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.

Samfundet Jehovas vittnen avsäger sig blodtransfusion på grund av sin religiösa tro. Sjukvården ställs inför etiska problem när det uppstår en situation då patienten behöver blodprodukter. För vårdaren uppstår etiska konflikter mellan viljan att rädda liv, medicinska och juridiska aspekter samt patientens autonomi. Syftet med vår uppsats är att belysa de etiska problem som vårdaren kan möta i sjukvårdspraxis. Metoden som använts är en kvalitativ litteraturstudie och bygger på fyra vetenskapliga artiklar och en avhandling. I resultatet framgick det att det är en konfliktfylld situation då patienten nekar blodtransfusion och vårdaren har en roll att rädda liv men då går emot patientens självbestämmanderätt. De olika företrädarna för professionerna har olika syn på hälsa. Sjuksköterskan försätts i en konflikt mellan att respektera patientens autonomi eller att utföra läkarordinationen. För vårdpersonalen uppstår ytterligare ett problem när patienten är medvetslös och inte kan ge sin aktuella ståndpunkt gällande behandling. I resultatdiskussionen belyser vi att det inte finns några konkreta lösningar på de etiska problemen och att sjukvårdarna är dåligt förberedda på att hantera situationer som dessa. Vårdpersonal bör vara medveten om vilken inverkan kultur och religion har på människors liv och hur man ser på hälsa och sjukdom. Utbildning inom etik menar vi är en förutsättning för att kunna hantera de etiska problem som uppstår när patienten tillhörande Jehovas vittne avsäger sig blodtransfusion. Bristande kunskap i sjukvårdspraxis finns och därför behövs det vidare forskning och utbildning inom området för att kunna hantera dessa etiska problem. / Program: Sjuksköterskeutbildning

Trata-se de uma revisão integrativa da literatura com objetivo de identificar e analisar as evidências oriundas de estudos primários que abordaram a relação entre a transfusão sanguínea e a ocorrência da infecção de sítio cirúrgico, em pacientes adultos submetidos à cirurgia eletiva. A busca foi realizada em abril de 2012 nas bases de dados PUBMED/ MEDLINE, CINAHL, LILACS e Biblioteca Cochrane e utilizou-se o limite dos estudos indexados nos últimos 10 anos. Para a busca nas bases de dados eletrônicas foram utilizadas combinações entre os descritores controlados transfusão sanguínea, transfusão de componentes sanguíneos, cirurgia eletiva e infecção de ferida cirúrgica e os não-controlados infusão sanguínea, procedimento cirúrgico eletivo, cirurgia de não urgência e infecção de sítio cirúrgico, as quais resultaram na identificação de 2195 referências, dentre essas, 2112 foram excluídas devido a ausência em relação ao tema a partir da leitura de título e resumo. Assim, 73 estudos mostraram-se elegíveis e foram lidos na íntegra, dentre os quais, 50 estudos não foram selecionados e cita-se como motivo de exclusão para cinco estudos, que não analisavam a relação da infecção de sítio cirúrgico e a transfusão sanguínea, dois estudos incluíam indivíduos com idade inferior a 18 anos, 33 estudos consideravam cirurgias de urgência e emergência, quatro estudos transfundiam plasma e plaquetas e seis estudos não referenciavam infecção de sítio cirúrgico. Dentre os 33 estudos selecionados, 16 constavam de estudos repetidos e 17 estudos primários foram selecionados e incluídos na amostra, pois atenderam aos critérios de seleção da revisão. Para extração dos dados foi utilizado um instrumento validado. A análise dos dados foi descritiva e apresentada em duas categorias temáticas: pacientes que recebiam transfusão sanguínea e apresentavam a infecção de sítio cirúrgico como desfecho infeccioso; e pacientes com infecção de sítio cirúrgico, para os quais a transfusão sanguínea foi verificada como um fator de risco independente. As variáveis clínicas e cirúrgicas relacionadas com maior frequência e significância nos estudos foram: níveis de hemoglobina, perda sanguínea intra-operatória, quantidade de sangue transfundido, tempo de operação, escore do ASA, classificação da cirurgia e uso de antibiótico profilático. E a maior ocorrência de infecção de sítio cirúrgico foi verificada em mulheres, de maior idade e índice de massa corporal para obesidade. Um aspecto positivo a ser ressaltado é que a definição da infecção de sítio cirúrgico utilizada nos estudos primários incluído foi a mesma. No entanto, há necessidade de consenso para os níveis de hemoglobina indicativos de transfusão sanguínea e a implementação de assistência de enfermagem direcionada ao atendimento das reais