Spatial distribution of newborns with sickle cell trait in sergipe, brazil / Distribuição espacial de recém-nascidos com traço falciforme em sergipe

ABSTRACT Objective: To use the spatial distribution of the sickle cell trait (SCT) to analyze the frequency of hemoglobin S (HbS) carriers in Sergipe. Methods: The sample consisted of all individuals born in Sergipe from October 2011 to October 2012 who underwent neonatal screening in the public health system. Tests were carried out in basic health units and forwarded to the University Hospital laboratory, where they were analyzed. We used spatial autocorrelation (Moran's index) to assess the spatial distribution of heterozygous individuals with hemoglobinopathies. Results: Among 32,906 newborns, 1,202 showed other types of hemoglobin besides Hemoglobin A. We found a positive correlation between the percentage of black and multiracial people and the incidence of SCT. Most SCT cases occurred in the cities of Aracaju (n=273; 22.7%), Nossa Senhora do Socorro (n=102; 8.4%), São Cristóvão (n=58; 4.8%), Itabaiana (n=39; 4.2%), Lagarto (n=37; 4.01%), and Estância (n=46; 4.9%). Conclusions: The spatial distribution analysis identified regions in the state with a high frequency of HbS carriers. This information is important health care planning. This method can be applied to detect other places that need health units to guide and care for sickle cell disease patients and their families.

RESUMO Objetivo: Basear-se na distribuição espacial do traço falciforme (TF) para analisar a frequência dos portadores da hemoglobina S (HbS) em Sergipe. Métodos: A amostra foi constituída por todos os indivíduos nascidos em Sergipe, no período de outubro de 2011 a outubro de 2012, submetidos à triagem neonatal pelo Sistema Único de Saúde, ano de início da triagem universal no Estado. Os testes foram realizados em unidades básicas de saúde e encaminhados para o laboratório do Hospital Universitário, onde foram analisados. A análise da distribuição espacial dos indivíduos heterozigotos para hemoglobinopatias foi realizada por autocorrelação espacial (índice de Moran). Resultados: Dentre os 32.906 recém-nascidos estudados, 1.202 apresentaram outras hemoglobinas além da Hemoglobina A. Houve correlação positiva entre a porcentagem de negros e mestiços e a incidência de TF. A maioria dos casos foi encontrada nos municípios de Aracaju (n=273; 22,7%), Nossa Senhora do Socorro (n=102; 8,4%), São Cristóvão (n=58; 4,8%), Itabaiana (n=39; 4,2%), Lagarto (n=37; 4,01%) e Estância (n=46; 4,9%). Conclusões: Na análise de distribuição espacial por autocorrelação, identificaram-se regiões no Estado com maior frequência de HbS, o que é de extrema importância para o planejamento do sistema de saúde, podendo a mesma metodologia ser aplicada para identificação de outros locais com maior necessidade de centros para cuidados e orientações a portadores de doença falciforme e seus familiares.

Anemia drepanocítica y embarazo. Experiencia en el Instituto de Hematología e Inmunología, Cuba / Sickle cell disease and pregnancy. Experience at the Instituto de Hematologia e Inmunología, Cuba

