Varios fatores contribuem para o desenvolvimento da anemia, que constitui um dos mais graves problemas de saude publica. A anemia hipocromica microcitica e a forma mais comum em criancas e adolescentes. Dentre as causas desta anemia estao: a) deficiencia de ferro, que resulta de um longo periodo do balanco negativo do micronutriente e causa retardo no crescimento e comprometimento do desempenho cognitivo de criancas; b) contaminacao por chumbo (plumbismo) que tambem afeta o desenvolvimento das criancas, podendo ser agravada nos portadores de polimorfismo da enzima ALAD; c) hemoglobinopatias (hemoglobinas variantes e talassemias), anemias herdadas que afetam 7% da populacao mundial. Devido a alta prevalencia destas patologias, o presente trabalho teve como objetivo estudar um grupo de criancas de escolas publicas, identificando os fatores que contribuem para o desenvolvimento de anemias hipocromicas microciticas e estabelecer relacoes entre as caracteristicas laboratoriais das doencas. Participaram do estudo 427 criancas, com idade entre 6 a 9 anos, sendo 235 do sexo feminino e 192 do sexo masculino, alunos de Escolas Municipais e Estaduais, da zona norte da cidade de Ribeirao Preto-SP. Foram analisados: a) numero global de eritrocitos e leucocitos, concentracao de hemoglobina, hematocrito, indices hematimetricos e distribuicao da amplitude das celulas vermelhas (contador automatico Micros 45 . Horiba ABXR) e calculo do indice matematico RDWI; b) niveis plasmaticos de chumbo (espectrometro de massa com plasma indutivamente acoplado VG Plasmaquad PQIIR) e estudo das delecoes dos polimorfismos da enzima ALAD, por PCR; c) status ferrico pelos niveis de ferritina serica (imunoquimioluminescencia utilizando kit Ferritin Immulite . DPCR e equipamento Immulite 1 - DPCR), receptor de transferrina soluvel (ensaio imunoenzimatico, utilizando o kit Quantikine soluble transferrin receptor da R&D SystemsR e o leitor de microplacas de ELISA READER 210, modelo Microwell System Organon TeknikaR) e calculo do indice sTfR/log ferritina; d) analise das hemoglobinas por eletroforese em acetato de celulose, pH alcalino, por HPLC (sistema automatizado Variant II Bio-RadR e kit gÀ-talassemia Short Program) e PCR para a principal delecao de ¿- talassemias. Com base no criterio recomendado pela OMS para definir anemia (Hb menor que 11,5 g/dL), verificou-se que 75 (17,6%) criancas eram anemicas, sendo 33 (44%) portadoras de algum tipo de hemoglobinopatia, 29 (38,6%) com anemias de causa desconhecida e 13 (17,4%) com anemia por deficiencia de ferro. Das anemias, apenas 14 eram anemias hipocromicas microciticas, sendo que 10 (71,4%) eram algum tipo de hemoglobinopatia, 2 (14,2%) ADF e 2 (14,2%) de causa desconhecida. Na populacao estudada, a prevalencia de hemoglobinopatias foi de 16,6% , a saber: 11,6% com ¿-talassemia; 4% com aumento de Hb F; 3,5% com Hb AS; 2,8% com À-talassemia; 0,96% com ¿/À-talassemia e 0,24% com Hb AC. Os niveis de chumbo plasmatico, em todos os participantes do estudo, estavam dentro do recomendado pelo Center for Disease Control and Prevention (< 10 Êg/dL), nao havendo interferencia do metal na patogenese das anemias. Nao houve associacao entre os polimorfismos da ALAD-1 (ALAD1-1 e ALAD1-2) e os niveis de chumbo plasmatico. Anemia por deficiencia de ferro foi diagnosticada em 3% das criancas e DF em 6,1%, utilizando um cut off de 30 ng/mL para ferritina serica. Houve concordancia na identificacao de hemoglobinopatias utilizando as metodologias eletroforese de hemoglobina em acetato de celulose e HPLC, sendo que estas metodologias nao sao uteis para diagnosticar ¿-talassemia. Para identificar os portadores da delecao de ¿-talassemia (.¿3,7) e necessaria a utilizacao da análise molecular (PCR). A suspeita de Hb S/-talassemia identificada por HPLC deve ser confirmada por análise dos pais e/ou irmãos. A ferritina foi um bom parâmetro para identificar DF precocemente e útil para diferenciar os portadores de hemoglobinopatias dos portadores de DF e ADF. O índice sTfR/log da ferritina foi mais sensível do que o sTfR, na diferenciação de DF e talassemia. No diagnóstico das anemias hipocrômicas microcíticas é necessário analisar um conjunto de determinações, incluindo exame hematológico, status férrico, perfil eletroforético, em alguns casos incluindo avaliação dos familiares, e análise molecular das hemoglobinopatias. / Several factors contribute to the development of anemia, which constitutes one of the most serious problems in public health. The hypochromic microcytic anemia is the most common type in children and adolescents. Among the causes for this type of anemia are: a) iron deficiency, which results from a long period of negative balance of the micronutrient, causing delay in growth and compromising the cognitive performance of the children; b) contamination by lead (lead poisoning), which also affects the development of children, and may be aggravated in carriers of polymorphism of the enzyme ALAD; c) hemoglobinopathies (variants hemoglobin and thalassemia), inherited anemia that affects 7% of the world population. Due to the high prevalence of these pathologies, the present study aimed at studying a group of children from public schools, identifying the factors that contribute to the development of hypochromic microcytic anemia and establishing relations between the laboratorial characteristics of the diseases. The study had the participation of 427 children, aged between 6 and 9 years old, being 235 female and 192 male students from Municipal and State Schools in the north area of Ribeirao Preto-SP. It analyzed: a) number of erythrocytes and leucocytes, hemoglobin concentration, hematocrit, red cell indices and red cell distribution width (automatic counter Micros 45 . Horiba ABXR) and calculation of the mathematical index RDWI; b) plasma lead levels (inductively coupled plasma mass spectrometer VG PlasmaQuad PQIIR) and study of the deletions of the polymorphisms of the enzyme ALAD, by PCR; c) iron status by serum ferritin levels (immunochemiluminescence using the kit Ferritin Immulite . DPCR and the equipment Immulite 1 - DPCR), soluble transferrin receptor (enzyme immune assay, using the kit Quantikine soluble transferrin receptor of R&D SystemsR and the microplate reader ELISA READER 210, model Microwell System Organon TeknikaR) and calculation of the sTfR/log ferritin index; d) hemoglobin analysis by electrophoresis on cellulose acetate at alkaline pH, HPLC (automated system Variant II Bio-RadR and the kit gÀ-thalassemia Short Program) and PCR for the main deletion of ¿-thalassemias. Based on the WHO criteria by to define anemia (Hb under 11.5 g/dL), it was verified that 75 (17.6%) children were anemic, being 33 (44%) with hemoglobinopathy, 29 (38.6%) with anemia of unknown causes and 13 (17.4%) with iron deficiency anemia. Among the anemias, only 14 were hypochromic microcytic, 10 (71.4%) being some sort of hemoglobinopathy, 2 (14.2%) due to iron deficiency and 2 (14.2%) due to unknown causes. In the studied population, the prevalence of hemoglobinopathies was 16.6%, namely: 11.6% with ¿-thalassemia; 4% with Hb F elevated; 3.5% with Hb AS; 2.8% with À- thalassemia; 0.96% with ¿/À-thalassemia and 0.24% with Hb AC. The plasma lead levels, in all participants of the study, were within the levels recommended by the Center for Disease Control and Prevention (< 10 Êg/dL), without the interference of the metal in the pathogenesis of the anemias. There was no significant association between the polymorphisms of the ALAD-1 (ALAD1-1 and ALAD1-2) and the plasma lead levels. Iron deficiency anemia was diagnosed in 3% of the children and ID in 6.1%, using a cutoff of 30 ng/mL for serum ferritin. There was agreement in the identification of hemoglobinopathies using the methodologies electrophoresis of hemoglobin in cellulose acetate and the HPLC, as these methodologies are not useful to diagnose ¿-thalassemia. In order to identify the carriers of ¿-thalassemia gene deletion (.¿3,7) it is necessary to use the molecular analysis (PCR). The suspicion of Hb S/À-thalassemia identified by HPLC must be confirmed through the analysis iv of the parents and/or siblings. The ferritin was a good parameter to identify ID early and useful to differ the carriers of hemoglobinopathies of the carriers of ID and IDA. The sTfR/log ferritin level was more sensitive than the sTfR, in the differentiation of ID and thalassemia. In the diagnosis of the hypochromic microcytic anemias, it is necessary to analyze a set of determinations, including hematological exam, iron status, electrophoretic profile, in some cases including relatives, and molecular analysis of the hemoglobinopathies.

L’objectif de notre travail était de déterminer le rôle joué par l’érythropoïétine et la thrombopoïétine, respectivement, dans l’anémie et la thrombocytopénie observées chez des enfants souffrant d’une hémopathie maligne. Par le dosage simultané de la forme soluble du récepteur de la transferrine et de l’érythropoïétine dans le sérum nous avons montré que l’anémie observée chez ces patients est bien la conséquence d’une réduction du nombre de progéniteurs érythropoïétiques (atteinte médullaire centrale) mais que celle-ci n’est pas la conséquence d’une production insuffisante d’érythropoïétine. Nous avons fait la même observation chez des enfants souffrant d’une tumeur solide non hématologique et chez des patients en cours de traitement par chimiothérapie. Chez ces derniers patients, en appliquant un modèle de culture de moelle à long terme, nous avons pu démontrer l’existence d’une altération du microenvironnement médullaire, probablement induite par la chimiothérapie, se traduisant par une réduction de son aptitude à supporter le développement de la lignée érythroïde. Ceci expliquant au moins partiellement l’inadéquation de la réponse érythropoïétique observée chez ces patients en réponse à l’anémie. Dans la dernière partie du travail, nous avons montré que la thrombocytopénie très fréquemment observée chez les patients leucémiques s’accompagne dans la majorité des cas d’une élévation exponentielle de la concentration de thrombopoïétine, excepté dans les cas de leucémies de la lignée myéloïde. Chez ces derniers la concentration de thrombopoïétine est proche des valeurs observées chez des sujets normaux alors qu’elle devrait être 10 à 100 fois plus élevée compte tenu du nombre de plaquettes extrêmement bas. Nous avons pu montrer que ces taux très bas sont la conséquence de la liaison de la thrombopoïétine à un récepteur spécifique et fonctionnel présent à la surface des cellules leucémiques myéloïdes qui, en l’utilisant comme facteur de croissance, (stimulant leur prolifération et retardant leur mort cellulaire) « consomment » la thrombopoïétine présente dans le sérum.

