadores de hemólise: reticulócitos, bilirrubina, ácido úrico, lactato desidrogenase (LDH) e meta-hemoglobina (MetHb) em pacientes com AF. Métodos: O estudo incluiu 45 pacientes com AF que utilizavam hidroxiureia (HU), tratados em um hospital de Fortaleza, Ceará, Brasil, e 80 indivíduos saudáveis como grupo-controle. A dosagem de MetHb, ácido úrico e bilirrubina foi realizada por método espectrofotométrico; LDH, pelo método cinético; contagem de reticulócitos, pelo método manual; e avaliação de polimorfismos BCL11A, por reação em cadeia da polimerase (PCR) em tempo real. Os dados foram analisados usando o software estatístico GraphPad Prism. O nível de significância foi < 5%. Resultados: Na região rs7557939 do gene BCL11A, o genótipo A/G mostrou aumento significativo de MetHb (p = 0,0297), e o genótipo A/A esteve relacionado com a alta concentração de LDH (p = 0,0316). Pacientes em uso de HU em doses ≥ 10 mg/kg/dia apresentaram diminuição de LDH (p = 0,02), e o tratamento por mais de 50 meses foi relacionado com a contagem de reticulócitos (p = 0,0155). Conclusão: Polimorfismos na região rs7557939 do gene BCL11A parecem interferir de alguma forma nas manifestações clínicas de pacientes com AF, o que sugere uma relação com a concentração de MetHb e LDH. Este estudo foi pioneiro na investigação da associação de biomarcadores de hemólise com polimorfismos do gene BCL11A na AF.

Regulatory role of microRNAs in fetal hemoglobin level / 中国病理生理杂志

MicroRNAs (miRs) play an important role in regulating diverse cellular processes.It has been reported that miRs are associated with the formation and maturation of erythrocytes, and the expression of globin genes at post-transcriptional level.Compared with normal human enrythrocytes, various miRs are altered in the patients with thalassemia.These changes also happen in the patients with diverse clinical manifestations.In this paper, we systematically summarized the recent progress about the expression dysregulation of miRs in β-thalassemia and their roles in regulating the levels of γ-globin and fetal hemoglobin.During β-like globin gene expression, miRs directly or indirectly regulate the levels of erythroid-specific transcription factors through post-transcriptional action, such as B-cell lymphoma 11A (BCL11A), myeloblastosis oncogene (MYB), specificity protein 1 (Sp1), Kruppel-like factor 3 (KLF3) and GATA1.These effects subsequently regulate the switch between γ-and β-globin gene expression and affect fetal hemoglobin production.Targeting miRs might be a novel therapeutic strategy for β-thalassmeia.

Haplotypes βs-globin and its clinical-haematological correlation in patients with sickle-cell anemia in Triângulo Mineiro, Minas Gerais, Brazil / Haplótipos da βs-globina e sua correlação clínica-hematológica em portadores de anemia falciforme no Triângulo Mineiro, Minas Gerais, Brasil

ABSTRACT Introduction: Sickle-cell anemia (SCA) is the most severe form of sickle-cell disease, and is characterized by homozygous hemoglobin S (α2βS2). Objective: Determine the haplotypes frequency in patients with SCA and their correlation with clinical and hematological profile. Method: We performed a retrospective descriptive study by reading the charts and a cross-sectional study for molecular analysis to determine the haplotypes of the gene βS globin in 61 patients with sickle-cell anemia (SS) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), using restriction endonucleases Xmn I, Hind III, Hinf I and Hinc II for analysis of six polymorphic sites in the beta cluster. Result: The genotypes were Central African Republic (CAR)/CAR (60.8%), CAR/Benin type (BEN) (13.1%), CAR/ Cameroon type (CAM) (1.6%), CAR/atypical (ATP) (13.1%), BEN/BEN (13.1%), BEN/ATP (4.9%) and ATP/ATP (3.3%). Among the analyzed chromosomes, 64.8% were CAR type, 22.1% were BEN, 12.3% ATP and 0.8% CAM. Levels of fetal hemoglobin (HbF) were significantly lower in CAR/CAR than in ATP/ATP, BEN/ATP and CAR/BEN. No association was observed between the different genotypes and clinical manifestations. Conclusion: Despite the lack of association between genotypes and clinical profiles, higher frequency of clinical events was observed in patients with at least one type of CAR chromosome. A significant association was also observed between lower average levels of HbF and CAR/CAR genotype compared to other genotypes.

