Anemia and hemoglobinopathies in pregnant women attended in a public hospital

Objectives: to identify the demographic profile and frequency of anemia and hemoglobinopathies, as a basis for future implementation of actions aimed at pregnant women in the public health domain. Method: this is a cross-sectional study developed with pregnant women attended in a university hospital at Mato Grosso do Sul, Brazil. Blood samples were collected for the erythrogram analysis for detection of anemia and selective and specific tests for abnormal hemoglobin. The patients regarded as indigenous and mentally ill, as well as inmates, were excluded from the research, as they represent a vulnerable population which needs a cohort different from that of the sample. For data collection, a particular questionnaire was used. The research was approved by the Ethics Committee of Universidade Federal de Mato Grosso do Sul (UFMS), under the Protocol 873/2006. Results: of the 215 pregnant women under study, 20% were adolescents; 36.3% had incomplete primary education; 53.0% were non-Caucasian; 43.3% were from Campo Grande, Mato Grosso do Sul, Brazil; and 21.1% were of European descent. 17.7% had some type of anemia and, in the evaluation of hemoglobinopathies, 4.7% of patients were detected with some abnormal hemoglobin, with the following frequencies: 3.3% with HbAS; 0.9% with HbAC; and 0.5% with intermediate β-thalassemia. Conclusion: the frequencies of anemia and hemoglobinopathy found in these pregnant women showed the importance of early diagnosis, revealing indicators able to provide a basis for preventive and assistance actions for adequate clinical monitoring, reducing maternal and neonatal morbimortality in the public health services. Descriptors: pregnant women; anemia; hemoglobinopathies; public health; nursing.

Prevenção de hemoglobinopatias a partir do estudo em gestantes

The Brazilian population, presents genes for abnormal hemoglobins with variable frequencies, which are influenced by the founding racial groups. Thus, the detection of carriers of the genetic alterations is important for public health, since they represent sources of new beterozygotes and possible homozygotes. The control of the hemoglobin pathologies has been possible by means of genetic counseling and early diagnosis. The clinical follow-up of the homozygotes and the orientation of the beterozygotes and especially the couples at risk represent a more effective mode of acting to avoid the birth of children who are carriers of a genetic disease, that is frequently lethal. For these reasons this work had as its objectives: to evaluate the importance of testing in pregnant women for the detection of hemoglobin pathologies with the purpose of investigating the prevalence, attaining prevention, a familial study and awareness; for the positive cases such as couples at risk, orient as to appropriate medical attendance; and to evaluate the response to the program. Of the total of 696 pregnant women analysed, 10.7% revealed hemoglobin pathologies with the following rates: alpha Thalassemia 6.75%; Hb AS 2.01%; beta minor Thalassemia 1.29%; Hb AC 0.28%; Hb AJ 0.14%; Hb AS/Alpha Thalassemia 0.14% and P.H.H.F. 0.14%. The high rates of hemoglobin pathologies encountered in the population of pregnant women studied shows the necessity of the implantation of tests for these abnormalities in the pre-natal routine, since in this period the mothers are more apt to be preoccupied with their own health and that of their babies and, however earlier diagnosed the alterations in the hemoglobins, better and more adequate will be the orientations given the couple.

Classificação e previsão de cardiotocogramas usando algoritmos baseados em redes neuronais

Mestrado em Computação e Instrumentação Médica

Rastreio Neonatal de Hemoglobinopatias numa População Residente em Portugal

The primary objective of newborn screening of hemoglobinopathies is the early identification of infants with sickle cell disease, as they are at increased clinical risk. Other goals include the identification of other types of clinically significant hemoglobinopathies and the detection of heterozygous carriers followed by the screening and counselling of family members. We performed a pilot study for the neonatal screening of hemoglobinopathies in 400 samples of cord blood taken from a maternity in Lisbon. We did not find any newborn with sickle cell disease. Six samples were from sickle cell heterozygotes, the respective families were studied and informed. We looked for the presence of alpha-thalassemia at birth in 100 consecutive samples of cord blood, by the presence of Hb Bart's, abnormal red blood cell indices and alpha-globin genotype. The results show an incidence of 10% of alpha-thalassemia (-alpha) carriers and 4% of triple alpha-globin gene carriers. The authors discuss the feasibility of neonatal screening of hemoglobinopathies in a Portuguese-speaking population consisting of a low prevalence of Hb S trait autoclonous group and a high prevalence immigrant minority

