Clinical, laboratory, and molecular characteristics of a cohort of children with hemoglobinopathy S/betathalassemia

ABSTRACT Introduction: Hemoglobinopathy Sβ-thalassemia (HbSβ-thal) has a wide range of clinical and laboratory severity. There is limited information on the natural history of HbSβ-thal and its modulating factors. We described the molecular, hematological, and clinical characteristics of a cohort of children with HbSβ-thal and estimated its incidence in Minas Gerais, Brazil. Methods: Laboratory and clinical data were retrieved from medical records. Molecular analysis was performed by HBB gene sequencing, PCR-RFLP, gap-PCR, and MLPA. Results: Eighty-nine children were included in the study. Fourteen alleles of β-thal mutations were identified. The incidence of HbSβ-thal in the state was 1 per 22,250 newborns. The most common βS-haplotypes were CAR and Benin. The most frequent βthal-haplotypes were V, II, and I. Coexistence of 3.7 kb HBA1/HBA2 deletion was present in 21.3 % of children. β-thalassemia mutations were associated with several clinical and laboratory features. In general, the incidence of clinical events per 100 patient-years was similar for children with HbSβ0-thal, IVS-I-5 G>A, and IVS-I-110 G>A. Children with HbSβ+-intermediate phenotypes had a more severe laboratory and clinical profile when compared with those with HbSβ+-mild ones. βS-haplotypes and α-thalassemia did not meaningfully influence the phenotype of children with HbSβ-thal. Conclusion: The early identification of b-thalassemia alleles may help the clinical management of these children. © 2023 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license

MTHFR C677T Polymorphism, Plasma Homocysteine, and PDGF-AA Levels and Transcranial Doppler Velocity in Children With Sickle Cell Disease

Objective: To evaluate the effect of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on plasma homocysteine (tHcy) and platelet-derived growth factor (PDGF-AA) levels in children with sickle cell disease (SCD), and ascertain their role in predicting high transcranial doppler velocity (TCD). Methods: We estimated MTHFRC677T gene polymorphism, plasma tHyc and PDGF-AA in 44 SCD patients and 44 healthy children. Results: The prevalence of mutant homozygous MTHFR (C677TT) in SCD was 13.6%. Significantly higher plasma tHcy was observed in mutant homozygous MTHFRC677TT patients. Significantly higher plasma tHcy and PDGF-AA levels were observed in SCD patients than in controls. Median (IQR) PDGF-AA levels were significantly higher in conditional and high-risk TCD patients as compared to low-riskTCD patients [325 (93.1-368) and 368 (111-480) vs 111 (56-201) pg/mL, respectively; P<0.001]. Mean (SD) tHcy levels were significantly higher in high-risk TCD children than low-risk TCD children (12.9 (2.7) vs 9.9 (2.5) µmol/L; P=0.006). The receiver operating characteristic revealed that the area under the curve (AUC) of PDGF-AA for high TCD velocity was 0.934 (95% CI 0.845-1.00; P<0.001) and tHcy had an AUC of 0.675 (95% CI 0.517-0.833; P=0.04). Conclusion: PDGF-AA and tHcy levels could be used as predictive markers for stroke in SCD children. MTHFR Polymorphism contributes to elevated tHcy levels.

Sickle cell anemia: hierarchical cluster analysis and clinical profile in a cohort in Brazil

Abstract Introduction Sickle cell anemia is a monogenic disorder caused by a mutation in the β-hemoglobin gene, resulting in sickle hemoglobin that can polymerize. Presentation and clinical course have significant inter-individual variability and classifying these patients for severity is a challenge. Methods We applied hierarchical clusters with 10 routine laboratory tests to understand if this grouping could be associated with clinical manifestations. We included 145 adult homozygous patients (SS) at an outpatient clinic in a retrospective study. Results We found five clusters by counting those that had been differentiated by unconjugated bilirubin, reticulocytes, LDH, leukocytes, lymphocytes and monocytes. When comparing groups to clinical findings, the clusters were different only for liver abnormality. Cluster 3 had the lower median of reticulocytes, LDH, leukocytes, lymphocytes and monocytes and a higher percentage of patients under treatment. Clusters 4 and 5 had higher frequencies of liver impairment and higher medians of reticulocytes, LDH, leukocytes, lymphocytes and monocytes. Hemolysis and inflammation seemed to influence the grouping. Conclusion In our study, cluster analysis showed five groups that exhibited different degrees of inflammation and hemolysis. When comparing clinical data, the result was different only for the criteria of liver abnormality.

Ácido úrico en las gestantes con diagnóstico de drepanocitosis y preeclampsia / Uric acid in pregnant women diagnosed with sickle cell disease and preeclampsia

RESUMEN Introducción: El ácido úrico es el producto final del ciclo de las purinas y es fundamental como marcador de enfermedad renal, la gota y la preeclampsia. Este biomarcador ejerce efectos potenciales en la placenta y el feto de la gestante con drepanocitosis. Objetivo: Describir los efectos potenciales que produce el ácido úrico en las gestantes con drepanocitosis. Métodos: Se revisó literatura en inglés y en español, a través del sitio web PubMed y el motor de búsqueda Google académico, en artículos publicados en los últimos cinco años. Se utilizaron como términos de búsqueda: preeclampsia, ácido úrico y riesgos en las embarazadas con drepanocitosis. Se analizaron los aspectos más relevantes del tema en la bibliografía revisada. Análisis y síntesis de la información: El incremento del ácido úrico añadido a la vasoclusión, la hipoxia y la necrosis tisular a nivel de la placenta son mecanismos invocados en el desarrollo de la preeclampsia y los índices de partos prematuros que presentan. Es de destacar que no tiene una trayectoria uniforme en todas las pacientes, sobre todo se observa una mejor evolución (con menor presencia de estas complicaciones) en aquellas pacientes que muestran genotipo, niveles de hemoglobina fetal y haplotipo de la hemoglobina S más favorable. Conclusiones: El ácido úrico constituye un biomarcador útil y de alarma en el diagnóstico de la preeclampsia, una de las peores complicaciones tanto para la vida materna como para su descendencia, al ser la gestante con drepanocitosis una paciente de muy alto riesgo de parto pretérmino, prematuridad, bajo peso al nacer, nacidos muertos e infarto placentario.

