PPG - Medicina (Hematologia)

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https://hdl.handle.net/11600/61354

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Navegando PPG - Medicina (Hematologia) por Orientador(es) "Figueiredo, Maria Stella Figueiredo [UNIFESP]"

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    Análise de marcadores de hemólise em portadores de anemia falciforme
    (Universidade Federal de São Paulo (UNIFESP), 2015-06-24) Mecabo, Grazielle [UNIFESP]; Figueiredo, Maria Stella Figueiredo [UNIFESP]; http://lattes.cnpq.br/0736747630522639; http://lattes.cnpq.br/2857067496381666; Universidade Federal de São Paulo (UNIFESP)
    A hemólise na Anemia Falciforme (AF) é um dos mecanismos associados às manifestações clínicas da doença. Ela é predominantemente extravascular, a partir da exposição de sinais clássicos de fagocitose no eritrócito (sinais "eat me") contrabalançados por sinais de inibição (?don?t eat me?). O restante da hemólise ocorre por via intravascular, o que resulta na liberação de Hb livre no plasma que, para ser depurada, necessita das proteínas haptoglobina e hemopexina. A hidroxicarbamida (HU), utilizada no tratamento da AF, apresenta entre seus efeitos redução da hemólise. No entanto, pouco se sabe sobre a ação da HU nestes mecanismos. Objetivos: Avaliar a importância de marcadores relacionados à hemólise em indivíduos com AF no estado basal, com e sem uso de HU. CASUÍSTICA: Foram avaliados 40 indivíduos adultos com AF (36 com diagnóstico SS e 4 com S?0-talassemia) acompanhados no Ambulatório de Anemias Hereditárias da EPM/UNIFESP. Estes foram distribuídos nos grupos: a) SS ?pacientes em estado basal sem HU (N=20); b) SS-HU - em uso de dose máxima tolerada de HU (N=20). O grupo controle (N=22) foi constituído por indivíduos saudáveis. O trabalho foi aprovado pelo Comitê de Ética em Pesquisa e todos os pacientes concordaram em participar, assinaram TCLE. Critérios de exclusão:gestantes e indivíduos em transfusão crônica. MÉTODOS: Avaliação laboratorial: hemograma, contagem de reticulóctios (Ret), hemoglobina fetal (HbF), bilirrubina indireta, desidrogenase lática (DHL) e isoformas, Hb livre plasmática (HbL), haptoglobina (Hp). Foram avaliados por citometria de fluxo: expressão de banda-3, fosfatidilserina), CD47, microvesículas (MCV), CD59, (FACSCalibur®, Software CellQuest, Becton Dickinson Biosciences®). Análise estatística: Kruskal-Wallis e Correlação de Spearman, com nível descritivo de 5%. Resultados/DISCUSSÃO: Como esperado, os grupos de pacientes (SS e SS-HU) apresentaram marcadores de hemólise significativamente diferentes do grupo Controle. A DHL apresentou forte correlação negativa com Hp e positiva com HbL, confirmando seu papel como marcador de hemólise intravascular. As isoformas DHL-1, -2 e -3 apresentaram forte correlação positiva com HbL, sugerindo que a DHL-3, com origem ainda pouco esclarecida, possa ser também marcador útil na hemólise. Dos marcadores de eriptose avaliados, observou-se aumento da expressão da banda-3 no grupo SS-HU em relação aos outros grupos. Houve diferença entre os três grupos estudados em relação a expressão do CD59. Além disso, a expressão do CD59 nas MCVs estava aumentada no grupo SS-HU e isso foi diferente em relação aos outros grupos. Conclusões: Apesar da importância do CD47 na eriptose, não foi observada diferença em sua expressão entre pacientes e controles. No entanto, a possibilidade de utilização da isoformas de DHL-3, tanto como marcador de hemólise quanto no monitoramento do uso de HU, necessita ser melhor explorado. O aumento da expressão da banda-3 na presença de HU parece ter um papel importante na reologia do eritrócito. A expressão elevada do CD59 no grupo SS-HU sugere que esta droga possa ter papel protetor na lise do eritrócito.
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    Determinação da frequência alélica de polimorfismos de nucleotídeo único e análise de sua aplicação clínica na monitorização de quimerismo pós transplante de células hematopoéticas
    (Universidade Federal de São Paulo (UNIFESP), 2013-07-31) Azevedo, Marily Maria de [UNIFESP]; Figueiredo, Maria Stella Figueiredo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The chimerism analysis has become a routine procedure after Allogeneic Hematopoietic Stem Cell transplantation (HSCT) for early detection of relapse or graft failure. In recent years, various techniques have been described to evaluate chimerism. The basic principle of its detection is the utilization of differences between recipient and donor genomes. The most commonly used method is based on amplification of small tandem repeats (STR), with sensitivity ranging from 1 to 5%. This method is useful for documenting graft, but it is not sufficient for the detection of minimal residual disease or early relapse; situations where medical intervention is urgently needed. Currently, the Single Nucleotide Polymorphisms (SNPs) appear to be useful as molecular markers for monitoring chimerism after HSCT due to their stability, specificity and can be analyzed using quantitative methods sensitive. Objectives: 1. To determine the frequency of 12 polymorphisms in the Brazilian population to use them as a basis in developing an informative panel for chimerism analysis. 