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By contributing new knowledge to a particular area of science, the publication of scientific articles is the primary objective of research projects and of the researcher. The systematic planning of a project, obedience to every step of the research protocol makes sure that the results found, whether relevant or not, are accepted by the scientific community. The result of this work will always be the publication of a scientific paper. Afterwards the author submits his contribution to a peer-reviewed scientific journal, either within his field or to a more prestigious journal, for publication. In several editorials, the Revista Brasileira de Hematologia e Hemoterapia (RBHH) has discussed the Qualis classification system of the Coordenacao de Apoio aos Profissionais do Ensino Superior (CAPES) and its effects on the Brazilian academic community(1,2). Unhappily this system punishes almost all Brazilian authors but, in particular, those that publish in journals dedicated to their specialty such as the RBHH. As the lay press reported the classification system puts Brazilian scientific journals at "risk of extinction"(3). On the subject of Brazilian scientific journals, editors on several occasions have disagreed with the use of the impact factor of Institute for Scientific Information (ISI) Thomson Reuters JCR to evaluate Brazilian scientific production(4). Moreover, data showing the geometric growth of the number of scientific publications in Brazil and relatively low number of citations of national studies were presented in the last editorial(5). Recently, via the scientific publishers list of the World Association of Medical Editors on the web, journal editors from diverse areas have been condemning cases of plagiarism and duplicate publications(6). Furthermore they criticize the cutting up of data resulting from a single research project with the goal of increasing the number of publications of one specific author or group of authors, a technique that received the facetious name of 'salami science'. Although distinct, articles and texts have recently appeared in the lay press on both these subjects(3,7). The articles about CAPES were not complimentary to this government institution. In fact, discussions about the position of CAPES in respect to the evaluation of scientific production have been circulating in the scientific corridors for a few years now. Debates condemn its policies, but it seems that nothing really changes. One of the major concerns of bureaucrats, who have little or no knowledge of true scientific research, is the need to systematically measure the worth of scientists. How do we decide, for example, whether researchers deserve promotion, pay increases, more political clout or even that grant that they have applied for? To do this, government intuitions around the world are using the number of publications and the impact factor, an index developed to compare journals and not authors. Does this make a difference? This has created the 'Publish or Perish' culture which includes 'Salami Science'. Whether duplicate publications (which the RBHH does not accept) are ethically correct or not can be argued. Although this may waste the reader's time and, for example, distort the overall results of database searches, it seems that there may be ethical support for this practice when the author truly believes that his work will make a difference in the quality of patients' treatment. Certainly publications in different languages should not be frowned upon as most practitioners in non-English speaking countries do not speak English. This is definitely the case of Brazil where even the aforementioned government institution, CAPES, encourages all to publish in English with no importance whatsoever given to the native language. This it does by a points system where articles that are not published in ISI are assigned a very low number of points and only three articles are included in an author's scientific production evaluation. Even articles published in PubMed, for many researchers the preferred source database for research, receives half the points of an article published in the lowest ISI classification. Furthermore, splitting a long arduous paper into simpler parts can be helpful not only to the understanding of readers but also to increase the spread of knowledge. Unfortunately today we are living in a world where people are reading less and less due to culture changes related to the modern way of life. Many individuals, including physicians, are not used to reading complicated articles anymore and either get lost in the middle, lose patience or both and so, many long articles remain relatively unread. Perhaps we should change our opinions on this subject. And this leads me to the most important question - why do we publish? There are numerous reasons but the most common in medicine are to improve patient care, to exchange knowledge with other researchers and to improve academic careers. Of course our egos do not suffer from a good publication too. One imagines that the primary goal of medical publications should be to improve treatment for