ABSTRACT Introduction: Uric acid is the end product of the purine cycle and is essential as a marker of kidney disease, gout and pre-eclampsia. This biomarker has potential effects on the placenta and fetus of a pregnant woman with sickle cell disease. Objective: To describe the potential effects of uric acid in pregnant women with sickle cell disease. Methods: Literature in English and Spanish was reviewed, through the PubMed website and the academic search engine Google, in articles published in the last five years. The search terms were: pre-eclampsia, uric acid and risks in pregnant women with sickle cell disease. The most relevant aspects of the subject were analyzed in the reviewed bibliography. Analysis and synthesis of information: The increase in uric acid added to vasoocclusion, hypoxia and tissue necrosis at the level of the placenta are mechanisms invoked in the development of pre-eclampsia and the rates of premature births they present. It is noteworthy that it does not have a uniform trajectory in all patients, especially a better evolution is observed, with less presence of these complications in those patients who show a more favorable genotype, fetal hemoglobin levels and hemoglobin S haplotype. Conclusions: Uric acid constitutes a useful and alarm biomarker in the diagnosis of pre-eclampsia, one of the worst complications both for maternal life and for her offspring, as the pregnant woman with sickle cell disease is a patient at a very high risk of preterm delivery. prematurity, low birth weight, stillbirths and placental infarction.

Morbilidad y mortalidad de 599 pacientes con drepanocitosis en el Instituto de Hematología e Inmunología / Morbidity and mortality of 599 sickle cell disease patients in the Institute of Hematology and Immunology

Introducción: La drepanocitosis es la anemia hemolítica congénita más común del mundo. Entre el 5 y 15 por ciento de la población mundial es portadora de la hemoglobina S y en Cuba, la frecuencia es de 3,08 por ciento, lo que representa un problema de salud pública. Objetivo: Caracterizar el cuadro clínico, el perfil hematológico y la probabilidad de supervivencia de los pacientes con drepanocitosis en el Instituto de Hematología e Inmunología. Método: Se realizó estudio descriptivo, longitudinal y retrospectivo, que incluyó todos los enfermos seguidos, al menos dos años, en la institución, entre enero de 1973 y diciembre del 2009. Resultados: Se incluyeron 599 pacientes (285 masculinos), 439 SS/Sβ0tal y 160 SC/Sβ+tal. El seguimiento medio fue de 17,6±9,5 años. Predominaron los pacientes entre 20 y 59 años. Los eventos clínicos más frecuentes fueron las crisis vasoclusivas dolorosas, las infecciones, el síndrome torácico agudo y las complicaciones hepáticas. Los valores de reticulocitos, plaquetas, leucocitos y hemoglobina fetal fueron significativamente mayores en los pacientes SS/Sβ0tal; no así la hemoglobina total que fue mayor en los SC/Sβ+tal. La probabilidad de supervivencia global de los pacientes a los 45 años fue de 69 por ciento. Los accidentes vasculares encefálicos (17,5 por ciento), las complicaciones hepáticas (17,5 por ciento) y las cardíacas (14,28 por ciento) fueron las principales causas de muerte. Conclusiones: La distribución demográfica y por hemoglobinopatías, el cuadro clínico, y el perfil hematológico fueron similares a los encontrados en pacientes de otras regiones geográficas, excepto la frecuencia de complicaciones hepáticas que fue mayor. La probabilidad de supervivencia fue similar con los mejores centros de atención en el mundo(AU)

Introduction: Sickle cell disease is the most common congenital hemolytic anemia in the world. Between 5 to 15 percent of the world population is a carrier of hemoglobin S and in Cuba, the frequency is 3.08 percent, which represents a public health problem. Objective: To characterize the clinical picture, the hematological profile, and the probability of survival of patients with sickle cell disease at the Institute of Hematology and Immunology. Method: A descriptive, longitudinal and retrospective study was carried out, which included all patients followed up for at least two years at the institution between January 1973 and December 2009. Results: 599 patients (285 male), 439 SS/Sβ0tal and 160 SC/Sβ+tal, were included. The mean follow-up was 17.6±9.5 years. Patients between 20 and 59 years old predominated. The most frequent clinical events were painful vasocclusive crises, infections, acute chest syndrome, and liver complications. The reticulocytes, platelets, leukocytes and fetal hemoglobin values ​​were significantly higher in the SS/Sβ0tal patients, but not the total hemoglobin, which was higher in the SC/Sβ+tal. The overall survival probability of patients at 45 years was 70 percent. Stroke (17.5 percent), liver complications (17.5 percent), and cardiac complications (14.28 percent) were the main causes of death. Conclusions: The demographic distribution and by hemoglobinopathies, the clinical events, and the hematological profile were similar to those found in patients from other geographic regions, except the frequency of liver complications, which was higher. The probability of survival was comparable with the best care centers in the world(AU)