necessidades deste paciente, minimizando os riscos e complicações inerentes ao procedimento anestésico-cirúrgico, educação para e vigilância pós-alta hospitalar para identificação precoce de infecção de sítio cirúrgico em pacientes submetidos à Obrigada pela força, cumplicidade e convivência. transfusão sanguínea. / The aim of this integrative literature review was to identify and analyze evidence from primary studies on the relation between blood transfusion and the occurrence of surgical site infection in adult patients submitted to elective surgery. The search was accomplished in April 2012 in the databases PUBMED/ MEDLINE, CINAHL, LILACS and the Cochrane Library and was limited to studies indexed in the last 10 years. For the electronic database search, combinations were used among the controlled descriptors blood transfusion, blood component transfusion, elective surgery and surgical site infection and the non-controlled descriptors blood infusion, elective surgical procedure, non-urgent surgery and surgical site infection, which resulted in the identification of 2195 references. Of these, 2112 were excluded due to the lack of relation with the theme, based on the reading of the title and abstract. Thus, 73 studies were eligible and were fully read, 50 of which were not selected. For five studies, the reason for exclusion was that they did not analyze the relation between the surgical site infection and the blood transfusion, two studies included individuals younger than 18 years of age, 33 studies considered urgency and emergency surgeries, four studies transfused plasma and platelets and six studies did not refer to surgical site infection. Among the 33 selected studies, 16 were repeated, so that 17 primary studies were selected and included in the sample, as they complied with the selection criteria for the review. To extract the data, a validated instrument was used. Data analysis was descriptive and presented in two thematic categories: patients who received a blood transfusion and presented surgical site infection as an infectious outcome; and patients with surgical site infection, for whom the blood transfusion was verified as an independent risk factor. The most frequently and significantly related clinical and surgical variables in the studies were: hemoglobin levels, intraoperative blood loss, amount of blood transfused, duration of surgery, ASA score, surgery classification and use of prophylactic antibiotics. And the highest incidence levels of surgical site infection were found in older women whose body mass index indicated obesity. One positive aspect to be highlighted is that the definition of surgical site infection used in the included primary studies was the same. A consensus is needed on what hemoglobin levels indicate blood transfusion and the implementation of nursing care in response to these patients\' actual needs, minimizing the risks and complications inherent in the anesthetic- surgical procedure, education for and surveillance after hospital discharge with a view to the early identification of surgical site infection in patients submitted to blood transfusion.

A malária transmitida por transfusão (MTT), embora seja um evento raramente relatado em áreas não endêmicas ou de baixa endemicidade, representa um desafio devido à ocorrência de infecções assintomáticas e à possibilidade de sobrevivência de Plasmodium em hemácias estocadas por até três semanas a temperaturas entre 2 e 6ºC. No Estado de São Paulo, quatro casos de MTT foram relatados, incluindo uma morte. Os doadores infectados foram identificados como portadores assintomáticos que viviam ou haviam se deslocado para o bioma Mata Atlântica do estado. Nesses doadores, geralmente as densidades parasitárias são baixas e indetectáveis pela gota espessa ou testes rápidos. O uso de plataformas incluindo testes sorológicos poderia detectar doadores suspeitos de infecção por Plasmodium, minimizando a possibilidade de MTT. Nesse sentido, o objetivo deste estudo foi padronizar a produção de antígeno recombinante MSP119 de P. vivax, que é a espécie mais prevalente no Brasil, e validar o teste ELISA-PvMSP119, visando à aplicação em serviços hemoterápicos brasileiros de áreas não endêmicas para malária. O antígeno recombinante produzido em condições desnaturantes mostrou-se adequado para a produção em larga escala, pela facilidade de obtenção e purificação. Os resultados de estabilidade obtidos em três lotes-piloto indicaram validade de pelo menos 27 meses sem perda de reatividade. Além disso, o teste apresentou 