RESUMO Introdução: A anemia falciforme (AF) é a forma mais grave da doença falciforme, sendo caracterizada por homozigotos de hemoglobina S (α2βS2). Objetivo: Determinar a frequência dos haplótipos de pacientes com AF e sua correlação com o perfil clínico e hematológico. Método Realizado estudo descritivo e retrospectivo, por meio da leitura dos prontuários, e estudo transversal para análise molecular a fim de determinar os haplótipos da globina do gene pS de 61 pacientes com AF (SS) por reação em cadeia da polimerase-polimorfismo de fragmentos de restrição (PCR-RFLP), utilizando endonucleases de restrição Xmn I, Hind III, Hinf I e Hinc II para análise de seis locais polimórficos no cluster beta. Resultado: Os genótipos foram Central African Republic (CAR)/CAR (50,8%), CAR/Benin type (BEN) (13,1%), CAR/Cameroon type (CAM) (1,6%), CAR/atypical (ATP) (13,1%), BEN/BEN (13,1%), BEN/ ATP (4,9%) e ATP/ATP (3,3%). Dos cromossomos analisados, 64,8% eram do tipo CAR; 22,1%, BEN; 12,3%, ATP; e 0,8%, CAM. Os níveis de hemoglobina fetal (HbF) foram significativamente menores no CAR/CAR em relação a ATP/ATP, BEN/ATP e CAR/BEN. Não houve associação entre os diferentes genótipos e as manifestações clínicas. Conclusão: Apesar da falta de associação entre genótipos e perfis clínicos, foi observada maior frequência de eventos clínicos em pacientes com pelo menos um tipo de cromossomo CAR. Observou-se também associação significativa dos níveis médios mais baixos de HbF em genótipo CAR/CAR, em comparação com outros genótipos.

Massive Fetomaternal Hemorrhage Diagnosed with High-performance Liquid Chromatography / 임상소아혈액종양

Massive fetomaternal hemorrhage (FMH) is a major cause of unexplained fetal death and neonatal anemia. FMH can be diagnosed using the Kleihauer-Betke test or flow cytometry by identifying the presence of fetal red cells in the maternal blood. However, timely diagnosis is a challenge because many hospitals lack the equipment needed to perform such tests. The authors experienced a case of FMH diagnosed via high-performance liquid chromatography (HPLC) which is generally used in measuring glycated hemoglobin (HbA1c) in a patient with unexplained neonatal anemia. A girl aged 2 days was transferred to our hospital for showing pallor and a hemoglobin level of 5.0 g/dL. HPLC revealed 3% fetal hemoglobin (HbF) in the maternal blood. HPLC is a quick test for quantifying HbF that is readily available in many hospitals and could serve as a promising alternative for diagnosing FMH.

Massive Fetomaternal Hemorrhage Diagnosed with High-performance Liquid Chromatography / 임상소아혈액종양

Massive fetomaternal hemorrhage (FMH) is a major cause of unexplained fetal death and neonatal anemia. FMH can be diagnosed using the Kleihauer-Betke test or flow cytometry by identifying the presence of fetal red cells in the maternal blood. However, timely diagnosis is a challenge because many hospitals lack the equipment needed to perform such tests. The authors experienced a case of FMH diagnosed via high-performance liquid chromatography (HPLC) which is generally used in measuring glycated hemoglobin (HbA1c) in a patient with unexplained neonatal anemia. A girl aged 2 days was transferred to our hospital for showing pallor and a hemoglobin level of 5.0 g/dL. HPLC revealed 3% fetal hemoglobin (HbF) in the maternal blood. HPLC is a quick test for quantifying HbF that is readily available in many hospitals and could serve as a promising alternative for diagnosing FMH.