Análise do perfil de doadores de sangue positivos para hemoglobina S em hemocentro do estado do Rio Grande do Sul / Profile assessment of blood donors with sickle cell trait in a public blood bank in Southern Brazil

Introdução: Portadores do traço falciforme podem doar sangue, porém requerem maior atenção ao direcionamento da sua transfusão. Considerando o perfil étnico- racial da região sul do Brasil, o presente artigo teve como objetivo analisar o perfil e a prevalência de Hemoglobina S em um hemocentro público de Porto Alegre. Métodos: Estudo transversal retrospectivo realizado através de uma pesquisa em banco de dados cadastrais e de resultados de testes imunológicos no período de janeiro de 2015 a dezembro de 2019. Resultados: Foram obtidos um total de 8.2363 registros cadastrais e 6.7184 testes imunológicos. Dos testes, 467 foram positivos para Hemoglobina S de 134 doadores distintos. O percentual de Hb S positiva apresentou uma média de 0,7% anual entre todos os doadores. Entre doadores autodeclarados "Negros" a prevalência é de 0,92% e "Caucasianos" é de 0,13%. Conclusão: Os dados corroboram com a literatura, porém o espectro social que abrange as denominações "Caucasiano Brasileiro" e "Mestiço" permanecem em questionamento dentro da relevância do marcador étnico da Hemoglobina S no Rio Grande do Sul. (AU)

Introduction: People with sickle cell trait can donate blood, but special attention should be paid to the transfusion recipient. Considering the ethnic-racial profile of Southern Brazil, this article aimed to analyze the profile and prevalence of hemoglobin S in a public blood bank in Porto Alegre. Methods: A quantitative, retrospective, and cross-sectional study was conducted to assess the profile of blood donors positively screened for hemoglobin S from January 2015 to December 2019 in a public blood bank in Southern Brazil. Results: A total of 82,363 records and 67,184 immunohematological tests were obtained. Regarding the tests, 467 were positive for hemoglobin S among 134 different donors. The percentage of positive hemoglobin S has remained stable over the years, with an annual average of 0.7%. The prevalence of self-reported "black" and "Brazilian Caucasian" blood donors was 0.92% and 0.13%, respectively. Conclusions: The data are in accordance with the literature; however, the social spectrum that comprises the terms "Brazilian Caucasian" and "mixed-race" remains in question regarding the relevance of the ethnic marker of hemoglobin S in Southern Brazil. (AU)

Condições clínicas, nutricionais e sociais de crianças com doença falciforme acompanhadas em um centro de referência: estudo descritivo / Clinical, nutitional and family conditions of children with sickle cell disease followed up in a referral hematology center: a descriptive study

Objetivo: Descrever as características clínicas, sociais e nutricionais de crianças com doença falciforme de 5-9 anos. Método: Trata-se de estudo seccional em amostra aleatória de 190 crianças avaliada entre 2015 e 2016, cadastradas em um hospital de referência em hematologia do Rio de Janeiro, Brasil. Resultados: A maioria das crianças estudadas possuía o genótipo Hb SS (65,3%), teve seu diagnóstico na triagem neonatal (91%) e iniciou o acompanhamento médico antes dos seis meses de idade (91,5%). Excesso de peso e baixa estatura foram encontrados em 14,2% e 6,2% das crianças, respectivamente. Em relação às condições sociais da família, a maioria dos pais possuíam companheiros (60,5%), viviam com até meio salário mínimo (55,8%) e as mulheres deixaram seus empregos para acompanhar o tratamento da criança (52,4%). Conclusão: As crianças com doença falciforme foram diagnosticadas precocemente, aproximadamente um sexto delas estavam em excesso de peso e 20% declararam renda de até um quarto de salário mínimo. O fortalecimento da rede de atenção no SUS às pessoas com DF é uma importante medida para mitigar os problemas identificados neste estudo. (AU)

Objective: To describe the clinical, social and nutritional characteristics of children with sickle cell disease aged 5 to 9 years. Method: Cross-sectional study carried out in 2015- 2016 with a random sample of 190 children receiving care at a reference hematology hospital in Rio de Janeiro, Brazil. Results: The majority of the children had the genotype Hb SS (65.3%), were diagnosed with SCD during newborn screening (91%) and began clinical treatment before six months of age (91.5%). Overweight and low stature were found in 4.2% and 6.2% of the children, respectively. With respect to the household socioeconomic conditions, most of the parents had a partner (60.5%), lived with up to half the minimum wage (55.8%), and the women quitted their jobs to take care of their children (52.4%). Conclusion: Children with sickle cell disease were diagnosed early; nearly one sixth of them were overweight; and 20% of the parents had income of up to one fourth of the minimum wage. Strengthening the health care network in SUS for individuals with SCD is of vital importance to mitigate the problems identified in this study. (AU)

Herencia conjunta de α+-talasemia y portador de hemoglobina S / Co-inheritance of α+-thalassemia and sickle trait

Resumen En este reporte de caso se describe el primer paciente doble heterocigoto para alfa+-talasemia tipo -3,7 y rasgo heterocigoto por hemoglobina S en Costa Rica, diagnosticado desde su nacimiento por medio del tamizaje neonatal como heterocigoto para hemoglobina S. Luego de la detección de la hemoglobina S por tamizaje, el paciente fue referido al servicio de Hematología del Hospital Nacional de Niños para su seguimiento, en donde se observa hemograma con índices y morfología de glóbulos rojos sugestivos de alfa talasemia, con presentación de electroforesis de hemoglobina con patrón AS cuya expresión relativa de HbS era menor de lo esperado, lo que motivó a efectuar estudio molecular del gen de alfa globina, que confirmó el diagnóstico de alfa talasemia con deleción heterocigota de tipo -3,7 en herencia conjunta con la heterocigosis de hemoglobina S.