El embarazo en la anemia drepanocítica (AD) es considerado una situación de alto riesgo por la alta incidencia de la morbimortalidad materno-fetal. En Cuba, el programa de atención integral a las embarazadas se incluye desde el nivel primario de salud y la captación se realiza antes de las 12 sem de gestación y los partos son institucionales. Todas las embarazadas con AD en La Habana son atendidas en el Instituto de Hematología e Inmunología (IHI) por un equipo multidisciplinario y los partos se realizan en el Servicio de Obstetricia del Hospital General Docente Enrique Cabrera . Desde enero del año 2000 hasta diciembre del 2009, 68 embarazadas con AD fueron atendidas por un equipo multidisciplinario. La frecuencia de las consultas fue quincenal hasta las 32 sem de la gestación y posteriormente semanal hasta la sem 36 en que fueron ingresadas; el embarazo se interrumpió en la semana 38. Las pacientes que presentaron algún evento fueron hospitalizadas y en ellas la interrupción se realizó en la semana 36 si el feto era viable. El bienestar fetal fue evaluado desde la semana 28 cada 2 semana hasta el nacimiento. No se realizaron transfusiones ni exanguinotransfusiones profilácticas y solo fueron indicadas según los criterios del equipo médico tratante; 16 pacientes recibieron transfusiones de glóbulos y la exanguinotransfusión se realizo en 4, todas en el tercer trimestre del embarazo. En 47 pacientes se realizó cesárea y siempre por indicación obstétrica; 17 recién nacidos tuvieron bajo peso pero solo uno tuvo un conteo de Apgar bajo. Ocurrieron 2 muertes fetales y una neonatal; se reportó una muerte materna

Pregnancy in women with sickle cell disease (SCD) is a high-risk situation associated with increased incidence of maternal and fetal morbidity and mortality. In Cuba, the maternal care program includes the primary level and the gestational age at booking is before the 12 week of gestation and all deliveries are institutional. All pregnant women with SCD in La Habana are attended at the Institute of Hematology and Immunology (IHI) by a multidisciplinary team and labor takes place at the obstetrics service of the General Hospital next to the IHI. From January 2000 to December 2009, 68 pregnant women with SCD were attended in labor; the frequency of the visits is every two weeks from gestational age at booking until week 32 of pregnancy and weekly until week 36 when they are hospitalized, in week 38 induction of labor is made. Patients were hospitalized upon the appearance of any event and in such cases induction of labor was made in week 36, if fetus was mature. The fetal well-being was evaluated starting from week 28 and every two weeks until childbirth. Non prophylactic blood transfusion or prophylactic exchange transfusions were indicated as this depends on the criteria of attending team; only 16 patients presented alert signs of requiring blood transfusion, 4 requiring blood exchange transfusions. All these procedures were carried out in the third trimester of pregnancy; 47 patients required caesarea indicated by the obstetrician; 17 newborns were underweight but only one with low apgar score. Two fetal deaths occurred and one new born had early neonatal death. Only one maternal death was reported

Haplotipos del gen de la globina beta en portadores de hemoglobina S en Colombia / Beta globin haplotypes in hemoglobin S carriers in Colombia

Introducción. La mutación de la hemoglobina S (HbS) va acompañada por otras mutaciones en la región del cromosoma 11, conocida como conjunto de la globina beta(beta globin cluster). El patrón de combinación de estos polimorfismos da lugar a los haplotipos que se heredan junto con la mutación de la hemoglobina S, se denominan haplotipos de la mutación bs y revisten gran importancia epidemiológica y clínica. Objetivo. Determinar la frecuencia de los principales haplotipos asociados al gen HBB en pacientes colombianos heterocigotos para hemoglobina S. Materiales y métodos. En la Clínica Colsanitas se han estudiado a la fecha 1.200 muestras de sangre periférica de niños en busca de hemoglobinopatías, y se ha encontrado el rasgo falciforme como la hemoglobinopatía más frecuente. Se determinaron los haplotipos del gen HBB que presentaron la mutación beta-S en 33 niños con patrón electroforético de hemoglobina AS, mediante reacción en cadena de la polimerasa (PCR) y enzimas de restricción. Se determinaron el patrón electroforético de la hemoglobina, el nivel de hemoglobina fetal y los parámetros hematológicos de cada individuo. Resultados. Los haplotipos de la hemoglobina S encontrados con mayor frecuencia en la muestra analizada son de origen africano y su orden de aparición fue mayor para el haplotipo Bantú (36,4 %), seguido por Senegal (30,3 %), Benín (21,2 %) y Camerún (12,1 %). La electroforesis de hemoglobina confirmó el fenotipo AS; la dosificación de hemoglobina fetal mostró niveles por debajo de 1 % y los parámetros hematológicos analizados mostraron valores normales en el 100 % de los individuos. Conclusión. Los haplotipos de la HbS encontrados con mayor frecuencia en la muestra estudiada eran de origen africano y su distribución variaba de acuerdo con el lugar de prodedencia del individuo. La mayor frecuencia correspodió al haplotipo Bantú.