Genetic variants associated with fetal hemoglobin levels show the diverse ethnic origin in Colombian patients with sickle cell anemia / Las variantes genéticas asociadas con niveles de hemoglobina fetal señalan diversos orígenes étnicos en pacientes colombianos con anemia falciforme.

Introduction: Fetal hemoglobin is an important factor in modulating the severity of sickle cell anemia. Its level in peripheral blood underlies strong genetic determination. Associated loci with increased levels of fetal hemoglobin display population-specific allele frequencies. Objective: We investigated the presence and effect of known common genetic variants promoting fetal hemoglobin persistence (rs11886868, rs9399137, rs4895441, and rs7482144) in 60 Colombian patients with sickle cell anemia. Materials and methods: Four single nucleotide polymorphisms (SNP) were genotyped by restriction fragment length polymorphisms (RFLP) and the use of the TaqMan procedure. Fetal hemoglobin (HbF) from these patients was quantified using the oxyhemoglobin alkaline denaturation technique. Genotype frequencies were compared with frequencies reported in global reference populations. Results: We detected genetic variants in the four SNPs, reported to be associated with higher HbF levels for all four SNPs in the Colombian patients. Genetic association between SNPs and HbF levels did not reach statistical significance. The frequency of these variants reflected the specific ethnic make-up of our patient population: A high prevalence of rs7482144-'A' reflects the West-African origin of the sickle cell mutation, while high frequencies of rs4895441-'G' and rs11886868-'C' point to a significant influence of an Amerindian ethnic background in the Colombian sickle cell disease population. Conclusion: These results showed that in the sickle cell disease population in Colombia there is not a unique genetic background, but two (African and Amerindian). This unique genetic situation will provide opportunities for a further study of these loci, such as fine-mapping and molecular-biological investigation. Colombian patients are expected to yield a distinctive insight into the effect of modifier loci in sickle cell disease.

Introducción. La hemoglobina fetal es un importante factor modulador de la gravedad de la anemia falciforme, cuya expresión está muy condicionada por el factor genético. Los loci asociados con el incremento de la hemoglobina fetal pueden presentar frecuencias alélicas específicas para cada población. Objetivo. Investigar la presencia y el efecto de las variantes genéticas rs11886868, rs9399137, rs4895441 y rs7482144 asociadas con la persistencia de hemoglobina fetal, en 60 pacientes colombianos con anemia falciforme. Materiales y métodos. Se hizo la genotipificación de los polimorfismos de nucleótido simple ( Single Nucleotide Polymorphisms, SNP) mediante la técnica de polimorfismos de longitud de fragmentos de restricción ( Restriction Fragment Length Polymorphisms, RFLP) y el procedimiento TaqMan. La hemoglobina fetal (HbF) se cuantificó utilizando la técnica de desnaturalización alcalina de la oxihemoglobina. Las frecuencias genotípicas se compararon con las reportadas en poblaciones de referencia global. Resultados. Se observaron variantes genéticas ya reportadas para aumento de HbF en los cuatro SNP. La asociación genética entre los SNP y el incremento de la HbF no alcanzó significancia estadística. La frecuencia de estos alelos reflejó la siguiente composición específica en esta muestra de pacientes colombianos: una gran prevalencia de rs7482144-'A', lo que indica que el origen de la mutación para la anemia falciforme es África occidental, y una gran frecuencia de rs4895441-'G' y rs11886868-'C', lo que denota la influencia significativa del origen genético amerindio. Conclusión. Los resultados evidenciaron que la población con anemia falciforme de Colombia no tiene un único origen genético, sino que existen dos (africano y amerindio). Esta situación genética única ofrece la oportunidad de llevar a cabo un estudio más amplio de estos loci a nivel molecular. Se espera que el estudio de pacientes colombianos permita una visión diferente del efecto de los loci modificadores en esta enfermedad.