Abstract In this case report we describe the first patient compound heterozygous for type -3.7 alpha+ thalassemia and sickle cell trait in Costa Rica, who was diagnosed from birth by neonatal screening as heterozygous for hemoglobin S. After detection of hemoglobin S by screening, the patient was referred to the Hematology service of the National Children`s Hospital for follow-up, where hemogram with indexes and morphology of red blood cells suggestive of alpha thalassemia is observed, presenting hemoglobin electrophoresis with AS pattern whose relative expression of hemoglobin S was lower tan expected, which led to a molecular study of the alpha globin gene confirming the diagnosis of alpha thalassemia with heretozygous deletion of type -3.7, in co-inheritance with hemoglobin S heterozygosis.

Evolutionary profile of patients with hemoglobin SC disease regularly followed in Côte d'Ivoire

Background: West Africa is recognized as the elective focus of hemoglobin C. The S and C combination in the same patient gives a major sickle cell syndrome. In our country, very few series dealing with the evolutionary features of this SC form have been published contrary to the homozygous SS form. The aim of this study was to describe the evolutionary profile of double heterozygous SC sickle cell patients.Methods: This was a retrospective and prospective study with descriptive and analytical purpose of 174 SC sickle cell patients.Results: The median age was 26 years with extremes of 6 years and 57 years. 96% of patients had less than 4 vaso-occlusive seizures per year. The evolutionary complications were mainly ischemic (56.30%) and infectious (39.10%). Among ischemic complications, sickle cell retinopathies and aseptic osteonecrosis are the most common with 59.20% and 31.63% respectively. Infectious complications were dominated by ENT (36.76%) and osteoarticular (35.29%) infections. Only age had an influence on the occurrence of ischemic complications (p = 0.0001). The probability of survival at 5 years was 99.38% and that at 20 years was 91.57%. The overall survival was not influenced by evolutionary complications.Conclusions: Infectious and ischemic evolutionary complications show the importance of vaccination and an early screening program.

Anemias ferropénicas asociadas a hemoglobinopatías en comunidades afrodescendientes en Colombia / Ferropenic anemia associated with hemoglobinopathies in Afro-descendant communities in Colombia

Resumen Objetivo. Determinar la presencia de anemias ferropénicas asociadas a hemoglobinopatías en afrodescendientes adultos colombianos habitantes de la ciudad de Tumaco, en el Departamento de Nariño y residentes de la localidad de Engativá, en Bogotá. Metodología. Las pruebas consideradas en este estudio incluyeron la valoración del hemograma automatizado, frotis de sangre periférica, proteína C reactiva, ferritina Sérica, electroforesis de hemoglobina, en 103 participantes, 23 de la comunidad afrodescendiente de Engativá y 80 de Tumaco. Esta investigación es de tipo descriptivo; por su enfoque metodológico es cuantitativa y transversal; estructurada, no experimental y correlacional, cuyo diseño muestral es estratificado, no probabilístico de tipo intencional. Resultados. La población en estudio perteneciente a la comunidad afrodescendiente ubicadas en las localidades de Tumaco, Nariño y Engativá de la ciudad de Bogotá, presentó anemia en la población femenina 28.6 % y la masculina 16.0 %. Se observó que el 9.7 % de la población en estudio, presenta hemoglobina y ferritina baja, relacionado con anemia por deficiencia de hierro y el 13.6 % presenta una deficiencia subclínica de hierro al presentar deficiencia de hierro sin anemia. Con respecto a los resultados de electroforesis de hemoglobina, el 13.6 % se evidenció con hemoglobina A2 aumentada, con posible asociación a talasemias o hemoglobinopatía C, el 0.98 % con hemoglobina S, el 0.98 % con rasgo de hemoglobina S y el 84.5 % con hemoglobina A. El 0.97 % de la población presenta ferritina baja con hemoglobina A2 aumentada, mostrando deficiencia de hierro asociada con posible hemoglobina C o talasemia y el 0.97 % de la población presenta ferritina baja con hemoglobina S. Otro hallazgo importante es la presencia de valores bajos de ferritina en el 17.8 % de las mujeres y el 4.95 % en hombres. Las variables cuantitativas se analizaron con medidas de tendencia central como el promedio y se describieron por medio de frecuencias absolutas y porcentuales.

Abstract Objective. To determine the presence of iron-deficiency anemia associated with haemoglobin disorders in adult people of African descent in the city of Tumaco, Nariño and residents of the town of Engativa, Bogota, Colombia. Methodology. The evidence considered in this study included the assessment of automated hemogram, peripheral blood, protein C reactive, ferritin serum, 103 participants, hemoglobin electrophoresis, distributed in 23 subjects in Engativá and 80 in Tumaco. This research study is descriptive; its methodological approach is quantitative and cross-sectional; structured, non-experimental and correlational, whose sample design is stratified, intentionally non-probabilistic. Results. The study community of Afro-descendants located in the towns of Tumaco Nariño and Engativa, Bogotá, present anemia in the female population of 28.6 % and in the male population of 16.0 %. It was observed that the 0.97 % of the population under study, shows hemoglobin and low ferritin, iron deficiency anemia-related. With respect to haemoglobin, at 13.6 % show increased hemoglobin A2, with possible association with thalassemia or hemoglobin C 0.98% and 0.98 % hemoglobin S. and 84.5 % with hemoglobin A, 0.97 % of the population have low ferritin with hemoglobin A2 increased, showing iron deficiency associated with possible C hemoglobin or thalassemia, and 0.97 % of the population have low ferritin with hemoglobin S. Another important finding is the presence of low levels of ferritin in 17.8 % of the women and the 4.95 % of the men indicating subclinical iron deficiency. The quantitative variables were analyzed using measures of central tendency as the average and described by means of absolute and percentage frequencies.