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Con la finalidad de determinar los factores de riesgo de anemia en pacientes adultos mayores hospitalizados en los Servicios de Medicina del Hospital Arzobispo Loayza, se realizó un estudio explicativo, longitudinal, retrospectivo y prolectivo en una muestra representativa de 150 pacientes de la tercera edad 75 con anemia y 75 sin ella. Se encontraron como resultados que los factores de riesgo de anemia por enfermedad crónica en pacientes adultos mayores encontrados fueron la disfunción renal y el cáncer diagnosticado, por deficiencia de hierro fueron la presencia de angiodisplasia, cáncer y pólipos. Otros factores de riesgo de anemia estuvieron asociados al consumo reducido de Vit B12, la absorción intestinal reducida, la anorexia, y los trastornos del tránsito intestinal. La deficiencia de ácido fólico en la ingestión dietética inadecuada y la desnutrición también constituyeron factores de riesgo. El factor de riesgo de anemia por Síndromes mielodisplásicos en pacientes adultos mayores fue la presencia de hemorragias. Finalmente los factores demográficos como sexo y edad fueron dimensiones de riesgo de anemia en pacientes adultos mayores.

Thesis (M.A.)--University of Toronto, 2004. / Adviser: Thomas Humphries.

Thesis (M.S.)--University of Texas at Dallas, 2008. / Includes vita. Includes bibliographical references (leaf 22)

Thesis (M.S.)--California Polytechnic State University, 2008. / Mode of access: Internet. Title from PDF title page; viewed on April 20, 2009. Major professor: Susan Hawk, Ph.D., R.D. "Presented to the faculty of California Polytechnic State University, San Luis Obispo." "In partial fulfillment of the requirements for the degree of Master of Science in Agriculture, with Specialization in Food Science and Nutrition." "August 2008." Includes bibliographical references (p. 72-78). Also available on microfiche.

Thesis (Ph.D.)--University of Texas at Dallas, 2008. / Includes vita. Includes bibliographical references.