Hemoglobina en recién nacidos por parto vaginal según clampaje precoz o tardío del cordón umbilical, a 2 700 metros sobre el nivel del mar

Diversos estudios han demostrado que un clampaje tardío del cordón umbilical aumenta los niveles de hemoglobina de los recién nacidos. Objetivos: Evaluar si el clampaje tardío del cordón umbilical en neonatos a término muestra mayores valores de hemoglobina que cuando se realiza clampaje precoz, a 2700 msnm. Diseño: Investigación prospectiva, aleatorizada y doble ciego. Institución: Departamento de GinecoObstetricia, Hospital Regional de Cajamarca, Perú. Participantes: Recién nacidos y sus madres. Métodos: En enero de 2014, a 100 gestantes en trabajo de parto con gestación única, a término y sin otros factores de riesgo, se asignó al azar clampaje tardío (cuando dejó de latir el cordón umbilical 1 a 3 minutos) o clampaje precoz (alrededor de 10 segundos después del parto). Se midió el tiempo desde que aparecieron los hombros del bebé. Se procedió a sacar una muestra de sangre del talón derecho del recién nacido en 2 capilares y a las 6 horas de vida, y se analizó la hemoglobina, el hematocrito y grupo y factor Rh. Principales medidas de resultados: Nivel de hemoglobina. Resultados: Encontramos 91 % de gestantes sin anemia y 9% con anemia; el grupo sanguíneo materno predominante fue el O+ en 86%. Se practicó clampaje tardío a 52 recién nacidos y clampaje precoz a 48. El 94% de los recién nacidos pesó entre 2 501 Y 3 999 g, con Ápgar > 7 en el 100%. El tiempo en que dejó de latir el cordón umbilical fue 2,67+-0,28 minutos. En 100% de los neonatos con clampaje temprano el valor de la hemoglobina fue <15 mg/dLy en el clampaje tardío el 71,1 % presentó hemoglobina de 15,1 a 20,1 mg/dL, y 28,9% más de 20,1 mg/dL. No hubo diferencia significativa en los valores de hemoglobina de los recién nacidos sí la madre presentó o no anemia. Conclusiones: El clampaje tardío mostró mejores valores de hemoglobina en los neonatos. El tiempo medio en que dejó de latir el cordón fue 2,67 min y la anemia materna no influyó en la hemoglobina neonatal.

Several studies have shown that late cord clamping in creases levels of hemoglobin in newborns. Objectives: To determine whether delayed umbilical cord clamping in term infants show higher hemoglobin levels than early clamping, investigation performed at 2700 m.a.s.l. Design: Prospective, randomized, double blind study. Setting: Gynecology and Obstetrics Department, Hospital Regional de Cajarnarca, Peru. Participants: Newborns and their moth­ ers. Methods: In january 2014, 100 pregnant women in labor with singleton pregnancies at term and without other risk factors were randomized to delayed clamping (when the umbilical cord stopped beats in 1-3 minutes) or early clamping (about 1 O seconds after birth). Time was measured starting when baby shoulders appeared. A blood sample from the right newborn's heel was obtained and placed in 2 capillaries, at birth and also at 6 hours of life; hemoglobin, hematocrit, and group and Rh factor were analyzed. Main outcome measures: Hemoglobin levels. Results: Ninety-one per cent of pregnant women did not have anemia and 9% had anemia; maternal blood group was 0+ in 86%; 94% of newborns weighed 2 501-3 999 g, Apgar >7 was found in all newborns. Late clamping was done in 52 infants and early clamping in 48. The umbilical cord stopped beating at 2.67+-0.28 minutes. In 100% of infants with early clamping hemoglobin value was <15 mg/dL, and in late clamping 71.1 % had hemoglobin 15.1­ 20.1 mg/dL and 28.9% over 20.1 mg/dL. There was no significant difference in newborn hemoglobin values whether the mother presented anemia or not. Conclusions: Late clamping resulted in better neonatal hemoglobin values. Average time for the umbilical cord stopping beats was 2.67 mino Maternal anemia did not affect neonatal hemoglobin at 2 700 m.a.s.l.