Técnicas convencionales aplicadas al diagnóstico de las hemoglobinopatías / Conventional techniques applied to the diagnosis of hemoglobinopathies / Técnicas convencionais aplicadas ao diagnóstico das hemoglobinopatias

Las hemoglobinopatías son trastornos hereditarios debidos a una gran variedad de defectos que afectan a los genes de globina. El diagnóstico de las hemoglobinopatías resulta de una combinación de estudios clínicos, pruebas de laboratorio y estudio familiar. Las herramientas básicas incluyen hemograma, hemoglobina e índices eritrocitarios (VCM, HCM), morfología de los eritrocitos, recuento de reticulocitos y perfil de hierro. Las determinaciones complementarias son electroforesis de hemoglobina que permite separar las diferentes variantes de acuerdo con su carga eléctrica, cuantificación de hemoglobina A2 (HbA2), Fetal (Hb F), pruebas de solubilidad hemoglobínica y falciformación. Otras técnicas se basan en propiedades fisicoquímicas como la estabilidad de la hemoglobina para detección de variantes inestables. En la práctica las pruebas más útiles son las que permiten detectar la presencia de hemoglobinopatías, como ocurre con la hemoglobina S dejando para laboratorios especializados aquellos procedimientos para identificar la mutación. La correcta detección de los portadores de las diferentes hemoglobinopatías tiene como finalidad dar un consejo genético adecuado sobre la forma de herencia, el riesgo de tener hijos afectados con las formas graves de la enfermedad y evitar tratamientos innecesarios. El diagnóstico molecular se reserva para la alfa talasemia, para cuadros con genotipos complejos, estudios prenatales o epidemiológicos.

Hemoglobinopathies are hereditary syndromes determined by a large variety of globin gene defects. Hemoglobinopathy diagnosis results from the combination of clinical orientation, laboratory tests and family studies. Basic tools include complete blood cell count, red blood cell count, hemoglobin quantification and red cell indices (MCV, MCH), blood film examination, reticulocyte count and iron status. Complementary determinations are hemoglobin electrophoresis, which enables the separation of the different hemoglobin variants according to their electrical charge, A2, and Fetal hemoglobin quantification, hemoglobin solubility and sickling test for Hb S diagnosis. Other techniques are based on physicochemical properties such as stability of hemoglobin for detection of unstable variants. In practice, the most useful tests are those that enable the detection of hemoglobinopathies, such as hemoglobin S, and the identification of the genetic defects is referred to specialized laboratories. The correct detection of the carriers of the different hemoglobinopathies is intended to give adequate genetic advice on the form of inheritance and the risk of having affected children with the severe forms of the disease and to avoid unnecessary treatments. Molecular diagnosis is reserved to a thalassemia complex genotypes, prenatal o epidemiological studies.

As hemoglobinopatias são distúrbios hereditários resultantes de uma grande variedade de defeitos que afetam os genes de globina. O diagnóstico das hemoglobinopatias decorre de uma combinação de estudos clínicos, provas de laboratório e estudo familiar. As ferramentas básicas incluem hemograma, hemoglobina e índices eritrocitários (VCM, HCM), morfologia dos eritrócitos, contagem de reticulócitos e perfil de ferro. As determinações complementares são eletroforese de hemoglobina que permite separar as diferentes variantes, de acordo com sua carga elétrica, quantificação de hemoglobina A2 (HbA2), Fetal (Hb F), provas de solubilidade hemoglobínica e falciformação. Outras técnicas baseiam-se em propriedades fisicoquímicas como a estabilidade da hemoglobina para detecção de variantes instáveis. Na prática, as provas mais úteis são as que permitem detectar a presença de hemoglobinopatias, como acontece com a hemoglobina S deixando para laboratórios especializados aqueles procedimentos para identificar a mutação. Detectar corretamente os portadores das diferentes hemoglobinopatías visa a dar um conselho genético adequado sobre a forma de herança, o risco de ter filhos afetados com as formas graves da doença e evitar tratamentos desnecessários. O diagnóstico molecular se reserva para a alfa talassemia, para quadros com genótipos complexos, estudos pré-natais ou epidemiológicos.

Hemoglobinopatia SD apresentada como hemoglobinopatia SS / Hemoglobinopathy SD presenting as Hemoglobinopathy SS

Este relato de caso mostra a interação da hemoglobina (Hb) S com a Hb D de uma criança que foi previamente diagnosticada como anemia falciforme (Hb SS) devido ao seu padrão de migração da eletroforese em pH alcalino. O fenômeno de falcização foi confirmado com 2% de metabissulfito de sódio. O pai e a mãe da criança apresentaram um padrão heterozigoto na eletroforese de hemoglobina em pH alcalino (Hb AS). O fenômeno de falcização foi confirmado para o pai, porém não foi confirmado para a mãe. A eletroforese em pH ácido foi realizado para diferenciar a Hb S da Hb D. O fenótipo da família foi estabelecido: o pai apresenta Hb AS, a mãe AD e a criança SD. O propósito do presente estudo foi ressaltar a importância da confirmação da Hb S detectada na eletroforese em pH alcalino, com o teste de solubilidade ou falcização e com a eletroforese em pH ácido. (AU)

