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Background: Red cell transfusions can lead to alloimmunization; however, pediatric alloimmunization frequency has not been well studied, and it may vary among diagnostic subgroups. Subgroups such as pediatric hematology/oncology patients require numerous transfusions during chemotherapy, but the immunosuppressive effect of chemotherapy on alloimmunization is unknown. One study demonstrated reduction in IgM and IgG in pediatric leukemia patients (Martín Ibáñez 2003); hence, one could hypothesize that chemotherapy suppresses alloimmunization. Objectives: This study aimed to: 1) describe alloimmunization frequency and antibody specificities in transfused pediatric patients; and 2) determine if chemotherapy affects the frequency of alloimmunization. Methods: A retrospective cohort study of pediatric patients (transfused between April 2002 and November 2011 at Hamilton Health Sciences) was performed. Data were extracted from 3 sources: a blood utilization database; the Laboratory Information System; and chart reviews. The chemotherapy treatment group included pediatric hematology/oncology patients stratified by HSCT status and diagnosis; control cohort included other pediatric patients not diagnosed with cancer. Control patients with hemoglobinopathies were analyzed separately due to increased alloimmunization. Alloimmunization was defined as clinically significant IgG alloantibody formation. Results: There were 1273 patients in the study: 949 in control group; 324 in study group. Alloimmunization was 1.6% overall: 0.6% (95% CI: 0, 1.47) in study group; 1.3% (95% CI: 0.58, 2.06) in control group. The association between chemotherapy and alloimmunization was not significant (p value = 0.38 Fisher’s exact test; OR 0.46, 95% CI: 0.10, 2.09). Due to low outcome rate, logistic regression to explore the association was not feasible. Conclusions: This is the first study exploring the frequency of alloimmunization in pediatric patients by diagnosis and the association between chemotherapy and alloimmunization. The frequency of alloimmunization was low and no association between chemotherapy and alloimmunization was observed. Low event rate would have contributed to low power. / Thesis / Master of Science (MSc)

La transfusion sanguine est un traitement essentiel à la survie de millions de patients. Son principal risque immunologique est l’allo-immunisation post-transfusionnelle. Elle se traduit par la production d’allo-anticorps contre des antigènes de globules rouges (GR) conduisant à des hémolyses post-transfusionnelles. Les mécanismes à l’origine de la tolérance des GR ou de son inhibition lors de l’allo-immunisation sont mal connus. Ainsi, mes travaux de thèse, portant sur la compréhension de ces effets, se sont articulés en trois parties avec 1/ l’étude des conditions optimales aux réponses allo-immunes, 2/ l’étude des effets d’une stratégie thérapeutique utilisant un anticorps monoclonal et 3/ l’étude des effets immunomodulateurs, incluant la tolérance, médiée par des composants présents dans les concentrés de globules rouges (CGR).Afin d’étudier l’allo-immunisation, nous avons utilisé le modèle murin. Nous montrons qu’une variation du délai entre la transfusion et la stimulation du TLR3 impacte la réponse immune dans la rate. Une activation importante des lymphocytes T CD4+ (LT CD4+) allo-réactifs accompagnée d’une production accrue d’allo-anticorps ont été montrées à 7 jours de délai. Afin de limiter l’allo-immunisation, l’utilisation d’un anticorps anti-CD20 déplétant les lymphocytes B (LB) montre une altération des LB mais surtout des LT CD4+ impliqués dans le processus d’induction de l’allo-immunisation. Enfin, la modification du phénotype des cellules dendritiques CD11c+ de la rate des souris transfusées, observée hors contexte inflammatoire, suggère une maturation incomplète à l’origine d’une tolérance antigénique. Pour finir, l’analyse de différents composants présents dans les CGR confirme l’existence de microparticules (MPs) lymphocytaires. Ces MPs présentent des molécules inhibitrices et pourraient donc être impliquées dans la tolérance des antigènes transfusés.En conclusion, mes travaux montrent la coopération des DCs avec les LT CD4+ permettant celle des LT CD4+ avec les LB pour induire une réponse immune. Comme toute réponse humorale, nous confirmons que l’allo-immunisation fait intervenir des DCs, des LT CD4+ et des LB. Ces résultats ouvrent de nouvelles voies de recherche pour mieux caractériser l’allo-immunisation en particulier chez les patients drépanocytaires qui sont les plus