96,95% de sensibilidade em 197 soros de pacientes com gota espessa positiva para P. vivax e especificidade de 100,00% utilizando soros de 101 indivíduos controles sadios e 99,26% quando considerados também 168 amostras de soro de pacientes com outras doenças. O coeficiente de variação das amostras positivas foi <= 3,8% para a repetitividade e <= 10,6% para a reprodutibilidade. Quanto à reatividade cruzada, obtiveram-se falsos resultados positivos com amostras de doença de Chagas (5,88%) e fator reumatoide (6,67%). Após a validação, avaliou-se a prevalência de anticorpos IgG anti-MSP119 de P. vivax entre doadores de sangue do Sudeste do Brasil, considerados aptos à doação, ensaiando 1.974 amostras de plasma de bancos de sangue, sendo 1.309 do Estado São Paulo (SP) e 665 do Estado do Rio de Janeiro (RJ). A positividade entre as amostras de SP foi 1,15% (N = 15) e entre as do RJ foi 1,65% (N = 11). O índice de reatividade (IR) das amostras positivas variou entre 8,98-1,16 (SP) e 13,03-1,08 (RJ). Em SP e RJ, maior positividade foi encontrada nos municípios que têm contato com o bioma Mata Atlântica e no RJ, também no bairro da Tijuca, onde se encontra a Floresta da Tijuca. A presença de anticorpos IgG anti-P. vivax não é necessariamente um marcador de parasitemia ou doença, porém aponta para o risco de MTT, mesmo em áreas de baixa endemicidade, pois doadores assintomáticos podem ser aceitos com base em triagem clínica. Estes achados constituem-se em alerta que nos impele a rever os critérios adotados para a seleção dos doadores, com o objetivo de reduzir o risco de MTT nessas áreas sem perder doações. / In non-endemic and low endemic areas, transfusion-transmitted malaria (TTM) is a rarely reported event, representing a major challenge, essentially due to the occurrence of asymptomatic infections and to the possibility of Plasmodium survival up to three weeks in stored red blood cells at temperatures between 2 and 6ºC. In São Paulo State, four TTM were detected, including one death. Infected donors were identified as asymptomatic carriers that lived or that had displacements to the Atlantic forest biome in the state. In these donors generally the parasite densities are low and undetectable in the thick blood smear or rapid diagnostic tests. The use of platforms including serological tests might point out donors suspected of harboring Plasmodium, minimizing the possibility of TTM. Accordingly, the aim of this study was to standardize the production of P. vivax MSP119 recombinant antigen, which is the most prevalent species in Brazil, and validate ELISA-PvMSP119, aiming at the application in Brazilian haemotherapic services in malaria non-endemic areas. The recombinant antigen produced under denaturing conditions was suitable for large-scale production, due to the ease of obtaining and purification. The results of stability obtained in three pilot batches indicated that it was valid for at least 27 months without loss of reactivity. Furthermore, the test showed 96.95% sensitivity in sera from 197 patients with positive thick-blood smear for P. vivax and 100.00% specificity in sera from 101 healthy controls, and 99.26% when considered also 168 samples from patients with other diseases. The variation coefficient of positive samples was <= 3.8% for repeatability and <=10.6% for reproducibility. For cross-reactivity, false positive results were obtained with Chagas\' disease (5.88%) and rheumatoid factor (6.67%) samples. After validation, we evaluated the prevalence of IgG anti-MSP119 antibodies to P. vivax among blood donors in Southeastern Brazil, considered suitable for donation, rehearsing 1,974 plasma samples from blood banks, being 1,309 from the State of São Paulo (SP) and 665 from the State of Rio de Janeiro (RJ). The positivity among samples from SP was 1.15% (N = 15) and in RJ was 1.65% (N = 11). The reactivity index (RI) of the positive samples ranged from 8.98 to 1.16 (SP) and from 13.03 to 1.08 (RJ). In SP and RJ, highest positivity was seen in Municipalities in contact to the Atlantic Forest biome, and in RJ, also in the Tijuca neighborhood, where there is the Tijuca Forest. The detection of IgG antibodies is not necessarily a marker of parasitemia or disease, however, points out to the risk of TTM, even in areas of low endemicity, since asymptomatic donors could be accepted based on clinical screening. These findings constitute an alert that impel us to review the adopted criteria for screening of the donors aiming to reduce the risk of TTM in these areas without losing donations.