This case report shows the interaction of hemoglobin (Hb) S with Hb D. in a child previously diagnosed with sickle cell anemia based on the Hb electrophoretic migration pattern in alkaline pH. The sickling phenomenon was confirmed with 2% sodium metabisulfite. The father and mother of the child had a heterozygous pattern (Hb AS) in hemoglobin electrophoresis at alkaline pH. The sickling phenomenon has been confirmed to the father, but it has not been confirmed for the mother. The electrophoresis at acid pH was used to differentiate Hb S from Hb D. The family's phenotype was established: the father has Hb AS, the mother AD and, the child SD. The purpose of this study was to emphasize the importance of confirmation of Hb S detected in electrophoresis at alkaline pH, with the solubility test or 2% sodium metabisulfite and with the electrophoresis at acid pH. (AU)

Clinical and laboratory profile of patients with sickle cell anemia

Abstract Objective: This study aimed to describe and analyze clinical and laboratory characteristics of patients with sickle cell anemia treated at the Hemominas Foundation, in Divinópolis, Brazil. Furthermore, this study aimed to compare the clinical and laboratory outcomes of the group of patients treated with hydroxyurea with those patients that were not treated with hydroxyurea. Methods: Clinical and laboratorial data were obtained by analyzing medical records of patients with sickle cell anemia. Results: Data from the medical records of 50 patients were analyzed. Most of the patients were female (56%), aged between 20 and 29 years old. Infections, transfusions, cholecystectomy, splenectomy and systemic arterial hypertension were the most common clinical adverse events of the patients. The most frequent cause of hospitalization was painful crisis. The majority of patients had reduced values of hemoglobin and hematocrit (8.55 ± 1.33 g/dL and 25.7 ± 4.4%, respectively) and increased fetal hemoglobin levels (12 ± 7%). None of the clinical variables was statistically significant on comparing the two groups of patients. Among hematological variables only hemoglobin and hematocrit levels were statistically different between patients treated with hydroxyurea and untreated patients (p-value = 0.005 and p-value = 0.001, respectively). Conclusion: Sickle cell anemia requires treatment and follow-up by a multiprofessional team. A current therapeutic option is hydroxyurea. This drug reduces complications and improves laboratorial parameters of patients. In this study, the use of the drug increased the hemoglobin and hematocrit levels of patients.

Clinical, hematological and genetic data of a cohort of children with hemoglobin SD

Introduction The hemoglobin FSD is very uncommon in newborn screening programs for sickle cell disease. In the program of Minas Gerais, Brazil, the clinical course of children with hemoglobin SD was observed to be heterogeneous. The objective of this study was to estimate the incidence (1999­2012) and to describe the natural history of a cohort of newborns with hemoglobin SD. Methods Isoelectric focusing was the primary method used in newborn screening. Polymerase chain reaction-restriction fragment length polymorphism and gene sequencing were used to identify mutant alleles and for haplotyping. Gap-polymerase chain reaction was used to detect alpha-thalassemia. Results Eleven cases of hemoglobin S/D-Punjab and eight of Hb S-Korle Bu were detected. Other variants with hemoglobin D mobility were not identified. All hemoglobin D-Punjab and hemoglobin Korle Bu alleles were associated with haplotype I. Among the children with hemoglobin S/D-Punjab, there were four with the ßS CAR haplotype, six with the Benin haplotype, and one atypical. Results of laboratory tests for hemoglobin S/D-Punjab and hemoglobin S-Korle Bu were: hemoglobin 8.0 and 12.3 g/dL (p-value <0.001), leukocyte count 13.9 × 109/L and 10.5 × 109/L (p-value = 0.003), reticulocytes 7.5% and 1.0% (p-value <0.001), hemoglobin F concentration 16.1% and 6.9% (p-value = 0.001) and oxygen saturation 91.9% and 97% (p-value = 0.002), respectively. Only hemoglobin S/D-Punjab children had acute pain crises and needed blood transfusions or hydroxyurea. Those with the Benin ßS haplotype had higher total hemoglobin and hemoglobin F concentrations compared to the CAR haplotype. Transcranial Doppler was normal in all children. Conclusion The clinical course and blood cell counts of children with hemoglobin S/D-Punjab were very similar to those of hemoglobin SS children. In contrast, children with hemoglobin S-Korle Bu had clinical course and blood cell counts like children with the sickle cell trait.

Relationship between the prevalence of hemoglobin S and the ethnic background of blood donors in Paraná state / Relação entre prevalência da hemoglobina S e origem étnica de doadores de sangue no estado do Paraná

ABSTRACTIntroduction:Hemoglobin S (HbS) is one of the most common inherited hematological disorders in humans. In Brazil, the sickle-cell disease (SCD) has significant epidemiological importance due to its prevalence and the morbidity-mortality and, therefore, it has been identified as a matter of public health.Objective:To determine the prevalence of HbS among Asian Brazilian, Afro Brazilian, and Euro Brazilian individuals of a blood bank in Curitiba.Material and method:The study was conducted from January 2008 to December 2009, and included 83,213 donors seen at the Instituto Paranaense de Hemoterapia e Hematologia.Results and discussion:The prevalence of HbS in the studied population was 0.9%, among them, 0% Asian Brazilians, 2.7% Afro Brazilians, and 0.7% Euro Brazilians. There was a positive association, statistically significant for the sickle cell trait in Afro-descendants, with odds ratio (OR) 4.01; confidence interval (CI) 3.42-4.72; and 95% confidence.Conclusion:This study showed higher rates of sickle cell trait in Afro Brazilians, which corroborates data published in other Brazilian regions and states.