touchés. / Red blood cell (RBC) transfusion is a life-saving treatment for millions of patients. However, its main immunological risk is RBC alloimmunization resulting in antibody production against RBC antigen. Alloimmunization can lead to severe complications threatening the life of the patient. The mechanisms explaining RBC alloimmunization are poorly understood. Therefore, my doctoral work aiming at understanding transfusion effects, was subdivided into three parts with 1/ the study of optimal conditions for alloimmune responses, 2/ the impact of a therapeutic strategy using a monoclonal antibody to inhibit alloimmunization and 3/ the study of immunomodulatory effects of transfusion, including tolerance, through components present in the RBC concentrates.We also used HOD murine model for the study of alloimmunization to show an impact of the delay between the TLR3 agonist injection and the transfusion on immune responses against RBCs. At 7 days of delay, we have demonstrated an important alloreactive CD4+ T-cell activation and a wider alloantibody production. Furthermore, B-cell depletion, using a monoclonal anti-CD20 antibody, revealed potential changes on LB implicated in alloimmunization induction and mostly on alloreactive CD4+ T cells. We finally observed a modification of splenic CD11c+ DC phenotype from transfused mice out of a TLR context. This suggest an incomplete maturation that could explain antigen-specific tolerance. The investigation of several components in RBC concentrates confirmed the presence of microparticules (MPs) issued from T lymphocytes. These MPs carry inhibitory markers and could thus inhibit DC activation to induce antigen-specific tolerance.Therefore, my doctoral work highlights the implication and the cooperation of DCs with CD4+ T cells to allow cellular cooperation between CD4+ T cells and B cells for immune response induction. As in any humoral response, we confirmed that RBC alloimmunization involves DCs, CD4+ T cells and B cells. In addition, these results are opening up new areas of investigation for a better characterization of alloimmunization in particular in the most affected patients, the SCD patients.

Submitted by ALINE TROMBINI RODRIGUES null (aline.trombini.rodrigues@hotmail.com) on 2016-04-05T00:19:31Z No. of bitstreams: 1 Dissertação Aline Trombini Rodrigues.pdf: 2179862 bytes, checksum: 92ed01e81ff3781b11363c36b0c2268f (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-04-06T16:56:46Z (GMT) No. of bitstreams: 1 rodrigues_at_me_bot.pdf: 2179862 bytes, checksum: 92ed01e81ff3781b11363c36b0c2268f (MD5) / Made available in DSpace on 2016-04-06T16:56:46Z (GMT). No. of bitstreams: 1 rodrigues_at_me_bot.pdf: 2179862 bytes, checksum: 92ed01e81ff3781b11363c36b0c2268f (MD5) Previous issue date: 2016-02-24 / O conhecimento dos fenótipos eritrocitários de doadores de sangue é um procedimento essencial na prática transfusional, o qual aumenta a eficácia e a segurança do ato transfusional, além de prevenir a aloimunização. Os antígenos eritrocitários são clinicamente significantes na medicina transfusional, por serem altamente imunogênicos e pela possibilidade de causarem reações transfusionais, aloimunizações, anemias hemolíticas autoimunes e doença hemolítica do feto e recém-nascido (DHFRN). A incidência de aloimunização à antígenos eritrocitários é alta em pacientes politransfundidos, principalmente nos portadores de hemoglobinopatias e em pacientes submetidos a transplantes. O objetivo deste trabalho foi elaborar um banco de doadores de hemácias com diferentes fenótipos e painéis contendo soros e plasmas com anticorpos de importância clínica para atender e agilizar a transfusão de receptores de sangue alossensibilizados. Foi realizado um levantamento dos doadores de sangue do Hemocentro de Botucatu fenotipados utilizando registros de livros de bancada do ano de 2001 a 2007 e do sistema informatizado (Sistema de Banco de Sangue – SBS), através do qual encontramos um total de 6.039 doadores fenotipados, sendo que 2.700 tinham apenas registro nos livros de bancada. Das 31.942 amostras de doadores de sangue em que foram realizadas a Pesquisa de Anticorpos Irregulares (PAI) no período do nosso estudo, 77 apresentaram a PAI positiva na rotina laboratorial. Para a elaboração do Banco de Doadores Fenotipados, foram cadastrados e validados (duas ou mais fenotipagens realizadas) no sistema informatizado SBS, 7.074 antígenos de todos os sistemas de grupos sanguíneos. Desses, 4.748 (67,1%) antígenos pertenciam ao sistema Rh e 2.326 (32,9%) pertenciam a outros sistemas de grupos sanguíneos. Dos antígenos cadastrados (7.074), 2.396 (89%) antígenos não tinham nenhum histórico de fenotipagens anteriores e 304 (11%) já possuíam histórico e foram validados. De um total de 31.942 doadores de sangue, 77 apresentaram a PAI positiva. Para elaboração da soroteca/plasmateca constituída por painéis de soros/plasmas raros, realizamos novamente a PAI dessas amostras, seguida da Identificação de Anticorpos Irregulares (IAI), do tratamento com Dithiothreitol (DTT), se necessário, e da titulação de anticorpos. Destas 77 amostras de PAI positiva, 21 constituíram a soroteca/plasmateca, pois consideramos como critérios de inclusão: a importância clínica, a especificidade e o título dos anticorpos (reatividade com diluição maior que 1/2). Do total de anticorpos identificados (77), os de maior prevalência foram: anti-D, anti-E, anti-Dia, anti-M, anti-D+C e anti-Lea. Assim sendo, concluímos que é de suma importância a elaboração de um Banco de Doadores de Sangue com fenótipos menos frequentes, para que os pacientes em esquema de transfusão de concentrado de hemácias possam ser transfundidos de modo mais compatível possível, prevenindo deste assim a aloimunização a antígenos eritrocitários e otimizando a prática transfusional. É essencial também a elaboração de uma soroteca/plasmateca constituída de painéis de soros/plasma com anticorpos de importância clínica e, com isso, proporcionar além de uma maior agilidade na triagem da bolsa de concentrado de hemácias compatível, uma maior segurança para o paciente transfundido. / The knowledge of the erythrocyte phenotypes of blood donors is an essential procedure in transfusion practice, which increases the effectiveness and safety of transfusion Act, besides preventing the aloimunização. Erythrocyte antigens are clinically significant in transfusion medicine, because they are highly imunogênicos and the possibility of causing transfusional reactions, autoimmune hemolytic anemia, aloimunizações and hemolytic disease of the fetus and newborn (DHFRN). The incidence of alloimmunization to the erythrocyte antigens is high into politransfundidos patients, especially in patients with hemoglobinopathies and in patients undergoing organ transplants. The aim of this work was to develop a bank of red blood donors with different phenotypes and panels containing serums and plasmas with antibodies of clinical importance to attend and simplify the transfusion of blood alossensibilizados receivers. We manage a survey of blood donors from the Blood of Botucatu, using bench books records of the year 2001 to 2007 and computerised system (blood bank system SBS), through which we found a total of 6039 donors in conclusion, which only 2700 had records on the books. A total of samples (31942) of blood donors that were collected from the research of irregular antibodies (RAI) during the period of our study, 77 presented the RAI in laboratory routine. For the preparation of the donor bank in conclusion have been registered and validated (two or more fenotipagens made) in the computerised system SBS, 7074 antigens in every system of blood groups. Of these, 4748 (67.1) antigens belonged to the Rh system and 2326 (32.9) belonged to other blood group systems. Of registered antigens (7,074), 2396 (89) antigens had no history of previous fenotipagens and 304 (11) already had a history and have been validated. A total of 77 31942, blood donors showed the positive RAI. For the preparation of sorotecaplasmateca consisting of sorosplasmas rare panels carry out again the RAI of those samples, followed by the identification of irregular antibodies (IAI), treatment with Dithiothreitol (DTT) if necessary and titration of antibodies. Of these 77 samples were positive RAI, 21 formed the sorotecaplasmateca, because we believe as inclusion criteria: the clinical importance, the specificity and the title of antibodies (reactivity with dilution greater than 1/2). A total of identified antibodies (77), the most prevalent were: anti-D, anti-E, anti-Dia, anti-M, anti-D+C e anti-Lea . Therefore, we conclude that it is of the utmost importance to develop a Bank of blood donors with less frequent phenotypes, so that patients in transfusion of packed red blood cells, can be transfused as compatible as possible, preventing the alloimmunization to erythrocyte antigens and optimizing transfusion practice. It is essential also to draw up a sorotecaplasmateca consisting of sorosplasma panels with antibodies of clinical importance, for in this way we provide in addition to greater agility in the scholarship screening of packed cells compatible, greater safety for the patient transfused.