Pattern of hemolysis parameters and association with fetal hemoglobin in sickle cell anemia patients in steady state

This study aimed to evaluate the influence of fetal hemoglobin (Hb F) on hemolysis biomarkers in sickle cell anemia patients. Methods: Fifty adult sickle cell anemia patients were included in the study. All patients were taking hydroxyurea for at least six months and were followed at the outpatient clinic of a hospital in Fortaleza, Ceará, Brazil. The control group consisted of 20 hemoglobin AA individuals. The reticulocyte count was performed by an automated methodology, lactate dehydrogenase and uric acid were measured by spectrophotometry and arginase I by enzyme-linked immunosorbent assay (ELISA). The presence of Hb S was detected by high-performance liquid chromatography. The level of significance was set for a p-value <0.05. Results: A significant increase was observed in the reticulocyte count and lactate dehydrogenase, uric acid and arginase I levels in sickle cell anemia patients compared to the control group (p-value <0.05). Patients having Hb F levels greater than 10% showed a significant decrease in the reticulocyte count, arginase I and lactate dehydrogenase. A significant decrease was observed in arginase I levels in patients taking hydroxyurea at a dose greater than 20 mg/kg/day. Conclusion: The results of this study show that sickle cell anemia patients have increases in the hemolysis biomarkers, lactate dehydrogenase, reticulocyte count, arginase I, uric acid and increases in Hb F can reduce the reticulocyte count and arginase I and lactate dehydrogenase levels.

The study on fetal hemoglobin in improving anemia of β-thalassemia carriers / 国际检验医学杂志

Objective To investigate the effect of fetal hemoglobin( HbF) in improving anemia of women who were β‐thalasse‐mia carriers at childbearing age .Methods 289 cases of women at childbearing age diagnosed as β‐thalassemia carriers in Shenzhen City were enrolled in this study .The high performance liquid chromatography (HPLC) was uesed for quantitative analysis of HbF , and the red blood cell parameters were detected by using the LH750 Automatic blood cell analyzer .The differences of red blood cell parameters between the HbF normal group and the HbF increased group were compared ,and the relationship between the high HbF expression rates and gene mutations were also analyzed .Results Comapred with the HbF normal group ,the hemoglobin (HGB) levels ,mean corpuscular volume (MCV) and the mean corpuscular hemoglobin (MCH) increased significantly ,while the red blood cell (RBC) count reduced ,there were significant differences between the two groups (P0 .05) .There were no significant differnces of rates of HBF high expression between different types of β‐globin gene mutations and the overall rate of HBF high expression (P>0 .05) .Conclusion Compared with the HbF normal group , anemia may improve more significantly in cases of women diagnosed as β‐thalassemia carriers at childbearing age in the HbF in‐creased group ,and there may be no relationship between gene mutations and high expression of HbF .

Análisis de pacientes drepanocíticos tratados con hidroxiurea en el Hospital Nacional de Niños / Evaluation of sickle cell patients treated with hidroxyurea at the National Children's Hospital

Antecedentes: desde 1984 estudios comprobaron que la hidroxiurea aumentaba los niveles de hemoglobina fetal y del volumen corpuscular medio, por esta razón a partir de 1998 fue el primer fármaco aprobado para el tratamiento en la drepanocitosis. El objetivo de este estudio fue describir la respuesta y complicaciones de los pacientes drepanocíticos en tratamiento con hidroxiurea en el Hospital Nacional de Niños. Métodos: estudio transversal y retrospectivo, realizado en pacientes con drenopacitosis atendidos en el servicio de Hematología del Hospital Nacional de Niños de enero 2006 a diciembre 2009; se incluyeron pacientes cuyo expediente clínico reunía los criterios de inclusión...