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No. of bitstreams: 1 neto_t_me_bot.pdf: 2190291 bytes, checksum: 9e23877fdf7cbe05ad85fc4d79544592 (MD5) Previous issue date: 2016-12-09 / A Coordenação Geral de Sangue e Hemoderivados CGSH, do Ministério da Saúde, comprometida com a missão de elaborar políticas que promovam o acesso da população à atenção hematológica e hemoterápica de forma segura e com qualidade, desenvolve suas ações em consonância com os princípios e as diretrizes do Sistema Único de Saúde – SUS e através da ANVISA implantou em 2001 a Avaliação Externa da Qualidade em Imuno-hematologia (AEQIH) contando com 8 unidades produtoras (UP). Em 2005 o Hemocentro de Botucatu passou a integrar as UP. Este trabalho tem como objetivo avaliar o desempenho dos serviços de hemoterapia (SH) da área de abrangência da Grande São Paulo, sob responsabilidade da UP de Botucatu no período de 2005-2015 levando em consideração diferentes indicadores: número de serviços atendidos/índice de adesão; erros e acertos nas técnicas de tipagem ABO e RhD, pesquisa de anticorpos irregulares (PAI), identificação de anticorpos irregulares (IAI), teste da antiglobulina direta (TAD), prova cruzada (PC) e fenotipagem eritrocitária (FE). A análise estatística realizada foi a de regressão linear, teste de correlação de Spearman e Curva ROC. Durante os 10 anos foram enviados 29 painéis práticos contendo 4 tipagens ABO e RhD (n=10.382), 2 amostras para PAI, IAI e TAD (n=5.191 respectivamente), PC (n=1.611) e FE (n=1.074) e 21 avaliações teóricas (18.975 questões). A média de SH participantes durante o período determinado foi de 89,5. O índice de crescimento, levando em consideração o número de serviços avaliados em 2005 e aqueles em 2015, indica um crescimento de 26,6%. Quanto à avaliação dos painéis práticos, o desempenho dos indicadores avaliados foi: ABO> RhD> PC>TAD>PAI>IAI>FE. Na avaliação individual o desempenho dos indicadores avaliados foi: IAI>PAI>FE>PC>ABO>TAD>RhD. Foram identificados 28 SH com o pior desempenho em mais de um parâmetro avaliado (24,13% do total): dos sete parâmetros avaliados, erraram dois deles (71%), três (11%), quatro (14%) e cinco (4%). O teste de correlação de Spearman identificou que o pior desempenho prático tem relação com o perfil dos serviços que não executam determinadas técnicas, bem como aqueles que têm dificuldade de responder a questionários. O percentual geral de acertos da avaliação teórica não apresenta tendência de resultados estáveis. O percentual individual de acertos da avaliação teórica varia de 80% a 99,9%. / The General Coordination of Blood and Hemoderivatives, of the Ministry of Health, committed to the mission of developing policies that promote the population's access to hematological and hemotherapeutic care in a safe and quality way, develops its actions in accordance with the principles and guidelines Of the Unified Health System and through ANVISA implemented in 2001 the External Evaluation of Quality in Immunohematology with 8 production units (PU). In 2005 the Botucatu Blood Transfusion Center became part of the UP. This study aims to evaluate the performance of hemotherapy services (HS) in the Greater São Paulo area, under the responsibility of the PU of Botucatu in the period 2005-2015, taking into account different indicators: number of services attended / rate of adherence; Errors in ABO and RhD typing techniques, irregular antibody test (IAT), identification of irregular antibodies (IAI), direct antiglobulin test (DAT), cross-test (CT) and erythrocyte phenotyping (EP). Statistical analysis was performed using linear regression, Spearman correlation test and ROC curve. During the 10 years, 29 practical panels containing 4 ABO and RhD typing (n = 10,382), 2 samples for IAT, IAI and DAT (n = 5,191 respectively), CT (n = 1,611) and EP (n = 1,074) were sent and 21 theoretical evaluations (18,975 questions). The mean number of participants during the study period was 89.5. The growth rate, taking into account the number of services evaluated in 2005 and those in 2015, indicates a growth of 26.6%. Regarding the evaluation of the practical panels, the performance of the indicators evaluated was: ABO>RhD>CT>DAT>IAT>IAI>EP. In the individual evaluation, the performance of the indicators evaluated was: IAI>IAT>EP>CT>ABO>DAT>RhD. RESULTS: Twenty-eight HS patients (71%), three (11%), four (14%) and five (11%) were found to be the worst performers in more than one parameter evaluated (24.13% of the total). The Spearman correlation test identified that the worst practical performance is related to the profile of services that do not perform certain techniques, as well as those that have difficulty answering questionnaires. The general percentage of correctness of the theoretical evaluation does not present a trend of stable results. The individual percentage of correctness of the theoretical evaluation varies from 80% to 99.9%.