2. To realize a comparative analysis of techniques, such as STR, TaqMan qPCR and LNA, for identification and quantification of SNPs performed on samples from Brazilian and Canadian populations. Methods: Analyses of allele frequencies of SNPs rs668, rs5984, rs1800734 and rs1799854 were performed by allele-specific PCR (ASO-PCR) in the Brazilian population. SNPs rs4880, rs2269848, rs163781, rs10757713, rs1432622, rs713503, rs2296600 and rs715463 were performed with TaqMan methodology (MGB) and LNA. Chimerism analysis techniques were performed used STR, TaqMan (MGB) and LNA. Results and Discussion: The SNPs analysis showed an allele frequency of approximately 50% for the ancestral allele for each SNP in the Brazilian and Canadian populations, suggesting this panel can be useful in the analysis of chimerism. However, more studies are needed to determine the informativity of this panel. Specific SNPs analysis using TaqMan technology (MGB) have proved to be useful in determining chimerism, despite initial difficulties for determine an informative panel. The LNA technology initially proved to be more sensitive and specific technique, however, its reproducibility was not effective. Typical assays for chimerism analysis are expensive and time consuming. Variations can occur between SNPs, so each SNP needs to be validated individually before its clinical application. TaqMan MGB technique was considered the best option to save time and money compared to LNA and STR. Conclusions: Despite its cost and time spent for its execution, STR is the gold standard test to monitor chimerism after HSCT mainly due to be commercially available. The studied SNPs appear to be useful as molecular markers for monitoring chimerism after HSCT due to the allele frequency presented. Genotyping using qPCR assay has the potential to reduce time and medical costs, important factors in developing countries, such as Brazil.
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    Estudo da anemia em longevos com independência funcional
    (Universidade Federal de São Paulo (UNIFESP), 2016-11-29) Moraes, Niele Silva de [UNIFESP]; Figueiredo, Maria Stella Figueiredo [UNIFESP]; http://lattes.cnpq.br/0736747630522639; http://lattes.cnpq.br/1140706468939596; Universidade Federal de São Paulo (UNIFESP)
    Lower levels of hemoglobin have been often observed in the elderly population, but it has been discussed whether anemia is a physiological consequence of aging or a negative clinical feature. Objetives: The aims of this study were to evaluate hemoglobin levels in a Brazilian population of oldest old with active aging; describe the prevalence and causes of anemia in this population and its impact on survival. Patients and Methods: This was a prospective observational study of community-dwelling independent elderly aged 80 years or older in the city of São Paulo, Brazil. Patients were excluded if institutionalized, diagnosed with dementia, Parkinson disease or current cancer, were under dialysis or were hospitalized in the last 3 months. Reference range of Hb levels was calculated e according to recommendations of the International Federation of Clinical Chemistry (IFCC). Results: Of 256 subjects included in this study, 182 (71%) were women, median age was 85 years old (80?99). A total of 47 individuals met exclusion criteria for statistical analysis. The median hemoglobin level was 13.9 g/dL in men and 13.3 g/dL in women. Calculated 0.95 reference range of hemoglobin concentration was 11.2-16.7g/dL for men and 11.3-15.7 g/dL in women. According to WHO criteria, 40 patients (15,6%) had anemia. The major cause of anemia was chronic kidney disease (CKD), present as single cause of anemia in 40.0% of patients. Iron deficiency was the second most common cause of anemia (37.5% of cases). Patients with anemia had significantly lower glomerular filtration rate (42.7ml/min/1.73m2 vs. 50.6 ml/min/1.73m2, P=0.001). There was a significant association between anemia and osteoporosis (P=0.045) and osteoarthritis (P<0.001). No difference in survival of patients with or without anemia was observed (74% vs. 84%, P=0.22). Conclusion: A lower threshold of hemoglobin was found for both men and women when compared to levels set by WHO. Most of cases of anemia were secondary to CKD, followed by iron deficiency. Anemia was not associated with inferior survival in functionally independent oldest old men or women. Further studies must contribute to indicate the normal level of hemoglobin concentration in the elderly and clarify if anemia is actually a marker of other clinical conditions that may impact on survival of the elderly population. contribute to indicate the normal level of hemoglobin concentration in the elderly.