Actividade física e qualidade de vida na gravidez

Pouco se conhece acerca da actividade física e qualidade de vida da mulher na gravidez. Este estudo teve como objectivos 1) comparar os padrões de actividade física antes e durante a gravidez, 2) avaliar a percepção da qualidade de vida relacionada com a saúde durante os primeiros seis meses de gestação, e 3) comparar a percepção da qualidade de vida nas mulheres activas e insuficientemente activas considerando as recomendações de saúde pública. Método: Estudo longitudinal com 59 grávidas seleccionadas em consultórios médicos privados. Às 10-15 semanas foi recolhida informação sociodemográfica e médica, bem como informação sobre a actividade física três meses antes da concepção. Medidas de auto-relato foram administradas entre as 10-15 semanas e as 19-24 semanas de gestação para avaliar o tempo de actividade física (QAFG) (no trabalho, lazer, deslocações) e a qualidade de vida (SF-36). Resultados: A prevalência de actividade física recomendada é menor durante do que antes da gravidez (16.7% e 17.5% nos 1.º e 2.º trimestres, respectivamente vs. 47.4% antes da gravidez). Com a gravidez, não se verificaram alterações no tempo médio em diferentes tipos de actividade física, mas a actividade física no lazer registou uma diminuição significativa no 1.º trimestre face ao período anterior à concepção. Em comparação com uma amostra normativa de mulheres portuguesas, as grávidas apresentam, nos dois primeiros trimestres de gestação, uma percepção de qualidade da vida mais positiva na generalidade das dimensões do SF-36. No 2.º trimestre, o nível de limitação é significativamente maior nas dimensões físicas, à excepção da Dor Corporal, e nos resultados sumários do Componentes Físico e Mental. As mulheres que no 1.º trimestre atingem os níveis recomendados de actividade física no lazer (≥150 minutos por semana) apresentam melhor estado de saúde geral e estados de humor mais positivos do que as menos activas. Conclusão: A actividade física no lazer, embora diminua após a concepção, tem um impacto positivo na percepção do estado saúde geral e estados de humor da grávida, o que sugere a sua importância para a saúde da mulher também durante este período da vida.

Focalização isoelétrica na identificação das hemoglobinas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Investigação de hemoglobinopatias em sangue de cordão umbilical de recém-nascidos do Hospital de Base de São José do Rio Preto

As hemoglobinopatias são as doenças genéticas mais freqüentes na população humana. Cerca de 12 a 15% da população é portadora de uma ou mais formas de hemoglobinas anormais, resultando em um grande problema de saúde pública. O diagnóstico neonatal possibilita o tratamento e o aconselhamento genético precoce, incluindo a conscientização dos portadores sobre o risco do nascimento de homozigotos. O objetivo deste trabalho é apresentar os resultados da investigação de hemoglobinopatias em recém-nascidos do Hospital de Base de São José do Rio Preto. O estudo foi realizado em 913 amostras de sangue de cordão umbilical, que foram submetidas a testes eletroforéticos, bioquímicos e citológicos, específicos para análise de hemoglobinas. Foram identificadas 100 (10,95%) amostras com hemoglobinas anormais, das quais 40 (4,38%) com Hb Bart's, sugerindo alfa talassemia, 34 (3,72%) com Hb S, 23 (2,52%) com beta talassemia, duas (0,22%) com Hb C e uma (0,11%) amostra apresentou Hb rápida. A frequência elevada de alterações encontradas evidencia a necessidade da triagem neonatal de hemoglobinopatias que pode resultar em amplos benefícios para os portadores destas patologias e seus familiares.