Made available in DSpace on 2014-06-11T19:23:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-20Bitstream added on 2014-06-13T20:29:57Z : No. of bitstreams: 1 felix_mc_me_botfm.pdf: 826136 bytes, checksum: 72fc2c810c332854ebb2731816d7b138 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação para o Desenvolvimento Médico e Hospitalar (Famesp) / As doenças crônico-degenerativas são caracterizadas por uma evolução lenta e progressiva, muitas vezes irreversível e por um longo período de latência. Resultam em alterações celulares que são importantes fatores de risco para a disfunção endotelial facilitando o desenvolvimento de úlceras venosas e/ou isquêmicas e “pé diabético”. O antígeno K do sistema eritrocitário Kell constitui um potente peptídeo bioativo com várias funções biológicas, dentre elas a vasoconstrição que influenciam diretamente nas doenças vasculares. As plaquetas, quando ativadas, liberam fatores de crescimento que aceleram o processo de cicatrização. Na membrana plaquetária são expressos antígenos como os eritrocitários, o polimórfico HLA-classe I e antígenos específicos das plaquetas (HPA), e alguns deles possuem importante significância clínica. O conhecimento e a compreensão dos fatores de crescimento existentes nas plaquetas levaram o setor de Biotecnologia do Hemocentro de Botucatu ao desenvolvimento de produtos que utilizam plaquetas e plasma homólogos excedentes da rotina transfusional como princípios ativos na composição de um gel empregado na forma de curativos com o objetivo de acelerar o processo de reparo tecidual. Sabendo os efeitos benéficos dos curativos bioativos no processo de cicatrização e da variabilidade genética dos antígenos plaquetários, qualquer situação em que ocorra exposição a esses antígenos poderia levar a uma resposta imune humoral. Diante dessa assertiva o presente estudo teve por finalidade avaliar o potencial imunogênico desses curativos em pacientes submetidos a essa terapêutica. Foi realizado um estudo multicêntrico, onde um total de 198 pacientes que receberam os curativos bioativos foram fenotipados para presença do antígeno Kell. Dentre esses pacientes, 100 foram selecionados para avaliar a relação dos antígenos... / The chronic-degenerative diseases are characterized by a slow and gradual evolution, often irreversible, and with a long period of latency. Resulting in cellular changes that are important risk factors for endothelial dysfunction facilitating the development of venous ulcers and/or ischemic and diabetic foot. The antigens of the erythrocyte Kell is a potent bioactive peptide with various biological functions among which vasoconstriction that directly influence the vascular diseases. Platelets, when activated, release growth factors that accelerate the healing process. Platelet membrane express antigens as the erythrocyte, the polymorphic HLA class I-specific antigens and of platelets (HPA), and some have important clinical significance. Knowledge and understanding of the growth factors present in platelets led the biotechnology sector from the Bloodbank of Botucatu to develop products using platelets and plasma counterparts surplus of routine transfusion as active ingredients in the composition of a gel used as a dressing with the objective to accelerate the process of tissue repair. Given the beneficial effects of bioactive dressings in the process of healing and the genetic variability of platelet antigens, a situation occurs where exposure to these antigens could lead to a immune response. Given this assertion this study was to evaluate the potential immunogenic effect of these dressings in patients undergoing such therapy. This was a multicenter study, where a total of 198 patients who received the bioactive dressings were phenotyped for the presence of Kell antigen. Among these patients, 100 were selected to assess the relationship of erythrocyte antigens of the ABO and Rh in the process of healing and alloimmunization anti-erythrocyte. Also, 38 were selected to evaluate the immunogenic potential of bioactive dressings through the search of anti-HLA and -HPA alloimmunization... (Complete abstract click electronic access below)

Orientador: Rosana Rossi Ferreira / Banca: Rejane Tommazini Grotto / Banca: Vânia Nieto Brito de Souza / Resumo: As doenças crônico-degenerativas são caracterizadas por uma evolução lenta e progressiva, muitas vezes irreversível e por um longo período de latência. Resultam em alterações celulares que são importantes fatores de risco para a disfunção endotelial facilitando o desenvolvimento de úlceras venosas e/ou isquêmicas e "pé diabético". O antígeno K do sistema eritrocitário Kell constitui um potente peptídeo bioativo com várias funções biológicas, dentre elas a vasoconstrição que influenciam diretamente nas doenças vasculares. As plaquetas, quando ativadas, liberam fatores de crescimento que aceleram o processo de cicatrização. Na membrana plaquetária são expressos antígenos como os eritrocitários, o polimórfico HLA-classe I e antígenos específicos das plaquetas (HPA), e alguns deles possuem importante significância clínica. O conhecimento e a compreensão dos fatores de crescimento