Clinical and hematological effects of hydroxyurea therapy in sickle cell patients: a single-center experience in Brazil / Efeitos clinicos e hematologicos do tratamento com hidroxiureia em pacientes falciformes: experiencia de um centro no Brasil

CONTEXT AND OBJECTIVES Sickle cell disease (SCD) is the most common genetic disorder among people of African descent, affecting approximately 3,500 newborns each year in Brazil. Hydroxyurea (HU) is the only effective drug to treating patients with SCD, thereby reducing morbidity and mortality. The objective was to analyze the effects of HU on SCD patients at our institution. DESIGN AND SETTING Retrospective study conducted at a sickle cell centre in Ribeirão Preto, São Paulo, Brazil. METHODS We analyzed clinical and laboratory data on 37 patients. The hematological parameters and clinical events that occurred during the year before and the first year of treatment with HU were analyzed. The mean dose of HU was 24.5 ± 5.5 mg/kg/day. RESULTS There were rises in three parameters: hemoglobin (8.3 g/dl to 9.0 g/dl, P = 0.0003), fetal hemoglobin (HbF) (2.6% to 19.8%, P < 0.0001) and mean cell volume MCV (89 to 105 fl, P = 0.001); and reductions in the numbers of leukocytes (10,050/µl to 5,700/µl, P < 0.0001), neutrophils (6,200/µl to 3,400/µl, P = 0.001), platelets (459,000/µl to 373,000/µl, P = 0.0002), painful crises (1.86 to 0.81, P = 0.0014), acute chest syndromes (0.35 to 0.08, P = 0.0045), infections (1.03 to 0.5, P = 0.047), hospitalizations (1.63 to 0.53, P = 0.0013) and transfusions (1.23 to 0.1, P = 0.0051). CONCLUSION The patients presented clinical and hematological improvements, with an increase in HbF and a reduction in the infection rate, which had not been addressed in most previous studies. .

CONTEXTO E OBJETIVO A doença falciforme (SCD) é o distúrbio genético mais comum entre afrodes-cendentes, afetando aproximadamente 3.500 recém-nascidos a cada ano no Brasil. A hidroxiureia (HU) é a única droga efetiva para o tratamento dos pacientes com SCD, reduzindo a morbidade e a mortalidade da doença. O objetivo do estudo foi analisar os efeitos da HU em pacientes com SCD em nossa instituição. TIPO DE ESTUDO E LOCAL Estudo retrospectivo realizado em um centro de anemia falciforme em Ribeirão Preto, São Paulo, Brasil. MÉTODOS Nós analisamos os dados clínicos e laboratoriais de 37 pacientes. Os parâmetros hematológicos e eventos clínicos que ocorreram no ano anterior e durante o primeiro ano de tratamento com HU foram analisados. A dose média de HU foi 24.5 ± 5.5 mg/kg/dia. RESULTADOS Houve aumento em três parâmetros estudados: hemoglobina (8,3 g/dl para 9,0 g/dl, P = 0,0003), hemoglobina fetal (HbF) (2,6% para 19,8%, P < 0,0001) e volume corpuscular médio (VCM) (89 para 105 fl, P = 0,001); e redução do número de leucócitos (10.050/µl para 5.700/µl, P < 0,0001), neutrófilos (6.200/µl para 3.400/µl, P = 0,001), plaquetas (459.000/µl para 373.000/µl, P = 0,0002), crises dolorosas (1,86 para 0,81, P = 0,0014), síndrome torácica aguda (0,35 para 0,08, P = 0,0045), infecções (1,03 para 0,5, P = 0,047), hospitalizações (1,63 para 0,53, P = 0,0013) e número de transfusões (1,23 para 0,1, P = 0,0051). CONCLUSÃO Os pacientes apresentaram melhora clínica e hematológica, com aumento da HbF e redução da taxa de infecção, dado este não explorado na maioria dos estudos clínicos já publicados. .