The purpose of this dissertation was to evaluate outcomes associated with blood component (BC) transfusion in adult trauma patients. Specific aims were to: 1) explore the relationship between traumatic injury, hemorrhage, and BC transfusion, focusing on consequences of the component storage lesion through presentation of a conceptual model; 2) systematically review research literature comparing outcomes of massively transfused major trauma patients based on ratios of BCs received; 3) evaluating the relationship between type of blood transfusion trauma patients received (whole blood versus BCs) and mortality likelihood after controlling for demographic and clinical variables; 4) evaluating the relationship between volume and ratio of BCs transfused to trauma patients and development of inflammatory complications (ICs) after controlling for demographic and clinical variables. Specific aim one was addressed through the development of a conceptual model, depicting the current state of knowledge regarding the storage lesion, and short-/long-term outcomes of traumatic injury, hemorrhage, and blood transfusion. The second specific aim was addressed through a systematic review of studies that grouped critically injured, massively transfused patients based on ratios of BCs they received, and compared clinical outcomes among groups. Findings from this analysis revealed increased survival likelihood with massive transfusion of BCs in a 1:1:1 (packed red blood cells [PRBCs], fresh frozen plasma [FFP], platelets [PLTs]) fashion. The third specific aim involved a secondary analysis of the National Trauma Data Bank to evaluate the relationship between type of transfusion trauma patients received (whole blood versus BCs) and mortality. Patients who received BCs experienced a higher mortality likelihood compared with those who received whole blood. The fourth specific aim was addressed through a secondary analysis of the Inflammation and Host Response to Injury Trauma-Related Data Base, to evaluate the relationship between volume and ratio of BCs transfused and development of ICs in patients with major trauma. Findings revealed that total transfused volume of PRBCs, injury severity, and comorbidities were associated with development of ICs. There were no differences in time to complication between PRBCs:FFP or PRBCs:PLTs ratio groups.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 5 uppsatser.

Από την δεκαετία του '70 είναι γνωστό ότι οι αλλογενείς μεταγγίσεις αίματος (ABT) προκαλούν ανοσοκαταστολή, ωστόσο, μετά το 1990 έγινε γνωστό ότι για το φαινόμενο αυτό ευθύνεται ο Τ λεμφοκυτταρικός πληθυσμός των ρυθμιστικών κυττάρων (Tregs). Στην παρούσα εργασία, μελετήθηκε η επίδραση της μετάγγισης σε ασθενείς που είχαν υποβληθεί σε ολική ή μερική αρθροπλαστική γόνατος ή ισχίου, στον πληθυσμό των φυσικών (nTreg) και επαγώγιμων (iTreg) Τ ρυθμιστικών κυττάρων. Στους ίδιους ασθενείς μελετήθηκε και η αλλαγή προτύπου στην έκκριση των κυτταροκινών. Συλλέχθηκαν δείγματα ολικού αίματος από 46 ασθενείς, 7 άντρες και 39 γυναίκες. Από αυτούς, οι 36 ασθενείς έλαβαν μετάγγιση (Group1) ενώ οι 10, δεν έλαβαν. Η συλλογή των δειγμάτων έγινε πριν την εγχείρηση (BS), αμέσως μετά το χειρουργείο (Day0), μια εβδομάδα μετά (Day7), ένα μήνα μετά (1month) και κατά τον επανέλεγχο των ασθενών (>3months). Στα δείγματα έγινε απομόνωση των PBMC και καθορίστηκε το ποσοστό των CD4+CD25+Foxp3+ και CD4+CD25high/+CD127low/- Tregs με την μέθοδο FACS ενώ στο πλάσμα καθορίστηκαν τα επίπεδα των κυτταροκινών με τις μεθόδους Cytometric Bead Array (CBA) και ELISA. Επιπρόσθετα, μελετήθηκε η λειτουργικότητας των Treg από δείγμα αίματος ασθενών μέσα στην πρώτη εβδομάδα μετά το χειρουργείο. Καλλιεργήθηκαν διάφοροι λόγοι Tregs: Teff για 72 ώρες, παρουσία PHA και CFSE. Με την μέθοδο Cytometric Bead Array (CBA) καθορίστηκαν τα επίπεδα των κυτταροκινών IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ ενώ με την μέθοδο της ELISA καθορίστηκαν τα επίπεδα των TNF-α και των υποδοχέων TNF-RI(p55/p60) και TNF-RII(p75/p80) καθώς επίσης και οι TGF-β1 και TGF-β2. Από τα πειράματα προέκυψε