existentes nas plaquetas levaram o setor de Biotecnologia do Hemocentro de Botucatu ao desenvolvimento de produtos que utilizam plaquetas e plasma homólogos excedentes da rotina transfusional como princípios ativos na composição de um gel empregado na forma de curativos com o objetivo de acelerar o processo de reparo tecidual. Sabendo os efeitos benéficos dos curativos bioativos no processo de cicatrização e da variabilidade genética dos antígenos plaquetários, qualquer situação em que ocorra exposição a esses antígenos poderia levar a uma resposta imune humoral. Diante dessa assertiva o presente estudo teve por finalidade avaliar o potencial imunogênico desses curativos em pacientes submetidos a essa terapêutica. Foi realizado um estudo multicêntrico, onde um total de 198 pacientes que receberam os curativos bioativos foram fenotipados para presença do antígeno Kell. Dentre esses pacientes, 100 foram selecionados para avaliar a relação dos antígenos... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The chronic-degenerative diseases are characterized by a slow and gradual evolution, often irreversible, and with a long period of latency. Resulting in cellular changes that are important risk factors for endothelial dysfunction facilitating the development of venous ulcers and/or ischemic and "diabetic foot." The antigens of the erythrocyte Kell is a potent bioactive peptide with various biological functions among which vasoconstriction that directly influence the vascular diseases. Platelets, when activated, release growth factors that accelerate the healing process. Platelet membrane express antigens as the erythrocyte, the polymorphic HLA class I-specific antigens and of platelets (HPA), and some have important clinical significance. Knowledge and understanding of the growth factors present in platelets led the biotechnology sector from the Bloodbank of Botucatu to develop products using platelets and plasma counterparts surplus of routine transfusion as active ingredients in the composition of a gel used as a dressing with the objective to accelerate the process of tissue repair. Given the beneficial effects of bioactive dressings in the process of healing and the genetic variability of platelet antigens, a situation occurs where exposure to these antigens could lead to a immune response. Given this assertion this study was to evaluate the potential immunogenic effect of these dressings in patients undergoing such therapy. This was a multicenter study, where a total of 198 patients who received the bioactive dressings were phenotyped for the presence of Kell antigen. Among these patients, 100 were selected to assess the relationship of erythrocyte antigens of the ABO and Rh in the process of healing and alloimmunization anti-erythrocyte. Also, 38 were selected to evaluate the immunogenic potential of bioactive dressings through the search of anti-HLA and -HPA alloimmunization... (Complete abstract click electronic access below) / Mestre

Orientador: Valéria Nogueira Dias Paes Secco / Resumo: O conhecimento dos fenótipos eritrocitários de doadores de sangue é um procedimento essencial na prática transfusional, o qual aumenta a eficácia e a segurança do ato transfusional, além de prevenir a aloimunização. Os antígenos eritrocitários são clinicamente significantes na medicina transfusional, por serem altamente imunogênicos e pela possibilidade de causarem reações transfusionais, aloimunizações, anemias hemolíticas autoimunes e doença hemolítica do feto e recém-nascido (DHFRN). A incidência de aloimunização à antígenos eritrocitários é alta em pacientes politransfundidos, principalmente nos portadores de hemoglobinopatias e em pacientes submetidos a transplantes. O objetivo deste trabalho foi elaborar um banco de doadores de hemácias com diferentes fenótipos e painéis contendo soros e plasmas com anticorpos de importância clínica para atender e agilizar a transfusão de receptores de sangue alossensibilizados. Foi realizado um levantamento dos doadores de sangue do Hemocentro de Botucatu fenotipados utilizando registros de livros de bancada do ano de 2001 a 2007 e do sistema informatizado (Sistema de Banco de Sangue – SBS), através do qual encontramos um total de 6.039 doadores fenotipados, sendo que 2.700 tinham apenas registro nos livros de bancada. Das 31.942 amostras de doadores de sangue em que foram realizadas a Pesquisa de Anticorpos Irregulares (PAI) no período do nosso estudo, 77 apresentaram a PAI positiva na rotina laboratorial. Para a elaboração do Banco d... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The knowledge of the erythrocyte phenotypes of blood donors is an essential procedure in transfusion practice, which increases the effectiveness and safety of transfusion Act, besides preventing the aloimunização. Erythrocyte antigens are clinically significant in transfusion medicine, because they are highly imunogênicos and the possibility of causing transfusional reactions, autoimmune hemolytic anemia, aloimunizações and hemolytic disease of the fetus and newborn (DHFRN). The incidence of alloimmunization to the erythrocyte antigens is high into politransfundidos patients, especially in patients with hemoglobinopathies and in patients undergoing organ transplants. The aim of this work was to develop a bank of red blood donors with different phenotypes and panels containing serums and plasmas with antibodies of clinical importance to attend and simplify the transfusion of blood alossensibilizados receivers. We manage a survey of blood donors from the Blood of Botucatu, using bench books records of the year 2001 to 2007 and computerised system (blood bank system SBS), through which we found a total of 6039 donors in conclusion, which only 2700 had records on the books. A total of samples (31942) of blood donors that were collected from the research of irregular antibodies (RAI) during the period of our study, 77 presented the RAI in laboratory routine. For the preparation of the donor bank in conclusion have been registered and validated (two or more fenotipagens made) in th... (Complete abstract click electronic access below) / Mestre

Made available in DSpace on 2015-04-11T13:38:35Z (GMT). No. of bitstreams: 1 Dissertacao Francimary.pdf: 640225 bytes, checksum: 1eebacf1e67b120750607e8d1a1c46d2 (MD5) Previous issue date: 2005-10-26 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / The presence of G class irregular erythrocyte alloantibodies in the blood circulation during pregnancy may cause a series of consequences to the newborn. The alloimmunization can occur under different situations, such as: blood incompatibility during delivery, miscarriage, amniocentese, blood transfusion, among others, all considered being risky. This study investigated the occurrence of regular and irregular circulating alloantibodies in women under the care of the Program of RhD-negative Expecting Mothers (PGRhN) of the Amazonas Hematology and Hemotherapy Foundation (HEMOAM). A retrospective study was carried out compiling the data of all expecting mothers under care during 2003, as well as the information regarding their newborns. A second study, prospective, was done by analyzing the blood samples of expecting mothers under the care of the PGRhN between April and November 2004, as well as the information on their respective babies. All tests were carried out following the methodology presented in the American Association of Blood Bank Technical Manual (2005). The comparison of the alloimmunization frequency between the first (5.6%) and the second (3.5%) studies showed no significant difference. The frequency of antibodies attached to the erythrocytes in the newborns of alloimmunized mothers were high, 67% in the retrospective study and 72.7% in the prospective study. The frequency of G class regular alloantibodies was 87% in the prospective study and the ABO maternal-fetal incompatibility was 17% in O type mothers with A or B type progeny. The occurrence of irregular alloimmunization in the PGRhN is still high, comparing with the numbers of other authors, indicating that the Program may be failing in preventing the problem to occur or errors may have been made during the sorotherapy of patients under risk. Also, it was observed a high frequency of G class regular alloantibodies which can cause the Hemolytic Disease of the Newborn (HDN) due to ABO incompatibility. / A presença de aloanticorpos irregulares eritrocitários da classe G, na circulação materna, pode causar serias conseqüências ao neonato. A aloimunizacao pode ocorrer em diversas situações, consideradas de risco, como partos com incompatibilidade sanguínea, aborto, amniocentese, transfusões sanguínea, dentre outras. Neste estudo foi verificada a presença de aloanticorpos circulantes regulares e irregulares, em mulheres atendidas no Programa de Gestantes Rh Negativo (PGRhN) da Fundação de Hematologia e Hemoterapia do Amazonas (HEMOAM). Foi realizado um estudo retrospectivo e para o qual, foram levantados os registros de gestantes atendidas durante o ano de 2003, como também, os dados de seus recém-nascidos. Outro estudo, prospectivo, foi realizado e foram analisadas amostras de sangue de gestantes, atendidas no PGRhN entre os meses de abril a novembro de 2004, como também de seus recém-nascidos. Todos os testes utilizados foram preconizados pelo Manual Técnico da American Association of Blood Bank (2005). A freqüência de aloimunizacao no estudo Retrospectivo (5,6%) não apresentou diferença significante com a do estudo Prospectivo (3,5%). A freqüência de anticorpos fixados as hemácias, nos recém-nascidos de mães aloimunizadas, foi bastante alta, de 67% no estudo prospectivo e de 72,7% no estudo retrospectivo. A freqüência de aloanticorpos regulares da classe G foi de 87% nas gestantes do estudo prospectivo e a incompatibilidade ABO materno-fetal foi de 17% para as mães O, com filhos A ou B. O índice de aloimunização irregular no PGRhN ainda e muito alto, quando comparado aos trabalhos de outros autores, mostrando que devem estar ocorrendo falhas na prevenção e possíveis erros na administração da soroterapia, em situações de risco. Ressalte-se ainda, a alta freqüência de aloanticorpos regulares da classe G, que podem induzir a Doença Hemolítica do recém-nascido (DHRN) por incompatibilidade ABO.