Genetic study of a case with abnormal hemoglobin Ta-li combined with hereditary persistence of fetal hemoglobin / 中华检验医学杂志

ObjectiveTo investigate the genotype of a case with abnormal hemoglobin combined with hereditary persistence of fetal hemoglobin (HPFH).Methods Male patient,26 years old,were suspected abnormal hemoglobin combined with HPFH after receiving medical examination including hematology exmination,hemoglobin electrophoresis,erythrocyte osmotic fragility analysis in Guangzhou Kingmed Diagnostics in September 2010.Routine examination of anemia and hemoglobin electrophoresis at alkaine pH on agarose gels were applied to analyze the phenotype.Direct sequencing of the complete HBB gene was utilized to identify the hemoglobin variant.Multiplex ligation-dependent probe amplification (MLPA) assay was used to identify the presence of β-globin gene cluster deletion.Gap polymerase chain reaction (gap-PCR) was used to amplify the HBB gene fragment across the breakpoint,and the deletion breakpoint was characterized by direct sequencing the gap-PCR product and comparing the sequencing result with the reference sequence NC_000011.9.ResultsBy direct sequencing of the complete HBB gene,the patient in this study was found to carry a hemoglobin Ta-Li (HBB:c.250G ＞ T) mutation.By combining use of MLPA and gap-PCR with gene sequencing,we found that it had a gross deletion in the β-globin gene cluster,the deletion region was NC_000011.9:g.5222878_5250288del.Therefore,the genotype of this subject was SEA-HPFH combined with abnormal hemoglobin Ta-li.ConclusionCombining application of MLPA and gap-PCR with gene sequencing can help to make sure the genotype.

What influences Hb fetal production in adulthood?: [review]

Human hemoglobin genes are located in α and β globin gene clusters in chromosomes 16 and 11, respectively. Different types of hemoglobin are synthesized according to the stage of development with fetal hemoglobin (α2γ2) (Hb F) being the main hemoglobin in the fetal period. After birth, there is a reduction (to about 1 percent) in Hb F levels and adult hemoglobin, Hb A (2α2β2), increases to more than 96 percent of total hemoglobin. However, some genetic conditions whether linked to the β-globin gene cluster or not are associated with high Hb F levels in adults. Among those linked to β-globin are hereditary persistence of fetal hemoglobin, delta-beta thalassemia (δβ-Thalassemia) and the XmnI polymorphism (-158 C > T). Other polymorphisms not related to β-globin gene cluster are known to influence the γ-globin gene expression in adulthood. The most relevant polymorphisms that increase concentrations of Hb F are the HMIP locus on chromosome 6, the BCL11A locus on chromosome 2, the Xp22.2 region of the X chromosome and the 8q region on chromosome 8. Findings from our research group studying genetic factors involved in γ-globin gene regulation in adults without anemia in the northwestern region of São Paulo State showed that high Hb F levels are influenced by the presence of hereditary persistence of fetal hemoglobin mutations and the XmnI polymorphism, suggesting that both genetic alterations characterize the molecular basis of the evaluated population.

Patients with sickle cell disease taking hydroxyurea in the Hemocentro Regional de Montes Claros

BACKGROUND: The development of therapies for sickle cell disease has received special attention, particularly those that reduce the polymerization of hemoglobin S. Hydroxyurea is a commonly used medication because it has the ability to raise levels of fetal hemoglobin, decrease the frequency of vaso-occlusive episodes and thus improve the clinical course of sickle cell disease patients. OBJECTIVE: To study hematological data and the clinical profile of sickle cell disease patients taking hydroxyurea in a regional blood center. METHODS: From the charts of 20 patients with sickle cell anemia, the clinical outcomes and a number of hematological variables were analyzed before and during treatment with hydroxyurea. RESULTS: The patients' ages ranged from 6 to 41 years old, most were dark skinned and there was a predominance of women. The main symptom that defined whether patients were prescribed hydroxyurea was painful crises followed by hospitalizations. During treatment with hydroxyurea there were significant increases in hemoglobin, fetal hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin. The reticulocyte and white blood cell counts dropped significantly with treatment. A positive correlation was found between fetal hemoglobin and mean corpuscular volume before and during treatment. Additionally, a correlation was found between the white blood cell and reticulocyte counts before treatment with hydroxyurea. CONCLUSION: Most patients showed improvements with treatment as demonstrated by increases in hemoglobin, fetal hemoglobin and mean corpuscular volume, as well as by reductions in the reticulocyte and white blood cell counts. Clinically, more than 50 percent of patients had a significant reduction of events.