Introduction. The hemoglobin S (HbS) mutation is accompanied by other mutations in the region of chromosome 11 known as "beta globin cluster". The pattern of combination of these polymorphisms giving rise to the haplotypes that co-inherit the HbS mutation, are called haplotypes bs, and are of great epidemiological and clinical significance. Objective. The frequencies of major haplotypes associated with S beta-globin gene was determined in Colombian patients heterozygous for hemoglobin S. Materials and methods. As part of the national neonatal screening program at Clínica Colsanitas, located in major cities of Colombia, nearly 1,200 children from different areas of the country were examined for hemoglobinopathies. The sickle cell trait was identified as the most common. S beta-globin gene haplotypes were determined by PCR and restriction enzymes in 33 children with AS hemoglobin electrophoretic patterns (carrier state). In addition, electrophoretic patterns of hemoglobin, fetal hemoglobin levels and hematologic parameters of each individual were identified. Results. The most frequent haplotypes in Colombia were the Bantú haplotype (36.4 %), followed by Senegal (30.3 %), Benin (21.2 %) and Cameroon (12.1 %) haplotypes. Hemoglobin electrophoresis confirmed the AS phenotype in all patients, and fetal hemoglobin levels below 1%. Other hematological parameters were normal in all cases. Conclusion. The HbS haplotypes found more frequently in the sample were of African origin, and their distribution varied according to the place of origin of the individual. The most frequent corresponded to the Bantu haplotype.

Prevalência do traço e da anemia falciforme em recém-nascidos do Distrito Federal, Brasil, 2004 a 2006 / Prevalence of sickle cell trait and sickle cell anemia among newborns in the Federal District, Brazil, 2004 to 2006

Para determinar a prevalência da anemia e traço falciforme em recém-nascidos no Distrito Federal, Brasil, no período de 2004 a 2006, foi realizado um estudo seccional de prevalência. Foram utilizados os registros dos resultados de testes realizados de 2004 a 2006 pelo Programa de Triagem Neonatal da Secretaria de Estado de Saúde do Distrito Federal, e calculados os coeficientes de prevalência. As amostras de sangue dos recém-nascidos foram analisadas pela técnica de focalização isoelétrica. No período de 1º de janeiro de 2004 a 31 de dezembro de 2006, foram realizados 116.271 testes de triagem neonatal para hemoglobinopatias, correspondendo a 85 por cento do número de nascidos vivos de mães residentes no Distrito Federal. Foram identificados, nos três anos, 3.760 recém-nascidos, com traço falciforme (Hb AS) e 109 com anemia falciforme (Hb SS). Os coeficientes de prevalência foram, respectivamente, 323 (Hb AS) e 9 (Hb SS) por 10 mil nascidos vivos. A elevada prevalência do traço falciforme evidencia a importância da triagem neonatal no Distrito Federal para atuação de gestores e profissionais da saúde no planejamento de ações educativas e na redução da morbidade associada às doenças falciformes.

To determine the prevalence of sickle cell trait and sickle cell anemia among newborns in the Federal District, Brazil, a cross-sectional prevalence study covering the years 2004 to 2006 was conducted. Test results reported from the Neonatal Screening Program in the Federal District Health Department from 2004 to 2006 were analyzed, and prevalence rates were calculated. Neonatal blood samples were tested by isoelectric focalization. From January 2004 to December 2006, 116,271 newborns were tested for hemoglobinopathies, corresponding to 85 percent of all live births from mothers residing in the Federal District. The study identified 3,760 newborns with sickle cell trait (Hb AS) and 109 with sickle cell anemia (Hb SS). The prevalence rates were 323 (Hb AS) and 9 (Hb SS) per 10,000 live births. The high prevalence of sickle cell trait highlights the importance of neonatal screening in the Federal District to support work by health managers and professionals for planning educational measures and reducing the morbidity associated with sickle cell disease.