Made available in DSpace on 2014-02-26T19:13:30Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 56122.pdf: 943164 bytes, checksum: 31ab7a412fa0e24ec2743d0b364e47f6 (MD5) Previous issue date: 2013-07-22 / Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Ensino. Programa de Pós-Graduação em Saúde da Criança e da Mulher. Rio de Janeiro, RJ, Brasil. / Introdução: a Doença Hemolítica Perinatal pelo fator Rh é causada pela incompatibilidade entre o sangue da mãe e do recém-nascido, levando a destruição de hemácias fetais e, sem tratamento os fetos mais severamente afetados podem morrer intra-útero. No recém-nascido, a doença pode resultar em icterícia,anemia, dano cerebral, falência cardíaca e morte.Desde introdução da profilaxia anti-Rh D o número de recém-nascidos com doença hemolítica tem caído drasticamente em países desenvolvidos, porém essa não é a realidade nacional. Objetivo Geral:descrever as práticas usadas para tratar os pacientes com doença hemolítica perinatal pelo fator Rh, nascidos no Instituto Fernandes Figueira nos últimos 10 anos e apresentar dados clínicos,laboratoriais, o tipo de abordagem terapêutica oferecida e o perfil imunohematológico de suas mães. Material e métodos:Foi realizada uma cohort de 300 recém-nascidos de gestantes Aloimunizadas Rh, nascidos no Instituto Fernandes Figueira no período de janeiro de1995 a dezembro de 2004. Foram coletados dados do pré-natal,nascimento e acompanhamento do Follow-up até 1 ano de idade. Resultados: a maioria de nossas gestantes possuía um anticorpo que foi o anti-D, sendo que a gravidade da doença hemolítica não teve relação com o tipo de anticorpo. O início do pré-natal em nossa unidade é tardio, mas mesmo assim a maioria dos recém-nascidos nasce bem. Nosso índice de óbitos e hidropisialmente está em torno de 7%. Foi evidenciada uma queda de 66 para 35,8% do número de pacientes submetidos à exsangüineotransfusão após o ano 2000 coincidindo com a introdução biliberço e uso da imunoglobulina humana inespecífica, sem comprometimento do prognóstico. Nosso índice de mortalidade relacionado à exsangüineotransfusão foi de 0,7% e de eventos adversos foi de 61%, sendo os mais comuns a plaquetopenia (mais ou menos 50.000) e distúrbios hidroeletrolíticos (hipocalcemia).Os eventos mais graves foram os distúrbios cardiológicos e de sangramento foram estatisticamente maiores nos pacientes cujas condições clínicas eram mais instáveis antes do procedimento. Fatores como níveis críticos de bilirrubina(mais ou menos 20 mg/dl), a prematuridade, hidropisia e asfixia pioram o prognóstico tardio (surdez e encefalopatia bilirrubínica)apesar de intervenção terapêutica precoce. Conclusões: Novas terapias têm sido desenvolvidas para abordagem do recém-nascido com Doença Hemolítica Perinatal como as fototerapias de alta intensidade e a imunoglobulina humana inespecífica, levando a uma diminuição no uso da exsangüineotransfusão, porém esta ainda é uma técnica usada em casos graves de hiperbilirrubinemia.Vários eventos adversos são descritos em conseqüência deste procedimento e são na maioria das vezes assintomáticos e passiveis de correção, mas não podemos deixar de levar em consideração a gravidade do recém-nascido antes do procedimento,além da experiência clínica do profissional que realizará o procedimento. Apesar da intervenção terapêutica precoce os pacientes com fatores de risco(Bt máx mais ou menos 20mg/dl,asfixia,hipoproteinemia e prematuridade) tiveram um prognóstico neurológico pior. / Introduction: The hemolytic disease secondary to rhesus alloimmunization is caused by the incompatib ility between the mother's and the newborn’s blood, leading to the destruction of fetal r ed blood cells and without treatment the fetuses more severely affected can di e intra-uterus. Afte r the delivery the newborn’s disease can result in j aundice, anemia, cerebral damage, heart failure and death. Since the introducti on of the prophylaxis anti-Rh D the number of newborn with hemolytic dis ease has been falling drastically in developed countries, however that is not the Brazilian reality. Objective : Describe the practices used to tr eat the patients with the hemolytic disease secondary to rhesus alloimmunizati on, who were born at IFF in the last 10 years. Describing clinical data, lab abnormalities, therapeutic approach and immunohematologic characteristic of their mothers. Material and methods: Its was done a cohort of 300 newborns of pregnant women’s with alloimmunization by Rh ant ibody, with babies Instituto