RESUMOIntrodução:A hemoglobina S (HbS) é uma das alterações hematológicas hereditárias de maior frequência na espécie humana. No Brasil, a anemia falciforme (AF) tem importância epidemiológica significativa em virtude da prevalência e da morbimortalidade que apresenta e por isso tem sido apontada como uma questão de saúde pública.Objetivo:Determinar a prevalência de HbS entre indivíduos de origem asiática, afro e euro-brasileira de um banco de sangue de Curitiba.Material e método:O estudo foi realizado no período de janeiro de 2008 a dezembro de 2009, no qual foram incluídos 83.213 doadores atendidos no Instituto Paranaense de Hemoterapia e Hematologia.Resultados e discussão:A prevalência geral de HbS na população estudada foi de 0,9%, sendo 0% entre asiático-brasileiros, 2,7% entre afro-brasileiros e 0,7% entre euro-brasileiros. Houve associação positiva, significativa estatisticamente, para o traço falcêmico nos afrodescendentes, com odds ratio (OR) de 4,01 e intervalo de confiança (IC) 3,42-4,72, com 95% de confiança.Conclusão:O presente trabalho demonstrou maiores índices de traço falcêmico em afro-brasileiros, o que corrobora dados publicados em outras regiões e estados brasileiros.

Sobre escravos e genes: “origens” e “processos” nos estudos da genética sobre a população brasileira / On slaves and genes: “origins” and “processes” in genetic studies of the Brazilian population

Neste artigo examino como geneticistas contemporâneos que pesquisam a história e a configuração da população brasileira interagem com outras disciplinas. Para tanto, tomei como estudo de caso artigos publicados por geneticistas que investigam a presença de variantes da hemoglobina S no Brasil, os quais pretendem claramente contribuir para a análise de questões como escravidão ou identidade étnica no país. Contrastando esses estudos com trabalhos contemporâneos da história e das ciências sociais, problematizo a centralidade explanatória da “origem” nos estudos genéticos analisados, bem como a falta de interação com questões epistemológicas de outras áreas do saber.

In this article I examine how contemporary geneticists investigating the history and configuration of the Brazilian population engage with other academic disciplines. To do so I use as a case study some articles published by geneticists researching the presence of hemoglobin S variants in Brazil, in which there is a clear pretension to contribute to the analysis of issues such as slavery or Brazil’s ethnic identity. By contrasting these studies with contemporary works from history and the social science, the explanatory centrality of “origin” in the genetic studies analyzed is problematized, as is the lack of interaction with the epistemological characteristics of other areas of knowledge.

Detección de hemoglobina S en neonatos del estado venezolano de Carabobo / Hemoglobin S detection in neonates of the Venezuelan state of Carabobo

Se efectuó un estudio descriptivo de 129 neonatos de ambos sexos, nacidos en la Unidad de Neonatología de un Centro de Salud Pública de la ciudad de Puerto Cabello, estado venezolano de Carabobo, desde enero de 2012 hasta junio de 2013, a fin de detectar tempranamente los recién nacidos con hemoglobina S. En la serie predominó el sexo femenino (51,9 %). Se empleó la técnica de electroforesis y se encontró hemoglobina normal (Hb A) en 91,5 %, así como patrones electroforéticos de hemoglobina anormal compatibles con Hb S en 8,5 %. De los 11 casos positivos, 90,9 % correspondieron a Hb SA y 9,1 % a Hb SS. La frecuencia de hemoglobina SA y SS detectadas, aun cuando no se pudieron establecer resultados diagnósticos, representó una alerta para implementar la detección inicial, que condujera a un programa de prevención precoz, y a la profilaxis desde los primeros meses de vida.

A descriptive study of 129 neonates of both sexes, born in the Neonatology Unit of a Public Health Center from Puerto Cabello city, Venezuelan state of Carabobo, was carried out from January, 2012 to June, 2013, in order to detect early newborns with hemoglobin S. In the series the feminine sex prevailed (51.9%). The electrophoresis technique was used and normal hemoglobin (Hb A) was found in 91.5%, as well as electrophoretic patterns of abnormal hemoglobin compatible with Hb S in 8.5%. Of the 11 positive cases, 90.9% corresponded to Hb SA and 9.1% to Hb SS. The detected hemoglobin SA and SS frequency, even when diagnostic results could not be established, represented a warning to implement the early detection, which conducted to a program of early prevention, and to prophylaxis from the first months of life.

Scope and efficiency of the newborn screening program in identifying hemoglobin S

Background: In 2001, the Brazilian Ministry of Health added hemoglobinopathies to the National Neonatal Screening Program to be implemented in three steps. In order to meet the proposed goals, it is crucial to establish periodic assessments of this program with the aim of monitoring its implementation. Objective: To assess the scope and the efficiency of the stages of the National Newborn Screening Program in identifying hemoglobin S. Methods: A cross-sectional study was developed with the results of the heel prick test using the high performance liquid chromatography method for babies born in Mato Grosso do Sul from 2006 to 2010. The following variables were investigated: year, number of live births, total screening, coverage ratio, prevalence, time between the child birth and the blood collection; age at diagnosis; age at the time of the first consultation; and time between the diagnosis and the first appointment. Results: Over the five years of the study, the mean coverage rate was 91.77%.The prevalences of hemoglobin FAS and hemoglobin FS were 1.65% and 0.011%, respectively. Blood samples from 43.48% of children were collected from the second to the seventh day. The age at diagnosis was within the first 28 days in 87.80% of the screened children. The lowest mean indices for the first consultation and the time between the diagnosis and the first appointment (58.8 and 46.4 days, respectively) occurred in 2010. Conclusions: The scope of the National Neonatal Screening Program for hemoglobinopathies is good, with a large number of individuals being tested. Efficiency is a suitable indicator to assess the program steps. Three points are recommended: the training of the individuals involved, studies to assess the assistance provided to the affected child, and genetic counseling to the mothers. .