ότι οι πληθυσμοί τόσο των φυσικών CD4+CD25+Foxp3+ όσο και των επαγώγιμων CD4+CD25high/+CD127low/- Tregs, αυξάνονται μετά το χειρουργείο (day 0), μετά την μετάγγιση, ενώ μειώνονται την πρώτη εβδομάδα μετά το χειρουργείο. Αντίθετα αποτελέσματα παρατηρήθηκαν στους ασθενείς οι οποίοι υποβλήθηκαν σε χειρουργείο αλλά δεν μεταγγίστηκαν. Με τα πειράματα λειτουργικότητας, φάνηκε ότι τα Tregs ήταν λειτουργικά και ικανά να προκαλούν αναστολή του πολλαπλασιασμού των Teff. Σχεδόν όλες οι κυτταροκίνες που αναλύθηκαν, οι IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, ο υποδοχέας TNF-RI(p55/p60) και TNF-RII(p75/p80) και TGF-β2 εμφάνισαν αύξηση μετά το χειρουργείο, μετά την μετάγγιση. Ωστόσο, μόνο η αύξηση της IL-6, και των υποδοχέων TNF-RI(p55/p60) και TNF-RII(p75/p80) ήταν στατιστικώς σημαντική μετά το χειρουργείο, μετά την μετάγγιση. Τα επίπεδα του TGF-β1 μειώθηκαν μετά το χειρουργείο, μετά την μετάγγιση (Th3 απόκριση). Συμπερασματικά, τα ποσοστά των Tregs αυξήθηκαν στους ασθενείς που υποβλήθηκαν σε αρθροπλαστική και μεταγγίστηκαν. Οι πληθυσμοί των Tregs παρέμειναν αυξημένοι μέχρι και τον πρώτο μήνα μετά το χειρουργείο. Τα Tregs είναι λειτουργικά και ικανά να καταστέλλουν τον πολλαπλασιασμό των Teff, παρουσία PHA. Μετά το χειρουργείο, ύστερα από μετάγγιση, τα επίπεδα των IL-6, TNF-RI και TNF-RII αυξάνονται ως αντίδραση κατά του μοσχεύματος. Μετά την εγχείρηση (day 0) και μετά από μετάγγιση, οι ασθενείς αναπτύσσουν Th1 απόκριση και πολλαπλασιασμό των Tregs. Σταδιακά, τα Tregs καταστέλλουν τις προφλεγμονώδης αποκρίσεις μέχρι να επανέλθει η ισορροπία των ληπτών μετά την εγχείρηση. / Clinical and experimental studies have established that allogeneic blood transfusion (ABT) can cause immunosuppression. In this work we determined whether and to which extend Tregs contribute to this effect. Material and methods: Heparinized peripheral blood samples were collected from 46 patients (7 male and 39 female, age 28-88 years) that underwent joint replacement surgery. The samples were collected immediately before surgery (BS) and after surgery (AS) on days 0, 7, 1 month, and 3 months to 1 year. Thirty six patients received ABT and 10 did not. PBMC were isolated and the numbers and % of CD4+CD25+Foxp3+ Tregs and CD4+CD25high/+CD127low/- Tregs were determined by FACS. Tregs and T effectors (Teff) were isolated from patients on days 0-7 and Treg functional assays were performed by culturing Tregs with PHA-stimulated Teff at different ratios for 72h with CFSE, and analyzed by FACS. Cytokine serum level determined with Cytometric Bead Array (CBA) for IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ and ELISA for TNF-α, the receptor TNF-RI(p55/p60) and II(p75/p80), TGF-β1 and β2. Results: Both, natural (CD4+CD25+Foxp3+) and inducible (CD4+CD25high/+CD127low/-) Tregs increased in day 0 and decreased in day 7 until BS levels, after ABT. Opposite results (small reduction) observed in patients without ABT. With functional assays proved that Tregs are functional and suppress the T-cell proliferation. IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, the receptor TNF-RI(p55/p60) and II(p75/p80), TGF-β1 and β2 increased after the surgery, after ABT. IL-6, TNF-RI(p55/p60) and II(p75/p80) levels increased with SSD after the surgery, after ABT. TGF-β1 levels decreased in day 0 until BS levels (Th3 response). Th3 cells growth from CD4+CD25- FoxP3- Th0 peripheral cells. Th3 prevents maturation of DCs, Th2 T-cells. Induce the TGF-β secretion and inhibit IL-2 and antibodies secretion. Conclusion: In patients underwent scheduled joint replacement surgery, Tregs increased after ABT until 1 month and are functional and suppress Teff proliferation under PHA condition. IL-6, TNF-RI and TNF-RII are activation markers of immune system and suppressed after ABT. In day 0, IL-6, TNF-RI and II levels increased as a reaction graft against host’s antigen. After surgery (day 0), patients develop Th1 response and Tregs proliferation, after ABT. Gradually, Tregs suppress the proinflammatory responses until the balance in the recipient, after the surgery.