Fernandes Figueira in the period of January 1995 to December 2004. The program EPI 6 made the statistical analyses. Results: The mostly found antibody in the pregnant women was the anti-D, and the severity of the hemolytic diseas e didn't have relationship with the types of antibodies. The beginning of the prenatal in our unit is late, but even so most are healthy. Deaths or hydrops ar e around 7%. It was evidenced a newborns fall of 50% in patients undergoing the exchange transfusion after the year 2000, coinciding with the introduction of the Biliberço® and use of the intravenous immunoglobulin, without affecting their prognos tic. Our mortality rate related to the exchange transfusion was of 0,7% and the one related to adverse events was of 61% , being the most co mmon thrombocytopenia (< 50.000) and hypocalcemia. The most serious events were bradycardia or heart arrhythmia and bleeding. These disturbances were mo re prevalent in the patients whose clinical conditions were unstable bef ore exchange transfusion. Factors as critical levels of bilirubin ( ≥ 20 mg/dl), prematurity, hydrops fetalis and asphyxia, worsen the neurological prognostic (deafness and bilirubin encephalopathy). Conclusions: New therapies have been developed for the approach of the newborns with hemolytic disease as the phototherapy of high intensity and the intravenous immunoglobulin, leading to a dec rease in the use of the exchange transfusions, but this is still a saving life technique in the serious cases of hiperbilirrubinemia. Several adverse ev ents are described as a consequence of this procedure and most of the ti me they show no symptoms and are susceptible to correction, but we have consider the severity of the patient’s clinical conditions and the professional's skill. Besides the early therapeutic intervention in patients with risk factors (BT máx ≥ 20 mg/dl, the preterm infants, hydrops fetalis and asphyxia) it had a worse neurological prognostic.

HPA1a är ett antigen på trombocytytan som kan orsaka alloimmunisering, såsom neonatal alloimmun trombocytopeni och post-transfusion purpura, vilket kan ge svåra blödningssymptom. I fall med antikroppar mot HPA1a måste kompatibla trombocyter finnas tillgängliga. Syftet med studien var att etablera en flödescytometrisk screeningmetod för fenotypning av HPA1a antigen på trombocyter samt att finna HPA1a negativa blodgivare. Före flödescytometrisk analys poolades två till fem blodprover samman till ett prov och vid förekomst av HPA1a negativa trombocyter i poolen analyserades proverna individuellt. Fluorokrommärkta anti-humana antikroppar mot CD42a och CD61 användes för att särskilja HPA1a negativa trombocyter från HPA1a positiva. Totalt fenotypades 177 blodprover varav sju (4%) typades som HPA1a negativa. Av de sju fynden genotypades fyra vid ett externt laboratorium vilket bekräftade att de var HPA1a negativa. Flödescytometrisk screening av HPA1a är snabb, pålitlig och lämplig för storskalig screening. För att fastställa prevalensen av HPA1a negativa individer behöver mer omfattande studier utföras där en större population ingår. Att ha flera HPA1a negativa blodgivare registrerade ger möjligheten att hjälpa patienter i andra regioner. / HPA1a is an antigen on the platelet surface that can cause alloimmunization, such as neonatal alloimmune thrombocytopenia and post transfusion purpura, which can cause severe bleeding symptoms. In case of antibodies against HPA1a, compatible platelets must be available. The purpose of the study was to establish a flow cytometric screening method for phenotyping HPA1a antigen on platelets and to find HPA1a negative donors. Before the flow cytometric analysis, two to five blood samples were pooled into one sample and in the presence of HPA1a negative platelets in the pool, the samples were analyzed individually. Fluorochrome –labeled anti-human antibodies to CD42a and CD61 were used to distinguish HPA1a negative platelets from HPA1a positive. A total of 177 blood samples were phenotyped, of which 7 (4%) were HPA1a negative. Of the seven findings, four samples were genotyped at an external laboratory confirming that they were HPA1a negative. Flow cytometric screening of HPA1a is fast, reliable and suitable for large scale screening. In order to determine the prevalence of HPA1a negative individuals, more extensive studies need to be performed involving a larger population. By having many registered HPA1a negative donors, it can provide opportunities to help patients in other regions.