Haematological study in sickle cell homozygous and heterozygous children in the age group 0-6 years.

Sickle cell anaemia is a common and widespread haemoglobinopathy with large clinical heterogeneity. The present study, was undertaken to determine seven different haematological parameters (Haemoglobin percent, RBC count, PCV, MCV MCH, MCHC, Reticulocyte count) on total 102 heterozygous (SA) and homozygous (SS) sickle cell children under six years of age. In addition, fetal haemoglobin (HbF) level was estimated in SS children and correlated with clinical status, gender and ethnic background. Mean HbF was 16.79%. Higher HbF level was associated with less severe clinical feature. HbF was not influenced by gender and ethnic background. In homozygous children mean values of MCV, MCH, MCHC were decreased while reticulocyte count was increased as compared to control (AA) children and (SA) children (P < 0.05) We conclude that, in sickle cell disease, HbF was a good prognostic indicator. Higher HbF level along with microcytic hyopochromic indices and lower MCHC was found to be a feature of the study population.

Um caso de discriminação genética: o traço falciforme no Brasil / Genetic Discrimination: sickle cell trait in Brazil

Este artigo discute um caso de discriminação genética envolvendo uma atleta brasileira de voleibol identificada como portadora do traço falciforme. O traço falciforme é uma das características genéticas mais prevalentes na população brasileira, mas não é descrito como uma doença genética. O avanço da genética clínica vem provocando uma popularização dos testes genéticos em diferentes contextos de promoção da saúde. Ao criticar o argumento da Confederação Brasileira de Vôlei de que o exame para o traço falciforme seria uma medida de proteção à saúde dos atletas, o objetivo do artigo foi demonstrar como a popularização da informação genética não pode prescindir do aconselhamento genético e de garantias éticas. A análise mostrou que a exclusão da atleta da seleção oficial de vôlei não se justificou por medidas de proteção à saúde, mas por discriminação genética.

This paper analyses a case of genetic discrimination of a Brazilian volleyball athlete. A routine exam identified the sickle cell trait in her blood. The sickle cell trait is one of the most prevalent genetic information in Brazilian population, but it not considered a genetic disease. The advancement of clinical genetic promotes a popularization of genetic tests in different health care initiatives. The aims of this paper are: 1) to criticize the argument supporting the test for sickle cell trait as a health care initiative; 2) to demonstrate how the popularization of genetic information demands genetic counseling and ethical protections. The analysis demonstrates how the athlete exclusion from the official volleyball team is not supported by medicine and is a case of genetic discrimination.

HPLC determination of hemoglobins to establish reference values with the aid of statistics and informatics

The purpose of the present study was to establish reference values for hemoglobins (Hb) using HPLC, in samples containing normal Hb (AA), sickle cell trait without alpha-thalassemia (AS), sickle cell trait with alpha-thalassemia (ASH), sickle cell anemia (SS), and Hb SC disease (SC). The blood samples were analyzed by electrophoresis, HPLC and molecular procedures. The Hb A2 mean was 4.30 +/- 0.44% in AS, 4.18 +/- 0.42% in ASH, 3.90 +/- 1.14% in SS, and 4.39 +/- 0.35% in SC. They were similar, but above the normal range. Between the AS and ASH groups, only the amount of Hb S was higher in the AS group. The Hb S mean in the AS group was 38.54 +/- 3.01% and in the ASH it was 36.54 +/- 3.76%. In the qualitative analysis, using FastMap, distinct groups were seen: AA and SS located at opposite extremes, AS and ASH with overlapping values and intermediate distribution, SC between heterozygotes and the SS group. Hb S was confirmed by allele-specific polymerase chain reaction. The Hb values established will be available for use as a reference for the Brazilian population, drawing attention to the increased levels of Hb A2, which should be considered with caution to prevent incorrect diagnoses.

Study of haemoglobin S percentage and haematological parameters in sickle cell trait.

A total of 101 individuals who showed AS pattern on haemoglobin electrophoresis were included in this study and various haematological investigations were carried out on them. Of these, 79 cases were grouped as AS patients. Twenty two healthy relatives of sickle anemia patients were grouped as AS controls. Twenty AA controls were also included in this study. Haemoglobin S (HbS) and hemoglobin A (HbA) quantitation was carried out. The frequency distribution of HbS percentage showed that maximum subjects had HbS levels above 33%. A female predominance was seen in subjects of sickle cell trait. Haemoglobin levels and total red cell counts of AS patients were found to be significantly lower than those of AS controls. Reticulocyte counts and hematocrit values of AS patients were found to be significantly higher than AS controls. MCV and MCH values of AS patients were found to be significantly lower, but MCHC was not significantly altered.

Hemoglobinopathies among five major ethnic groups in Karachi, Pakistan.

A brief survey of abnormal hemoglobin variants among the major ethnic groups of Karachi was conducted; 202,600 subjects were studied. Patients with low hemoglobin (Hb), low mean cell volume (MCV) and mean cell hemoglobin (MCH) including anemia, microcytosis, hypochromic hemolysis and target cells, were refered for the identification of hemoglobinopathy by molecular methods. Population screening showed that 60% had iron-deficiency anemia and 40% had hemolytic anemia, of which 20.6% was due to beta-thalassemia major, 13% beta-thalassemia trait, 5.1% sickle cell disease, 0.76% hemoglobin D Punjab (HbD Punjab), 0.32% hemoglobin C (HbC), and 0.22% hereditary persistence of fetal hemoglobin (HPFH).

Clinical profile of sickle cell trait.

OBJECTIVES: Although sickle cell trait is considered a harmless condition in ordinary circumstances, a large number of pathological conditions have been attributed to it often without a scientific basis. Many patients visit this centre with various complaints and on testing are found to be sickle cell trait. Hence it was thought necessary to analyse these cases to find out the nature of their ailments. METHODS: Two hundred cases of sickle cell trait diagnosed by sickling test and hemoglobin electrophoresis on CAM, and 150 age and sex matched control cases with normal hemoglobin phenotype from a survey were studied. Hemoglobin estimation was done in all by cyanmethemoglobin method. Besides history and clinical examination other relevant investigations were done as necessary to arrive at the diagnosis. Seven cases of sickle cell trait were asymptomatic while the rest were suffering from different conditions. 51% of sickle cell trait and 86% of control cases had mild to severe anaemia which improved with iron therapy in trait cases. Hepatomegaly (11% vs 4.6%), epistaxis (5% vs 0.66%) and cholelithiasis (3% vs 0%) was seen in significantly more number in sickle cell traits than the control cases. Splenomegaly and midsystolic murmurs were present in higher percent of cases but was not statistically significant. There was one case of epilepsy with multiple small infarcts in the brain and another with focal fits with epileptogenic focus in the left cerebral hemisphere where no other cause could be found except sickle cell trait. CONCLUSION: The ailments of sickle cell trait cases are like persons with normal hemoglobin. Anaemia is not more frequent and can improve with iron therapy. However, hepatomegaly, epistaxis, cholelythiasis are seen more frequently and minor cerebral infarcts probably can occur in sickle cell trait. These require more elaborate studies to decide their pathogensis.

Serum lipids, ABO blood group and sickle cell trait.

One hundred apparently healthy individuals were used in this study. 71% of these had normal haemoglobin (HbAA) while 29% had sickle cell trait (HbAS). Serum cholesterol and phospholipids were investigated. The mean lipid and lipoprotein concentrations (cholesterol, high density lipoprotein cholesterol and phospholipid) were higher in the sickle cell trait than in the subjects with normal haemoglobin. When separated into blood groups, 24% belonged to the type A+, 11% to the type B+, 2% to the type AB+ and 63% to the type O+. In relation to sexes, a greater percentage of female population had higher lipid levels then the men, and this was consistent even in the sickle cell trait.

Amelioration of clinical severity through raised fetal hemoglobin in sickle cell anaemia.

In the present study, the levels of fetal hemoglobin (HbF) in sickle cell anemia patients were compared with sickle cell trait, beta thalassemia major and control. The mean HbF levels in beta thalassemia major and sickle cell anemia were 51.62 and 19.63% respectively. However, when the amount of HbF was expressed in terms of gram hemoglobin per deciliter whole blood, the mean values were 2.88 and 1.81 respectively between the two groups, suggesting that the genetic mechanism controlling the different threshold levels of increased HbF in these disorders could probably be similar. The elevated. HbF level in sickle cell anemia along with moderate hematologic profile observed in the present study is suggested to provide amelioration of the clinical severity unlike in beta thalassemia major where despite raised HbF levels, the severe clinical implications are attributed to marked imbalance in the globin chain synthesis.

Detection of alpha thalassaemia in sickle cell trait patients by Hb-Bart's screening & quantitation of Hb-A & Hb-S.

Haemoglobin fractionation in 27 subjects with sickle cell trait revealed 12 (44%) with sickle cell haemoglobin less than 35 per cent (23.4-34.2%, mean 30.4 +/- 3.3%) suggesting an association of alpha thalassaemia. Electrophoresis of 91 samples of cord blood revealed demonstrable amounts of haemoglobin Bart's in 7 (7.7%); six between 5 and 10 per cent and one with less than 2 per cent. It appeared that the six infants with higher amounts of haemoglobin Bart's were homozygous for alpha-thalassaemia + (-a/-a) genotypes and one was heterozygous for alpha-thalassaemia + (-a/aa) Results of haemoglobin electrophoresis done on 2754 blood samples analysed from hospital records, retrospectively did not reveal haemoglobin-H and haemoglobin Constant Spring in any of the samples.

Interaçäo entre beta-talassemia e estigma para hemoglobina S / Interacion between beta-thalassemia and sickle-cell trait

Säo analisados 67 casos de beta-talassemias em Salvador, Bahia. Discute-se a importância da associaçäo beta + talassemia e estigma para hemoglobina S

Sickle cell anemia in western Saudi Arabia

25 Saudi and Yemeni Arabs with sickle cell anemia from western Saudi Arabia aged between 5 and 30 years were studied. The mean study state haemoglobin concentration of 8 g/dl was lower than that of 10.7 g/dl reported previously for sickle cell anemia in Western Saudi Arabia. 14 patient had [HbF] of 10% or below [SSLF] while 11 patients had [HbF] above 10% [SSHF] No significant differences were found in the hemoglobin concentration and indices of the two groups. SSLF patients were significantly more prone to infection [P < 0.01], there was an overall high incidence of hepatomegaly [72%] and splenomegaly [60%]. Hepatomegaly was more common in the SSLF group [78.6%]. Saudi Arabian sickle cell anemia, even in patients with raised haemoglobin F levels, may be as clinically severe as in African patients

Hemograma em indivíduos com homozigose para hemoglobina A, estigmas AS e AC / Hemogram in patients with homozygosity for hemoglobin A, AS and AC traits

Säo analisados os resultados do hemograma de 990 indivíduos sem queixas clínicas, com homozigose para hemoglobina A (AA), com estigma para falcemia (AS) e com estigma para hemoglobina C (AC). Os estigmas para hemoglobina S têm hemotócrito, hemoglobina e contagem de hémacias com valores diferentes dos indivíduos AA. Os AC apresentam para estes mesmos exames valores semelhantes aos dos AA. Na contagem global de leucócitos näo existem diferenças significativas entre os AA, AS e AC