Cuidados prestados pelas mães aos filhos com doença falciforme: superando desafios / Care provided by mothers to their children with sickle cell disease: overcoming challenges

A doença falciforme é a alteração hematológica de ordem genética mais frequente no mundo. Originou-se no continente africano há milhares de anos, chegou ao Brasil no período da escravidão. A alteração causa vaso-oclusão na microvasculatura e hemólise crônica, crises álgicas, infecções, icterícia e anemia, retardo do crescimento e desenvolvimento. O diagnóstico precoce com ênfase em ações preventivas minimiza essas ocorrências. Considerando esse contexto, o objetivo desta pesquisa foi compreender como as mães vivenciam os cuidados aos filhos com doença falciforme, em São Francisco do Conde ­ Bahia. Trata-se de um estudo descritivo, qualitativo. Os sujeitos foram 15 mães de crianças com doença falciforme residentes naquele município. A coleta de dados ocorreu nos seus domicílios, entre abril e maio de 2011, por meio de entrevista semiestruturada. Os dados foram analisados segundo a análise de conteúdo, constituindo três categorias: conhecendo a doença do filho; cuidando do filho com doença falciforme e enfrentando dificuldades para cuidar do filho com doença falciforme. O estudo revelou que as mães têm dificuldade de cuidar do filho após o diagnóstico por desconhecerem a doença, mas que, após as consultas e o convívio com o filho, elas se adaptaram à situação e passaram a ter menos dificuldades para cuidá-lo. As crianças são atendidas nos ambulatórios de referência, em Salvador. As mães realizam as medidas preventivas das complicações como: hidratação, antibióticoprofilaxia e atualização vacinal e sabem manejar os episódios de dor e febre, mas não sabem as atividades físicas que os filhos podem fazer e nem mensurar o baço. Demonstraram que cuidar dessas crianças é desgastante, pois requer inúmeras atividades, as quais assumem sozinhas. A escassez de recursos financeiros dificulta o deslocamento a Salvador para realizar consultas e as vacinas especiais. Espera-se que este estudo contribua para reflexões e ações que resultem na inserção da enfermeira no processo de cuidar da criança com doença falciforme e sua família e que as políticas públicas voltadas para as pessoas com essa patologia sejam postas em prática nos serviços de saúde.(AU)

Prevalencia de hemoglobinopatía Sy perfil hematológico de individuos con malaria, Quibdó-Chocó, 2011 / Prevalence of hemoglobinopathy S and hematological profile of individuals with malaria, Quibdó-Chocó, 2011

La malaria constituye un problema de salud pública grave en los países del trópico y se cree que la hemoglobina S podría conferir protección contra la malaria grave. Objetivo: determinar la prevalencia de la hemoglobina S y el perfil hematológico en individuos con malaria, Quibdó-Chocó. Materiales y métodos: estudio descriptivo transversal en 177 sujetos con malaria; se empleó fuente primaria de información basada en una encuesta estructurada, la determinación del perfil hematológico, el diagnóstico de malaria, la prueba de ciclaje y la electroforesis dehemoglobina para identificar la hemoglobina S. Se calcularon las medidas de frecuencia y de resumen, los intervalos de confianza para proporciones y las pruebas de estadística paramétrica y no paramétrica. Resultados: el 59% de los casos correspondieron a malaria por Plasmodium falciparum, el 35% a Plasmodium vivax y el 6% a malaria mixta; la prevalencia de anemia fue del52% y de hemoglobinopatía S del 1,1%. Adicionalmente, se hallaron diferencias estadísticas en la prevalencia de anemia según la raza, el sexo y la edad, mientras que la frecuencia de anemiano presentó diferencias en el análisis de la densidad parasitaria y el tipo de infección malárica. Conclusión: la prevalencia de hemoglobinopatía S fue menor de la esperada para esta población; la prevalencia de anemia fue muy alta, lo que evidencia un elevado riesgo para la salud individual y la calidad de vida en general.

Malaria is a serious public health issue worldwide, especially in tropical countries;it is believed that hemoglobin S could protect against severe malaria. Objective: to determine theprevalence of hemoglobin S and assess the hematological profile of individuals with malaria, inQuibdó-Chocó. Materials and methods: cross-sectional study of 177 patients with malaria. Theprimary source of information was based on a structured survey, determination of the completeblood count, malaria diagnosis, a sickle cell test, and a hemoglobin electrophoresis to identifyhemoglobin S. The measures of frequency and summary, the confidence intervals for proportions and the tests of parametric and nonparametric statistics were calculated. Results: 59% of thecases were positive for Plasmodium falciparum malaria, 35% for Plasmodium vivax malaria and 6%for mixed malaria; the prevalence of anemia was 52% and the hemoglobinopathy S prevalencewas 1,1%. Furthermore, statistical differences in the prevalence of anemia were found accordingto race, sex, and age, whereas the frequency of anemia did not show differences in the analysisin relation to parasite density and the type of malaria infection. Conclusion: for this population theprevalence of hemoglobin S was lower than expected. However, the prevalence of anemia was very high, which shows a high risk for individual health and for quality of life in general.