Hemoglobin as AS/alfa talassemia - Importância diagnóstica

Sickle Cell disease is a generic term for a group of genetic disorders characterized by the predominance of hemoglobin S. These disorders include Sickle Cell anemia, the Sickle Cell beta Thalassemia syndromes and Hemoglobinopathies in which hemoglobin S is in association with another abnormal hemoglobin, such as hemoglobin S/C. The Sickle Cell trait (hemoglobin AS) associated with Alpha Thalassemia presents alterations in the red blood cells morphology, usually absent in the heterozygous for this hemoglobin variant. The interaction between hemoglobin Sand alpha Thalassemia has been described as one of the factors responsible for the improvement in the clinical picture of homozygous of hemoglobin S (Sickle Cell Anemia), decreasing the number of episodes of pain. The genetic mechanisms of this influence are evaluated using molecular analyses of the human globin genes. With the objective of verifying the presence of alpha Thalassemia in heterozygous of hemoglobin S, with anemia, sent to the Laboratory of Hemoglobins, Department of Biology, UNESP, São José do Rio Preto, SP, we analyzed 1002 blood samples with Sickle Cell trait, in the period from 1990 to 1998. The samples were picked with EDTA 5% as anticoagulant, after previous authorization of the carriers. Appropriated counseling and management requires definitive diagnosis. For the laboratorial diagnosis the blood samples were submitted to electrophoretic procedures in alkaline and acid pH and cytological evaluation of hemoglobin H. The electrophoretic procedures confirmed the presence of hemoglobin AS. The cytological evaluation evidenced the presence of alpha Thalassemia. Of this total analyzed, 16(1,59%) blood samples presented the association between hemoglobin AS and alpha Thalassemia and two individuals belonged of the same family. Our results addressed us to suggest to the routine laboratories, that is important to accomplish the research of alpha Thalassemia among the Sickle Cell trait, with anemia, to verify the interaction with alpha Thalassemia, supplying to the carriers a important information on its hematological profile, genetic pattern of hemoglobinopathies and the appropriated counseling. Rev.bras.hematol.hemoter.,2000,22(3):388-394.

Influência da pré-eclâmpsia na capacidade funcional de exercício

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Serum haptoglobin types in patients with hemoglobinopathies

Haptoglobin types were determined in 626 individuals living in the State of Sao Paulo (Brazil). Of these, 484 had Hb AA, 31 major beta thalassemia, 43 minor beta thalassemia, 14 Hb SS, and 54 Hb AS. Frequency distribution of the three most common types observed among patients with type beta thalassemia differed significantly from that observed in the Caucasian group with Hb AA. There was a significant increase in Hp 1-1, which led us to assume that these disorders participate in a selective process acting on haptoglobins and altering the equilibrium of their frequencies. This relationship was not observed when we compared patients with Hb SS and Hb AS with Black patients with Hb AA, although the type most often observed among patients with Hb SS was Hp 1-1. The distributions of Hp groups observed among Caucasian and Black patients with Hb AA were similar to those obtained by other investigators for the South and Southeast regions of Brazil, with the exception of Rio de Janeiro.

Elevated Hypercoagulability Markers In Hemoglobin Sc Disease.