Red blood cells are a scarce resource whose demand often exceeds its supply. Intraoperative red cell salvage has proven to be a highly effective blood conservation strategy, as it can reduce the need for allogeneic blood transfusion. However, the use of cell saver alone is not sufficient. Without specific blood ordering guidelines, the amount of allogeneic blood product requested and cross&ndash;matched is often much greater than the real level of consumption. Efficient blood ordering guidelines have been developed in the past, and have succeeded in providing a more accurate prediction of actual need for intraoperative blood transfusion and minimizing waste. Few studies attempted to examine the blood ordering and utilization pattern with an emphasis on surgical cases that involve the use of intraoperative cell salvage. With the use of intraoperative cell salvage devices to reduce the amount of blood bank products required during surgery, considerable change in the practice of ordering cross&ndash;matched blood should be made. We retrospectively assessed the effectiveness of one Standardized Clinical Assessment and Management Plan (SCAMP) in improving the efficiency of blood utilization and reducing waste. This SCAMP was introduced at our Boston Children's Hospital in July 2012 as a blood ordering guideline for all pediatric orthopedic patients who are scheduled for intraoperative cell salvage. We retrospectively compared demographic variables, clinical characteristics, and blood utilization patterns of patients who underwent orthopedic procedure and received cell saver blood during the 17 months prior to the introduction of SCAMP (n = 455) and those who underwent similar procedures during the 15 months after the introduction of SCAMP (n = 487). Results suggested that demographic variables including age, weight, and sex were similar between the pre&ndash;SCAMP and post&ndash;SCAMP groups. It also demonstrated that after the introduction of SCAMP, the mean percentage utilization of blood (number of units used/number of units ordered x 100%) increased by 24.4% (p < 0.001), while the difference between the number of units ordered and number of units used reduced by 0.5 units (p < 0.001). In conclusion, the introduction of a SCAMP for blood product ordering has led to an increase in the efficiency of blood utilization and a reduction in blood waste. However, further evaluation and modification of the SCAMP need to be made in order to better predict actual level of utilization of blood products.

Orientador: Elenice Deffune / Resumo: A Coordenação Geral de Sangue e Hemoderivados CGSH, do Ministério da Saúde, comprometida com a missão de elaborar políticas que promovam o acesso da população à atenção hematológica e hemoterápica de forma segura e com qualidade, desenvolve suas ações em consonância com os princípios e as diretrizes do Sistema Único de Saúde – SUS e através da ANVISA implantou em 2001 a Avaliação Externa da Qualidade em Imuno-hematologia (AEQIH) contando com 8 unidades produtoras (UP). Em 2005 o Hemocentro de Botucatu passou a integrar as UP. Este trabalho tem como objetivo avaliar o desempenho dos serviços de hemoterapia (SH) da área de abrangência da Grande São Paulo, sob responsabilidade da UP de Botucatu no período de 2005-2015 levando em consideração diferentes indicadores: número de serviços atendidos/índice de adesão; erros e acertos nas técnicas de tipagem ABO e RhD, pesquisa de anticorpos irregulares (PAI), identificação de anticorpos irregulares (IAI), teste da antiglobulina direta (TAD), prova cruzada (PC) e fenotipagem eritrocitária (FE). A análise estatística realizada foi a de regressão linear, teste de correlação de Spearman e Curva ROC. Durante os 10 anos foram enviados 29 painéis práticos contendo 4 tipagens ABO e RhD (n=10.382), 2 amostras para PAI, IAI e TAD (n=5.191 respectivamente), PC (n=1.611) e FE (n=1.074) e 21 avaliações teóricas (18.975 questões). A média de SH participantes durante o período determinado foi de 89,5. O índice de crescimento, levando em considera... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre