A transfusão de sangue é um procedimento benéfico, mas não isento de risco, e por essa razão medidas devem ser tomadas para aumentar a sua segurança, entre elas a adoção de boas práticas transfusionais e as notificações dos eventos adversos, que compõe as atividades de hemovigilância. O objetivo do estudo foi avaliar o impacto da implantação de uma equipe transfusional e da busca ativa por reações transfusionais nas atividades de hemovigilância e na segurança transfusional em um Núcleo de Hemoterapia regional, localizado em um hospital geral. Foi realizado um estudo comparativo entre dois períodos: antes e após a implantação da equipe transfusional. Observou-se um aumento de 9,04 vezes no número de notificações de reações transfusionais, elevando de duas notificações em 1.677 transfusões realizadas (0,12%) no período de 22 meses antes da implantação, para dez notificações em 928 transfusões (1,08%, p<0,01) no período de 12 meses após, revertendo a subnotificação existente. As RFNH foram as reações transfusionais mais frequentemente encontradas, havendo aumento significativo nas notificações, de uma RFNH antes para seis após a implantação da equipe transfusional (p<0,01). Observou-se também um aumento na segurança transfusional, corrigindo falhas na identificação de amostras e requisições de transfusão, na verificação dos sinais vitais e identificação dos pacientes, minimizando assim o risco de reações graves por troca de amostras/pacientes. O estudo mostrou que ter um profissional acompanhando o ato transfusional desde a coleta da amostra até o término da transfusão, traz mais segurança para o receptor da transfusão, ao permitir que os procedimentos estabelecidos sejam seguidos, e aumenta as notificações de eventos adversos, favorecendo o reconhecimento das reações transfusionais e fornecendo subsídios para a adoção de estratégias para sua prevenção e tratamento. Ao final do estudo foram elaborados cartazes e panfletos para orientação de profissionais e pacientes, respectivamente, sobre a transfusão de sangue. / Blood transfusion can be unavoidable and beneficial but has inherent risks. Hemovigilance actions, therefore, should be undertaken to increase its safety, including the adoption of better blood transfusion initiatives and adverse event reporting. The purpose of this study was to evaluate how the introduction of a transfusion practitioner team to monitor transfusion outcomes affects the hemovigilance system and the transfusion safety in a regional hemotherapy center based in a general hospital. We performed a comparison of two clinical periods: before and after the introduction of a transfusion practitioner team. An increase was observed from 2 event reports in 1677 transfusions (0.12%) in a 22-month period to 10 event reports in 928 transfusions (1.08%, p<0.01) in a 12-month period, demonstrating a 9.04-fold increase in transfusion reaction reports, drastically reducing the frequency of underreporting. Febrile non-hemolytic reactions were the most frequent adverse event reported, with a significant increase from 1 to 6 events reported (p <0.01) after the involvement of the transfusion team. There was also an improvement in transfusion safety practices via the correction of misidentification of patient pretransfusion samples and transfusion requests, the avoidance of failure to verify vital signs, and improvement of patient identification at the bedside, all of which are critical to minimize the risk of transfusion error. The study showed that having a professional team oversee the transfusion process, from sample collection to blood administration, brings more safety to the patient by allowing established procedures to be followed. The adoption of this practice increases reporting of adverse events through the early recognition of transfusion reactions, expediting their treatment and enhancing the prevention of future events. At the end of the study posters and educational packets were created to provide guidance about blood transfusion to leading professionals and patients.

A transfusão de sangue é um procedimento benéfico, mas não isento de risco, e por essa razão medidas devem ser tomadas para aumentar a sua segurança, entre elas a adoção de boas práticas transfusionais e as notificações dos eventos adversos, que compõe as atividades de hemovigilância. O objetivo do estudo foi avaliar o impacto da implantação de uma equipe transfusional e da busca ativa por reações transfusionais nas atividades de hemovigilância e na segurança transfusional em um Núcleo de Hemoterapia regional, localizado em um hospital geral. Foi realizado um estudo comparativo entre dois períodos: antes e após a implantação da equipe transfusional. Observou-se um aumento de 9,04 vezes no número de notificações de reações transfusionais, elevando de duas notificações em 1.677 transfusões realizadas (0,12%) no período de 22 meses antes da implantação, para dez notificações em 928 transfusões (1,08%, p<0,01) no período de 12 meses após, revertendo a subnotificação existente. As RFNH foram as reações transfusionais mais frequentemente encontradas, havendo aumento significativo nas notificações, de uma RFNH antes para seis após a implantação da equipe transfusional (p<0,01). Observou-se também um aumento na segurança transfusional, corrigindo falhas na identificação de amostras e requisições de transfusão, na verificação dos sinais vitais e identificação dos pacientes, minimizando assim o risco de reações graves por troca de amostras/pacientes. O estudo mostrou que ter um profissional acompanhando o ato transfusional desde a coleta da amostra até o término da transfusão, traz mais segurança para o receptor da transfusão, ao permitir que os procedimentos estabelecidos sejam seguidos, e aumenta as notificações de eventos adversos, favorecendo o reconhecimento das reações transfusionais e fornecendo subsídios para a adoção de estratégias para sua prevenção e tratamento. Ao final do estudo foram elaborados cartazes e panfletos para orientação de profissionais e pacientes, respectivamente, sobre a transfusão de sangue. / Blood transfusion can be unavoidable and beneficial but has inherent risks. Hemovigilance actions, therefore, should be undertaken to increase its safety, including the adoption of better blood transfusion initiatives and adverse event reporting. The purpose of this study was to evaluate how the introduction of a transfusion practitioner team to monitor transfusion outcomes affects the hemovigilance system and the transfusion safety in a regional hemotherapy center based in a general hospital. We performed a comparison of two clinical periods: before and after the introduction of a transfusion practitioner team. An increase was observed from 2 event reports in 1677 transfusions (0.12%) in a 22-month period to 10 event reports in 928 transfusions (1.08%, p<0.01) in a 12-month period, demonstrating a 9.04-fold increase in transfusion reaction reports, drastically reducing the frequency of underreporting. Febrile non-hemolytic reactions were the most frequent adverse event reported, with a significant increase from 1 to 6 events reported (p <0.01) after the involvement of the transfusion team. There was also an improvement in transfusion safety practices via the correction of misidentification of patient pretransfusion samples and transfusion requests, the avoidance of failure to verify vital signs, and improvement of patient identification at the bedside, all of which are critical to minimize the risk of transfusion error. The study showed that having a professional team oversee the transfusion process, from sample collection to blood administration, brings more safety to the patient by allowing established procedures to be followed. The adoption of this practice increases reporting of adverse events through the early recognition of transfusion reactions, expediting their treatment and enhancing the prevention of future events. At the end of the study posters and educational packets were created to provide guidance about blood transfusion to leading professionals and patients.

Le virus de l’hépatite E (VHE) est l’agent causal d’une partie des hépatites aigues ou fulminantes qui surviennent essentiellement dans les pays en voie de développement (Afrique, Asie) ou le VHE de génotype 1 semble présenter un profil endémique ponctué de bouffées épidémiques souvent liées à des déplacements de populations (catastrophe climatique ou conflits) (Lui et al., 2013). Récemment il a été montré que ce virus était largement distribué dans des réservoirs animaux (génotype 3 et 4) et la cause d’un grand nombre d’infections zoonotiques aussi bien dans les pays du nord que du sud. Dans la plupart des cas, il s'agit d'une infection spontanément résolutive avec une clairance virale rapide, mais il peut évoluer vers des formes plus sévères avec un niveau de mortalité variant de 1 à 4% dans la population générale et à près de 20% chez la femme enceinte lors des flambées épidémiques (OMS, 2014). Au Burkina Faso, très peu de données existent sur la prévalence chez l’homme, l'épidémiologie moléculaire du VHE ou la présence de ce virus dans le réservoir animal principal que constituent les porcs. De plus, l’ignorance de la population quant aux causes de cette infection d’origine alimentaire, est un facteur de risque qu’on ne peut pas ignorer. L’objectif de ce travail est donc d’améliorer notre connaissance sur cet agent des hépatites. La première partie de notre étude s’est consacrée à l’évaluation de la séroprévalence du VHE chez les donneurs de sang et les femmes venant en consultation prénatale à Ouagadougou. Au total plus de 1700 échantillons de sérums de volontaires ont été collectés dans les banques de sang et centres médicaux: entre 2010 et 2012, sur les 178 donneurs de sang et 189 femmes enceintes testés, 19,1% [IC95, 13,3-24,9%] et 11,6% [IC95, 7,1-16,2%] étaient respectivement positifs aux IgG anti-VHE. Ces taux élevés sont peut-être associé au faible statut socioéconomique et à l’absence de réseaux d’assainissement des eaux (Traoré et al., 2012). En 2014, 3,19% [IC95, 1,70-4,68%] des 533 donneurs de sang testé sont positifs pour des IgM anti-VHE. Ces résultats montrent un risque résiduel transfusionnel non négligeable associé à une transmission à bas bruit et confirme l’intérêt d’identifier la ou les sources de ce virus. La seconde partie de ce travail a été de vérifier le rôle d’une source zoonotique des infections à VHE, via l’évaluation du VHE (par sérologie et typage moléculaire après PCR) dans le réservoir potentiel que sont les porcs et la population à risques exposé à ce réservoir (bouchers et éleveurs). Pour cela nous avons réalisé un recensement des sites de ventes de porcs et évalué la consommation d’animaux. Un taux de séroprévalence de 76% [IC95, 67,6-84,4%] a été mesuré dans une cohorte de 100 bouchers de Ouagadougou avec un facteur de risque de séropositivité 3 fois plus élevé par rapport à la population générale (OR = 3,46 [95%CI 2,85 – 4,21] p <0.001). Les IgG anti-VHE chez les porcs abattus ont été estimés à 80% IC95 [72-87%]. Cette forte prévalence confirme une circulation silencieuse du VHE dans l’élevage porcin au Burkina Faso comme en témoigne l'échantillon positif de foie pour l’ARN VHE qui soutient fermement le risque de zoonose. L’analyse des séquences des produits de PCR des foies de porcs positifs pour VHE a révélé la présence de VHE génotype 3 et 99,8 % d'homologie avec les souches Yaounde et Madagascar. En conclusion, notre étude, la première caractérisation moléculaire des souches du VHE au Burkina, montre la présence de souches VHE génotype 3 dans des régions ou seul le génotype 1 avait été identifié jusqu’alors (Tchad, Maroc). L’évaluation du risque transfusionnel associé nécessite des études complémentaires afin d’évaluer le bénéfice/coût de l'ajout de dépistage du VHE dans les examens de routines des banques de sang, afin de garantir la sécurité du receveur de sang. / The hepatitis E virus (HEV) is causative agent several acute or fulminant hepatitis which mainly occur in developing countries where HEV genotype 1 or 2 appears to have a endemic profile punctuated with epidemic outbreaks (Africa, Asia) (Lui et al., 2013). Genotype 3 and 4 distributed widely in animal reservoirs, were the cause many zoonotic infection in northern and southern countries. In most cases, it is a self-limited infection with rapid viral clearance, but it can evolve into more severe forms with a mortality level ranging from 1 to 4% in the general population to nearly 20% in pregnancy during outbreaks (WHO, 2014). In Burkina Faso, very little epidemiological data are available on HEV. The objective of this work is to improve our understanding of this agent hepatitis. The first part of our study was devoted to the evaluation HEV seroprevalence among blood donors and women attending antenatal care in Ouagadougou. In total more than 1,700 volunteers serum samples were collected in blood banks and medical centers in Burkina Faso. Between 2010 and 2012 on 178 blood donors and 189 pregnant women tested, 19.1% [CI95, 13.3-24.9%] and 11.6% [CI95, 7.1-16.2%], were respectively positive for anti-HEV IgG. These high rates in the general population may be associated a low income and the poor hygienic status (Traoré et al., 2012). In 2014, 3.19% [CI95, 1.70-4.68%] on 525 blood donors tested, were positive for anti-HEV IgM. These results indicate a residual risk for transfusion, probably associated with silent infections and confirm the importance to identify the sources of the virus. The second part of this work was 1) to assess HEV infection among humans in Burkina Faso by exploring the HEV seroprevalence in a high risk population, i.e., butchers; 2) to explore a possible pig-to-human zoonotic transmission cycle by assessing the HEV seroprevalence in slaughter swine; and 3) to identify the genotype of HEV circulating in pigs. The global HEV prevalence among Ouagadougou butchers was estimated to 76%, CI95 [67, 63–84.37%] with a significant risk factor, 3 times higher compared with the general population (OR = 3.46 [95%CI 2.85 - 4.21] p <0.001). IgG anti-HEV in pigs older than 6 months of age were estimated at 80% CI95 [72-87%]. This high prevalence confirms the presence and active circulation HEV among domestic pigs in Burkina Faso as evidenced by the positive sample of liver for HEV RNA which strongly supports the risk of zoonosis. Phylogenetic analyses revealed that genotype 3 HEV is circulating among swine population in Burkina. A similarity >98% was found between swHEV-BF from Yaounde and Madagascar. This data showed for the first time the role of swine in introduction of new HEV in African population. In conclusion, these results latter sign a persistent introduction of HEV infection in the population and hence deserved to be taken in account in transfusion associated risk. Further assessments of the transfusion risk associated require an evaluation of the cost/benefit ratio for the addition of routine HEV RNA screening to the panel of tests on donated blood, to guarantee transfusion safety for the recipient.

La transfusion sanguine est une thérapeutique indispensable pour laquelle il n’existe pas actuellement de substitut. La transfusion de produits sanguins labiles est dans la grande majorité des cas très bien tolérée mais elle peut être à l’origine d’effets indésirables chez les receveurs (EIR) notamment de type inflammatoire. Ceci dépend de facteurs liés aux produits eux-mêmes et/ou aux receveurs de par leur prédisposition génétique et de leur état clinique. Les concentrés plaquettaires (CP) sont la principale source de manifestations inflammatoires et/ou allergiques. Ceci est notamment dû, en partie, à la capacité des plaquettes à sécréter une multitude de molécules ayant une activité inflammatoire. De plus, les processus de collecte, de préparation et de conservation induisent un stress vis-à-vis des cellules, qui peut activer les plaquettes et donc induire la production de produits inflammatoires dans les CP. Le but de ce travail de thèse a été dans un premier temps d’identifier les molécules les plus impliquées dans les manifestations inflammatoires. Le sCD40L en particulier est identifié comme étant largement impliqué dans les EIR après transfusion de CP, mais pas systématiquement. Aussi, la composante inflammatoire de ces réactions est multifactorielle. De plus, nous avons évalué le potentiel inflammatoire des CP sur l’endothélium vasculaire. Des différences d’activation des cellules endothéliales, dans un modèle in vitro, ont été observées lorsqu’elles sont en présence de surnageants de CP ayant induits un EIR. Ce travail de thèse poursuit l’effort entrepris par notre équipe de recherche, en vue de prédire la survenue d’EIR et de préciser les mécanismes qui influencent la physiopathologie plaquettaire transfusionnelle ; un corollaire de ces travaux est ainsi d’optimiser les processus de production et de conditionnement des CP transfusés afin de réduire ces réactions inflammatoires. / Blood transfusion is an indispensable therapy for which there is currently no substitute. Transfusion of blood products is in the great majority of cases very well tolerated but it can be at the origin of serious adverse reactions (SARs), notably of inflammatory reactions. This depends on the factors related to the products themselves and/or to the recipients, their genetic predisposition and clinical condition. Platelet concentrates (PCs) are the main source of inflammatory and/or allergic manifestations. This is due, in part, to the ability of platelets to secrete a multitude of molecules with inflammatory activity. In addition, the collection, processing and storage conditions induce stress on cells, which can activate platelets and thus induce the production of inflammatory products in PCs. The purpose of this work is to identify the molecules involved in inflammatory manifestations. sCD40L was identified as being involved in SARs after PCs transfusion, but not systematically. Also, the inflammatory component of these reactions is multifactorial. In addition, we evaluated the inflammatory potential of PCs on the vascular endothelium. Differences in endothelial cell activation, in an in vitro model, were observed when they were in the presence of PC supernatants involved in SARs. This thesis work continues the effort undertaken by our research team to predict the occurrence of SARs and to clarify the mechanisms that influence transfusional platelet physiopathology; a corollary of this work is to optimize the production and conditioning process of PCs transfused in order to reduce these inflammatory reactions.

La transplantation hépatique (TH) est une intervention à risque hémorragique, au cours de laquelle toutes les étapes de la coagulation (hémostase primaire, hémostase secondaire, fibrinolyse) sont perturbées. Nous avons d’abord montré que les facteurs de risque de saignement et transfusion étaient difficiles à identifier et n’étaient pas cliniquement très pertinents. Puis nous avons montré que la thromboélastométrie (ROTEM®) pouvait diagnostiquer la thrombopénie et l’hypofibrinogénémie au cours de la TH, même si l’utilisation d’un algorithme basé sur le ROTEM® ne diminuait pas le saignement ni la transfusion par rapport à un algorithme basé sur les résultats du laboratoire. De plus le ROTEM® manquait de sensibilité pour détecter l’hyperfibrinolyse. La thrombine est l’enzyme-clé de la cascade de la coagulation. Le Calibrated Automated Thrombogram (CAT®) est la méthode de référence de génération de thrombine. Nous avons cherché des moyens rapides d’évaluation de la génération de thrombine, utilisable en routine et sur échantillons individuels. Le Thrombodynamics-4D® (TD4D) permettait à la fois l’étude de la formation et de la propagation du caillot de fibrine dans le temps et l’espace et de la génération de thrombine. Une hyperfibrinolyse survient au cours de 20 à 66% des TH. Elle majore le saignement et la transfusion. Le diagnostic rapide de l’hyperfibrinolyse permettrait un traitement rapide et ciblé par antifibrinolytique. Le Lysis Timer était plus sensible que le ROTEM® pour détecter les hyperfibrinolyses. Le TD4D permettait également de visualiser la lyse du caillot. L’utilisation en routine de ces nouveaux appareils nécessite la validation des résultats sur plasma frais, après accélération des étapes pré-analytiques (centrifugation rapide) et des études cliniques pour les positionner au sein d’algorithmes transfusionnels. / Liver transplantation (LT) is a bleeding procedure, in which all the haemostatic steps (primary haemostasis, secondary haemostasis, fibrinolysis) are impaired. We have first shown the predictive factors of bleeding and transfusion were difficult to determine and were of poor clinical relevance. Then, we showed that thromboelastometry (ROTEM®) could detect thrombocytopenia and hypofibrinogenemia during LT. However, the utilisation of an algorithm based on ROTEM® results did not led to less bleeding and transfusion when compared to an algorithm based on laboratory results. Moreover, ROTEM® lacked sensitivity to detect hyperfibrinolysis. Thrombin is the key-enzyme of coagulation cascade. The Calibrated Automated Thrombogram (CAT®) is the reference test for thrombin generation. We searched for rapid tools to evaluate thrombin generation, usable in routine and on individual plasma samples. The Thrombodynamics-4D® (TD4D) enabled in the same time study of fibrin clot formation and propagation in time and space and thrombin generation. Hyperfibrinolysis is encountered in 20 to 66% of LT procedures. It is associated with more bleeding and transfusion. Rapid diagnosis of hyperfibrinolysis would allow a quick and target treatment with antifibrinolytic drugs. Lysis Timer was more sensitive than ROTEM® to detect hyperfibrinolysis. TD4D also visualized clot lysis. Routine utilization of these new devices now requires validation of its results in fresh plasma, after acceleration of pre-analytic steps (rapid centrifugation) and clinical studies to find their place in transfusion algorithms.

Introduction: Blood and blood products are still essential for the treatment of several medical conditions for which they have no substitutes. Blood for transfusion is obtained from volunteers who go through several steps during the process of donation Association between tattoos and seropositivity to transfusion-transmissible diseases (TTDs); and it has been proposed that in certain settings having a tattoo can be an exclusion criterion for blood donation. By analogy it could be though that seropositivity to TTDs was also associated with the use of earring and body piercing. Objective: To assess whether the use of earring and/or body piercing can be indicators of seropositivity to the following TTDs: hepatitis B, hepatitis C, human immunodeficiency virus (HIV) infection, Chagas disease, and syphilis. Material and methods: Secondary analysis of a data set from a cross-sectional study conducted at the Universidade Federal de Uberlândia, and that resulted in a doctoral thesis (Nishioka,S.A.-Tattoos as indicators of transfusion-transmitted disease in Brazil: a matched hospital-based cross-sectional study.Montreal:McGill University,2000.166p). The exposure of main interest were having earring or body piercing, whereas the outcomes of interest were presence of any serologic marker of infections by hepatitis B(HBV), hepatitis C(HCV) HIV, Treponema pallidum or Trypanosoma cruzi, determined by the following tests: HBsAG, anti-HBc, anti- HCV,anti-HIV, VDRL and anti- Trypanosoma cruzi Results: No association between earring and TTDs was observed when the odds ratios were adjusted by confounders, even when the analyses were restricted to males. Body piercing was observed in only two women in the study population, and therefore could not be analyzed.Conclusion: Earring is not associated with seropositivity to TTDs, and should not be used as an exclusion criterion for blood donation. / Introdução: Sangue e derivados são ainda essenciais para tratamento de diversas condições médicas, para os quais ainda não têm substitutos. Sangue para transfusão se obtém de voluntários que passam por diversas etapas durante o processo de doação. Associação entre tatuagens e soropositividade para doenças transmissíveis por transfusão (DTT) já foi demonstrada, e proposta que em determinados locais ter uma tatuagem possa ser critério de exclusão de doação de sangue. Por analogia pode-se pensar que soropositividade para DTTs possa também estar associada com o uso de brincos e body piercing. Objetivo: avaliar se o de uso de brincos e/ou body piercing podem ser indicadores de soropositividade para as seguintes DTTs: hepatite B, hepatite C, infecção pelo vírus da imunodeficiência humana (HIV), sífilis e doença de Chagas. Material e método: Análise secundária de um banco de dados de um estudo transversal, conduzido na Universidade Federal de Uberlândia, e que resultou em uma tese de doutorado. (Nishioka, S.A. - Tattoos as indicators of transfusion-transmitted diseases in Brazil: a matched hospital based cross-sectional study. Montreal: McGill University, 2000,166p) As exposições de principal interesse foram usar brincos ou body piercing; enquanto que os desfechos de interesse foram: a presença de qualquer marcador sorológico de infecção pelo vírus da hepatite B (HBV) vírus da hepatite C (HCV), HIV, Trypanossoma cruzi ou Treponema pallidum determinada pelos seguintes testes HBsAG, anti-HBc; anti HCV; anti HIV; anti-Trypanosoma cruzi e VDRL. Resultados: Não foi observada associação entre brincos e DTTs quando os odds ratios foram ajustados pelas variáveis de confundimento, mesmo quando a análise foi restrita a indivíduos do sexo masculino. Body piercing só foi observado em duas mulheres na população estudada e, portanto não pode ser estudado. Conclusão: O uso de brincos não está associado com soropositividade para DTTs, e não deve ser um critério de exclusão para doadores de sangue. / Mestre em Ciências da Saúde

A transfusão de hemocomponentes, apesar de segura, expõe o paciente a riscos de reações adversas, as reações transfusionais. No Brasil a ocorrência dessas reações é de notificação obrigatória à Agência Nacional de Vigilância Sanitária (ANVISA). As reações notificadas tornam-se fontes de informação para ações de avaliação, controle, prevenção, melhoria da qualidade e segurança do processo transfusional. Objetivos: Identificar, descrever e analisar as reações transfusionais imediatas ocorridas num hospital da Rede Sentinela do interior do estado de São Paulo e propor medidas para ajustar a Hemovigilância no hospital. Casuística e Métodos: Realizado estudo prospectivo, descritivo, quantitativo e exploratório, por meio de ações de Hemovigilância: visita pós transfusional para busca ativa de reações transfusionais imediatas e investigação junto à equipe de trabalho, identificando motivos para subnotificação de reações. Resultados: Em 1230 hemocomponentes transfundidos, incluídos no estudo, de março a junho de 2016 e junho de 2017, foram encontradas 167 reações transfusionais imediatas, que deveriam ter sido notificadas. Porém, no período, foram notificadas apenas 22 com uma subnotificação de 145 reações (11,8% ou 117,9 reações por 1000 hemocomponentes transfundidos). A maioria das reações subnotificadas foram Reações Febris Não Hemolíticas (RFNH) e Reações Alérgicas (ALG), de gravidade leve, com imputabilidade possível, mas também foram subnotificadas reações de gravidade moderada e grave: Sobrecarga circulatória associada à transfusão (SC/TACO). As causas identificadas para subnotificação foram: desinformação do paciente, falha na monitorização de sinais vitais póstransfusionais, excesso de transfusão no período noturno com equipe de trabalho reduzida, dificuldade de identificar a reação transfusional pela equipe de trabalho, sinalizando a necessidade de capacitação periódica. Conclusões: Este estudo contribuiu para reflexão, identificação de necessidades de educação continuada em serviço e, principalmente, para conscientização da importância de uma equipe de trabalho destinada a realizar ações de Hemovigilância por meio da busca ativa de reações transfusionais. / Although the transfusion of blood components is safe, it exposes the patient to risks of adverse transfusion reactions. In Brazil, the occurrence of these reactions has to be mandatorily notified to the Brazilian Health Regulatory Agency (ANVISA). The reactions notified become a source of information for actions of assessment, control, prevention, quality improvement and safety of the transfusion process. Objectives: To identify, describe, and analyze the immediate transfusion reactions at a hospital of the Sentinela Network in the countryside of the state of São Paulo and then to propose measures to adjust hemovigilance at the hospital. Casuistic and Methods: We carried out a prospective descriptive quantitative exploratory study by the hemovigilance actions: visit after transfusion for the active search of immediate transfusion reactions and investigation with the work team, identifying the reasons for the subnotification of reactions. Results: In 1230 blood components transfused included in this study, from March 2016 to June 2017, we found 167 immediate transfusion reactions which should have been notified; however, in this period, only 22 were notified with a subnotification of 145 reactions (11.8% or 117.9 reactions per 1000 blood components transfused). Most reactions subnotified were Febrile Non-Hemolytic Reactions (FNHTR) and Alergic Reactions (ALG), with mild severity and possible imputability, but moderate and severe reactions were also subnotified; such as Transfusion-associated circulatory overload (TACO). The causes identified for subnotification were: patient misinformation, fail in monitoring vital signs after transfusion, excess of transfusions in the night shift with a reduce work team, and difficulty of the team in identifying the transfusion reaction, highlighting the need for continuous training in Hemovigilance. Conclusions: This study contributed to reflect on and identify the needs for continuing education in the service mainly to make the health team aware of the importance to take hemovigilance actions by the active search of transfusion reactions.

IntroductionLa drépanocytose est l’affection génétique la plus répandue dans le monde plus particulièrement en Afrique subsaharienne, considérée à juste titre comme l’une des régions originaires de la mutation drépanocytaire avec de fortes prévalences. Elle est reconnue comme un problème de santé majeur par la communauté internationale en raison de sa morbidité et de sa mortalité élevées. Au Mali, environ 5 à 6 milles naissances de drépanocytaires sont enregistrées par an [Diallo, 2008] et ils auront besoin d’une prise en charge médicale spécifique. Le Centre de Recherche et de Lutte contre la Drépanocytose (CRLD) situé à Bamako est le seul centre de traitement spécifique dédié à la lutte contre la drépanocytose au Mali. Il reçoit des patients drépanocytaires du Mali et de la sous région. Ces patients sont pour la plupart vus au stade de complications puisqu’il n’existe pas de programme de dépistage systématique dès la naissance et à fortiori de suivi.La transfusion sanguine intervient dans une large mesure pour la prise en charge thérapeutique de ces patients. Acte thérapeutique essentiel sur le continent Africain en raison de la fréquence d’anémies de diverses origines (certaines nécessiteront un traitement de la cause).Cette transfusion sanguine comporte des risques non négligeables en Afrique, notamment dans le domaine des agents transmissibles par le sang. Un dépistage systématique des infections par le virus de l’immunodéficience humaine (VIH), le virus de l’hépatite C (VHC), le virus de l’hépatite B (VHB) et le tréponème, agent de la syphilis, est en vigueur sur tous les dons de sang à Bamako, mais les prévalences élevées de ces agents infectieux dans la population générale dont sont issus les donneurs de sang incitent à penser que le risque transfusionnel résiduel doit être important. Dans le but de renforcer la sécurité transfusionnelle au Mali, nous avons entrepris des études prospectives et rétrospectives chez les donneurs de sang et chez les drépanocytaires transfusés, ceci afin d’identifier les problèmes spécifiques liés à la thérapeutique transfusionnelle chez les drépanocytaires et de proposer une meilleure stratégie pour leur prise en charge.Méthodologie :Nous avons conduit une série d’études, visant à déterminer :- les caractéristiques des donneurs, des dons de sang et de l’organisation des centres de transfusion en Afrique subsaharienne francophone ;- la séroprévalence des agents infectieux transfusionnels majeurs (VIH, VHB, VHC) pour les dons de sang effectués au CNTS du Mali et chez les patients drépanocytaires recrutés au CRLD. - la fréquence de l’allo-immunisation anti-érythrocytaire avant et après la transfusion sanguine chez les drépanocytaires.- identifier les problèmes liés au dépistage néonatal et au suivi des drépanocytaires dépistés au Mali.Les donneurs de sang (volontaires et familiaux) ont été inclus selon les critères du don en vigueur au Mali. Le diagnostic de la drépanocytose a été réalisé par une technique de chromatographie liquide à haute performance (CLHP) avant inclusion des patients.Le dépistage des infections virales a été effectué par une méthode immunoenzymatique (ELISA) et la recherche des anticorps anti-érythrocytaire par un test de Coombs indirect.Résultats :Dans les sept pays, les donneurs de la tranche d’âge 18 à 30 ans étaient les plus nombreux, représentant plus de 45 % dans tous les centres, et plus de 70%dans quatre centres sur sept. Les donneurs masculins étaient les plus nombreux (plus de 70% de l’ensemble). Les donneurs étaient majoritairement volontaires (plus de 70 %), sauf au Cameroun et au Mali où ils représentaient respectivement 25,5 et 30 %. Quatre pays, dont ces deux derniers, avaient moins de 50 % de donneurs réguliers.Sur un total de 25 543 dons de sang recueillis au CNTS de Bamako en 2007, les séroprévalences des agents infectieux dépistés étaient de :2,6 % pour le VIH; 3,3 % pour le VHC et 13,9 % pour le VHB. En fonction du type de don, il y’avait une différence statistiquement significative (p <0,05) entre ces séroprévalences et plus élevées chez les donneurs familiaux que chez les donneurs volontaires bénévoles.Chez les 133 drépanocytaires transfusés au moment de leur inclusion dans l’étude, les séroprévalences des infections virales observées étaient de :1%, 3% et 1% respectivement pour les VIH, VHB et VHC. Trois cas de séroconversion post-transfusionnelle ont été observés. Tous avaient reçu du sang de donneurs familiaux. L’allo-immunisation anti-érythrocytaire était observée chez 4,4% (4/90) des drépanocytaires avec antécédents transfusionnels au moment de leur inclusion; les anticorps observés étaient de type anti D (un cas), anti C (deux cas) et un anti c (un cas). Elle n’a été observée chez aucun patient drépanocytaire ayant reçu leur 1ère transfusion au CRLD, avec exclusivement des concentrés de globules rouges phénotypés.Concernant le dépistage néo-natal de la drépanocytose, sur un total de 2480 nouveau-nés dépistés, 16 étaient atteints de l’affection. Aucun suivi médical programmé n’a pu être réalisé.Conclusion :Les prévalences relativement élevées des agents infectieux dans les dons de sang effectués par des donneurs familiaux majoritaires et les séroconversions observées après transfusion sanguine, justifient une politique de sécurisation des procédures de transfusions chez les drépanocytaires basée notamment sur le recrutement de donneurs volontaires.L’amélioration de la survie des patients drépanocytaires passe par la mise en place de programmes de dépistage précoce et de suivi régulier, mais si cette stratégie est réalisable du point de vue du diagnostic, il n’en demeure pas moins qu’elle soulève des problèmes de financement de cette activité et de sa pérennisation ;ces aspects doivent faire l’objet de réflexions pour une solution à long terme. / Introduction Sickle cell disease is the most common genetic disorder in the world, especially in sub-Saharan Africa where sickle cell mutation with high prevalence’s is originated high. It is recognized as a major health problem by the international community due to its morbidity and mortality. In Mali, around 5-6000 newborns annually affected by sickle cell disease [Diallo, 2008] and they will require specific medical that is by the “Centre de Recherche et de Lutte contre la Drépanocytose » (CRLD) in Bamako. This is the unique Malian center where sickle cell patients from Mali and the sub-region are treated. Because of the lack of systematic screening program at birth, most of the patients are seen at the stage of complications. Blood transfusion is largely used for therapeutic management of these patients. It constitutes an essential therapeutic approach against anemia of highly prevalent in Africa various origins (some requiring also treatment of the cause). However, blood transfusion means significant risks, particularly in area of high prevalence of transfusion transmissible infectious agents. A systematic screening for viral infections like human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus(HBV) and Treponema agent of syphilis is required for all blood donations in Bamako, but the high prevalence of these infectious agents in the general population, i.e. blood donors, suggest that the residual risk of transfusion must be important.In order to enhance blood transfusion safety in Mali, we undertook prospective and retrospective studies in the population of blood donor and sickle cell patient transfused to identify transfusion related adverse events and especially for SCD’ patients, suggest a better strategy for their follow-up. Methodology:We conducted a sery of studies which aims to determine:- The characteristics of donors, blood donation and the organization of blood transfusion centers in sub-Saharan French speaking Africa;- The seroprevalence of major infectious agents (HIV, HBV, and HCV) in blood donations at the CNTS in Mali and in sickle cell patients at CRLD. The frequency of anti-erythrocyte allo immunization before and after blood transfusion in sickle cell disease patients;- Identification of difficulties related to newborn screening and monitoring of sickle cell patients in Mali.Blood donors (volunteers and family) were included according to the criteria of blood donation in Mali.Hemoglobin type in sickle cell was determined by the technique of high performance liquid chromatography (HPLC) before patients’ inclusionScreening for viral infections was performed by enzyme immunoassay (ELISA) and the search for anti-erythrocyte antibodies by indirect Coombs test. ResultsIn the seven countries, donors aged from 18 to 30 years old were more represented i.e. 45% in all centers and more than 70%in four of the seven centers. More than 70% of blood donors were males. Donors were mostly volunteers (over 70%), except in Cameroon and Mali accounting for25.5% and30%, respectively four countries, including Cameroon and Mali had less than,50% of regulars donors.Of the 25 543 blood donations collected at the CNTS in Bamako in 2007, seroprevalence of infectious agents detected represented: 2.6%, 3.3%, and 13.9% for HIV, HCV, and HBV respectively. A statistical significative difference (p<0.05) was observed between family and volunteer donors in term of seroprevalence.the 133 sickle cell patients who received blood transfusion at inclusion, the seroprevalence of viral infections was1%, 3%, and 1%,for HIV, HBV, and HCV, respectively. Three cases of post-transfusion seroconversion were observed but only in sickle cell patients who received blood from family donors.Anti-erythrocyte alloimmunization was observed in 4.4% (4/90) among sickle cell patients with blood transfusion history at the time of inclusion; observed antibodies were anti type D (one case), anti C (two cases) and anti c (one case). However, no case was observed in any sickle cell patients, who received phenotyped RBC at CRLD,For neonatal screening, among the 2480 newborns, 16 were affected. However no scheduled medical follow-up was realized. Conclusion The relatively high prevalence’s of infectious agents in family donors, who represented the majority of blood donors, and of seroconversion observed after blood transfusion in sickle cell patients justify a security policy of blood transfusion procedures based, particulary for SCD patients, blood donations by volunteers. Improved survival of patients with sickle cell disease should be based on the development of early detection programs and regular monitoring. However if this strategy is feasible in terms of diagnosis ,it raises problems at funding for this activity and also of; those should be the subject of discussion for a long term solution / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished

Le paludisme ou malaria est une maladie parasitaire due à un protozoaire. Il est transmis principalement à l'homme par la piqûre de la femelle d'un moustique du groupe des anophèles. La transfusion sanguine représente la 3e voie potentielle de transmission de Plasmodium. L'incidence du paludisme a entraîné une augmentation de la proportion des donneurs de sang ayant été en contact avec le parasite. Le premier objectif de ce travail de thèse est d'analyser l'immune-réactivité de marqueurs biologiques de dépistage de Plasmodium dans les poches de sang pour prévenir le paludisme transfusionnel et plus spécifiquement, il s'agit de déterminer par goutte épaisse (GE) et Enzyme Linked lmmunosorbent Assay {ELISA), la prévalence du paludisme asymptomatique chez les donneurs de sang au Sud du Bénin. Le second objectif est de répertorier les marqueurs moléculaires les plus adéquats pour la recherche d'antigène et d'anticorps de Plasmodium, utilisables en dépistage de masse dans les centres de transfusion sanguine. / Malaria is a disease due a protozoan. lt is transmitted to humans by the bite of a mosquito form Anopheles group. Blood transfusion is the third potential way of malaria transmission. Incidence of Malaria has increased the proportion of blood donors suspected to be contaminated by Plasmodium sp. The goal of that study is to determine the immunoreactivity of some biomarkers that could be used for the prevention of the blood transfusion transmitted malaria. For that purpose we used thick and thin blood film microscopical determination and an Enzyme Linked lmmunoSorbent Assay technology detecting malaria antigen (pan-pLDH) and malaria antibodies. These methods were used for the screening of 2515 blood donors during ten following months insouthern-Benin, sample were separated in the 4 following seasons observed in Western Africa.

Les Encéphalopathies Spongiformes transmissibles (EST) sont des maladies neurodégénératives fatales caractérisées par l’accumulation d’un conformère anormal (PrPSc) d’une protéine de l’hôte (PrP). Chez l’homme, plusieurs centaines de cas de transmissions iatrogènes de la maladie de Creutzfeldt Jakob (MCJ) ont été identifiées, notamment chez des patients ayant fait l’objetd’ une greffe de dure-mère, de cornée ou des injections d’hormones de croissance extractives. Plus récemment, plusieurs cas du variant de la maladie de Creutzfeldt Jakob (vMCJ) ont été observés chez des patients transfusés avec des produits sanguins issus de donneurs en incubation de la maladie. D’un point de vue sanitaire, l’évaluation du risque de contamination interindividuelle par des tissus ou des fluides biologiques issus de patients atteints représente un enjeu important en matière de santé publique. La première partie de notre travail a consisté à comparer la sensibilité relative de modèles de souris transgéniques sur-exprimant la PrP à celle de l’hôte conventionnel exprimant la même séquence. Les résultats obtenus ont validé le concept d’une absence d’impact du niveau d’expression de la PrP ou du fond génétique de l’hôte sur la sensibilité finale du modèle à l’infection. A l’aide de ces modèles de souris transgéniques, nous avons alors mesuré les niveaux d’infectiosité dans le sang de patients atteints de différentes formes d’’EST. Chez un patient atteint de vMCJ, nous avons mis en évidence de faibles niveaux d’infectiosité dans les concentrés de globules rouges, les leucocytes et le plasma. Nous avons également pu détecter de l’infectiosité dans le plasma issu de 2 patients atteints de sMCJ sur 4 testés. Parallèlement à ces expériences, nous avons démontré dans un modèle expérimental d’infection chez le mouton, que l’administration de 104 à 105 leucocytes suffisent à transmettre par voire transfusionnelle la maladie. Ces résultats soulignent l’intérêt et les limites de la leuco-déplétion appliquée de manière standard en médicine transfusionnelle, pour limiter les risques de transmission du vMCJ. Enfin, nous avons testé la capacité de différents outils in vitro à détecter la présence des Prions dans le sang. / Transmissible spongiform encephalopathies (TSE) are fatal neurodegenerative disorders occurring in a wide spectrum of animals. They are characterized by accumulation of abnormally folded conformers (PrPSc) derived from normal cellular PrP protein (PrP) of the host. In human, many iatrogenic transmissions of Creutzfeldt Jakob disease (CJD) have been reported after dura mater graft, corneal graft or extractive growth hormone injections, prepared from affected donors. More recently, several cases of vCJD transmissions were reported in individuals that were transfused with blood from asymptomatic donors that subsequently developed vCJD. Risk assessment of interindividual transmission with contaminated tissues or body fluids remains a major public health issue. In a first part, we validated the final pertinence of infectious titers as measured in mice overexpressing PrP to the risk of transmitting the disease in the natural host species. In a second time, we used this model to evaluate the presence of infectivity in blood from TSE affected patients. We were able to detect the presence of infectivity in erythrocytes, leukocytes, and plasma of 1 person with vCJD and in the plasma of 2 out of 4 persons whose tests were positive for sporadic CJD. We then demonstrated in a sheep TSE model, that intravenous administration of 104 to 105 leucocytes was sufficient to cause disease in recipient sheep, underlying the efficacy and potential limits of leuko-reduction processes that are currently applied in transfusion medicine to mitigate the TSE transmission risk. Finally, using the same model, we tested different in vitro methods to detect prions in blood.