Hemoglobin SC disease is a very prevalent hemoglobinopathy, however very little is known specifically about this condition. There appears to be an increased risk of thromboembolic events in hemoglobin SC disease, but studies evaluating the hemostatic alterations are lacking. We describe a cross-sectional observational study evaluating coagulation activation markers in adult hemoglobin SC patients, in comparison with sickle cell anemia patients and healthy controls. A total of 56 hemoglobin SC and 39 sickle cell anemia patients were included in the study, all in steady state, and 27 healthy controls. None of the patients were in use of hydroxyurea. Hemoglobin SC patients presented a significantly up-regulated relative expression of tissue factor, as well as elevations in thrombin-antithrombin complex and D-dimer, in comparison to controls (p<0.01). Hemoglobin SC patients presented lower tissue factor expression, and thrombin-antithrombin complex and D-dimer levels when compared to sickle cell anemia patients (p<0.05). Endothelial activation (soluble thrombomodulin and soluble vascular cell adhesion molecule-1), and inflammation (tumor necrosis factor-alpha) markers were both significantly elevated in hemoglobin SC patients when compared to controls, being as high as the levels seen in sickle cell anemia. Overall, in hemoglobin SC patients, higher hemolytic activity and inflammation were associated with a more intense activation of coagulation, and hemostatic activation was associated with two very prevalent chronic complications seen in hemoglobin SC disease: retinopathy and osteonecrosis. In summary, our results demonstrate that hemoglobin SC patients present a hypercoagulable state, although this manifestation was not as intense as that seen in sickle cell anemia.

Key Endothelial Cell Angiogenic Mechanisms Are Stimulated By The Circulating Milieu In Sickle Cell Disease And Attenuated By Hydroxyurea.

As hypoxia-induced inflammatory angiogenesis may contribute to sickle cell disease manifestations, we compared the angiogenic molecular profiles of plasma from sickle cell disease individuals and correlated these with in vitro endothelial cell-mediated angiogenesis-stimulating activity and in vivo neovascularization. Bioplex demonstrated that plasma from steady-state sickle cell anemia patients presented elevated concentrations of pro-angiogenic factors (Angiopoietin-1, basic fibroblast growth factor, vascular endothelial growth factor, vascular endothelial growth factor-D and placental growth factor) and displayed potent pro-angiogenic activity, significantly augmenting endothelial cell proliferation, migration and capillary-like structure formation. In vivo neovascularization of Matrigel plugs was significantly greater in sickle cell disease mice, compared with non-sickle cell disease mice, consistent with an upregulation of angiogenesis in the disease. In plasma from patients with hemoglobin SC disease without proliferative retinopathy, anti-angiogenic endostatin and thrombospondin-2 were significantly elevated. In contrast, plasma from hemoglobin SC individuals with proliferative retinopathy displayed a pro-angiogenic profile and had more significant effects on endothelial cell proliferation and capillary formation than plasma of patients without retinopathy. Hydroxyurea therapy was associated with significant reductions in plasma angiogenic factor profile, in association with an inhibition of endothelial cell-mediated angiogenic mechanisms and neovascularization. Thus, sickle cell anemia and retinopathic hemoglobin SC individuals present a highly angiogenic circulating milieu, capable of stimulating key endothelial cell-mediated angiogenic mechanisms. Combination anti-angiogenic therapy for preventing progression of unregulated neovascularization and associated manifestations in sickle cell disease, such as pulmonary hypertension, may be indicated; furthermore, the benefits and drawbacks of the potent anti-angiogenic effects of hydroxyurea should be clarified.

alpha-Globin genes: thalassemic and structural alterations in a Brazilian population

Seven unrelated patients with hemoglobin (Hb) H disease and 27 individuals with alpha-chain structural alterations were studied to identify the alpha-globin gene mutations present in the population of Southeast Brazil. The -alpha3.7, --MED and -(alpha)20.5 deletions were investigated by PCR, whereas non-deletional alpha-thalassemia (alphaHphalpha, alphaNcoIalpha, aaNcoI, alphaIcalpha and alphaTSaudialpha) was screened with restriction enzymes and by nested PCR. Structural alterations were identified by direct DNA sequencing. Of the seven patients with Hb H disease, all of Italian descent, two had the -(alpha)20.5/-alpha3.7 genotype, one had the --MED/-alpha3.7 genotype, one had the --MED/alphaHphalpha genotype and three showed interaction of the -alpha3.7 deletion with an unusual, unidentified form of non-deletional alpha-thalassemia [-alpha3.7/(aa)T]. Among the 27 patients with structural alterations, 15 (of Italian descent) had Hb Hasharon (alpha47Asp->His) associated with the -alpha3.7 deletion, 4 (of Italian descent) were heterozygous for Hb J-Rovigo (alpha53Ala->Asp), 4 (3 Blacks and 1 Caucasian) were heterozygous for Hb Stanleyville-II (alpha78Asn->Lys) associated with the alpha+-thalassemia, 1 (Black) was heterozygous for Hb G-Pest (alpha74Asp->Asn), 1 (Caucasian) was heterozygous for Hb Kurosaki (alpha7Lys->Glu), 1 (Caucasian) was heterozygous for Hb Westmead (alpha122His->Gln), and 1 (Caucasian) was the carrier of a novel silent variant (Hb Campinas, alpha26Ala->Val). Most of the mutations found reflected the Mediterranean and African origins of the population. Hbs G-Pest and Kurosaki, very rare, and Hb Westmead, common in southern China, were initially described in individuals of ethnic origin differing from those of the carriers reported in the present study and are the first cases to be reported in the Brazilian population.

Thalassemia intermedia as a result of heterozygosis for ß0-thalassemia and aaaanti-3.7/aa genotype in a Brazilian patient

We report a case in which the interaction of heterozygosis for both the ß0-IVS-II-1 (G->A) mutation and the aaaanti-3.7 allele was the probable cause for the clinical occurrence of thalassemia intermedia. The propositus, a 6-year-old Caucasian Brazilian boy of Portuguese descent, showed a moderately severe chronic anemia in spite of having the ß-thalassemia trait. Investigation of the alpha-globin gene status revealed heterozygosis for alpha-gene triplication (aaa/aa). The patient's father, also presenting mild microcytic and hypochromic anemia, had the same alpha and ß genotypes as his son, while the mother, not related to the father and hematologically normal, was also a carrier of the aaaanti-3.7 allele. The present case emphasizes the need for considering the possibility of alpha-gene triplication in ß-thalassemia heterozygotes who display an unexpected severe phenotype. The ß-thalassemia mutation found here is being described for the first time in Brazil.

Screening for mutations in human alpha-globin genes by nonradioactive single-strand conformation polymorphism

Point mutations and small insertions or deletions in the human alpha-globin genes may produce alpha-chain structural variants and alpha-thalassemia. Mutations can be detected either by direct DNA sequencing or by screening methods, which select the mutated exon for sequencing. Although small (about 1 kb, 3 exons and 2 introns), the alpha-globin genes are duplicate (alpha2 and alpha1) and highy G-C rich, which makes them difficult to denature, reducing sequencing efficiency and causing frequent artifacts. We modified some conditions for PCR and electrophoresis in order to detect mutations in these genes employing nonradioactive single-strand conformation polymorphism (SSCP). Primers previously described by other authors for radioactive SSCP and phast-SSCP plus denaturing gradient gel electrophoresis were here combined and the resultant fragments (6 new besides 6 original per alpha-gene) submitted to silver staining SSCP. Nine structural and one thalassemic mutations were tested, under different conditions including two electrophoretic apparatus (PhastSystem™ and GenePhor™, Amersham Biosciences), different polyacrylamide gel concentrations, run temperatures and denaturing agents, and entire and restriction enzyme cut fragments. One hundred percent of sensitivity was achieved with four of the new fragments formed, using the PhastSystem™ and 20% gels at 15ºC, without the need of restriction enzymes. This nonradioactive PCR-SSCP approach showed to be simple, rapid and sensitive, reducing the costs involved in frequent sequencing repetitions and increasing the reliability of the results. It can be especially useful for laboratories which do not have an automated sequencer.