patients. It seems fairly clear that the best way to achieve this end is to make knowledge widely and freely available to all practitioners, independent as to whether they are university professors, researchers or the ordinary physician in a small town in the middle of nowhere. We know that today the changes in medicine are rapid and that lifelong learning is essential to keep up, but for many this is not possible as the information is not readily available. All researchers would like to publish in journals with the highest impact factors. Of course this, as renowned researchers seek to publish in The Lancet, JAMA, Nature and the New England Medical Journal, perhaps artificially and definitely wrongly, consolidates the position of the elite journals at the top. The reason I suggest this is as follows. As initially the ISI, the fore runner of Thompson Reuters, the 'owner' of the Impact Factor, only included journals published in English, this gave the North American and British journals a head start, they had impact factors before any 'foreign' journal even thought about publishing in English. As the impact factor became important to their careers, 'top' researchers obviously invested in trying to publish in these journals. Moreover, the Lancet, JAMA, Nature and the New England Medical Journal are journals that cover all fields in medicine. This gives them a much greater opportunity of finding articles that they believe will be cited. However, for most everyday practitioners, these 'elite' journals are not the first choice. Most practitioners want all the information in one place, concentrated and at a low cost (or free) and therefore subscribe to a journal of their specialty. Hence, it seems that most authors who submit to these 'top name journals' perhaps do so, not to spread knowledge to improve the health of the population, but for their own careers. With the attitude of CAPES can we blame them? Even HINARI, the Access to Research Initiative, in which the RBHH participates, started in 2002 by the WHO and major publishers, although a very good start, has its flaws as only medical and nursing schools, universities and research institutions in developing countries have access and not to all journals(8). After a physician leaves medical school, is he no longer entitled to have access to new advances in medicine? But perhaps the solution to this problem is around the corner. Until now many articles are published in more than one database (SciELO, PubMed, ISI and in smaller databases) and also in the site of the journal itself. This distorts any calculation of the impact factor and limits it only to articles published in ISI. With the creation of the digital object identifier (DOI) the next logical step is to create a new manner to really identify the importance of scientific publications that is independent of the database or databases in which an article is 'published'. Furthermore, with the simplicity of analysis using the World Wide Web, all articles can be broken down to their source articles giving all due respect to the real discoverer of new knowledge and not just to the people who report it in review articles.

Made available in DSpace on 2015-12-07T15:35:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2015. Added 1 bitstream(s) on 2019-10-09T18:24:49Z : No. of bitstreams: 1 S1516-84842015000200120.pdf: 1620399 bytes, checksum: facf6c813e5a774eb53361208d0c4cad (MD5) This review discusses hemoglobin D-Punjab, also known as hemoglobin D-Los Angeles, one of the most common hemoglobin variants worldwide. It is derived from a point mutation in the beta-globin gene (HBB: c.364G>C; rs33946267) prevalent in the Punjab region, Northwestern Indian. Hemoglobin D-Punjab can be inherited in heterozygosis with hemoglobin A causing no clinical or hematological alterations, or in homozygosis, the rarest form of inheritance, a condition that is commonly not related to clinical symptomatology. Moreover, this variant can exist in association with other hemoglobinopathies, such as thalassemias; the most noticeable clinical alterations occur when hemoglobin D-Punjab is associated to hemoglobin S. The clinical manifestations of this association can be similar to homozygosis for hemoglobin S. Although hemoglobin D-Punjab is a common variant globally with clinical importance especially in cases of double heterozygosis, hemoglobin S/D-Punjab is still understudied. In Brazil, for example, hemoglobin D-Punjab is the third most common hemoglobin variant. Thus, this paper summarizes information about the origin, geographic distribution, characterization and occurrence of hemoglobin D-Punjab haplotypes to try to improve our knowledge of this variant. Moreover, a list of the main techniques used in its identification is provided emphasizing the importance of complementary molecular analysis for accurate diagnosis. Universidade Estadual Paulista (UNESP), São José do Rio Preto, SP, Brazil. Electronic address: lidiane.unesp@gmail.com. Universidade Estadual Paulista (UNESP), São José do Rio Preto, SP, Brazil. Universidade Estadual Paulista (UNESP), São José do Rio Preto, SP, Brazil. Electronic address: lidiane.unesp@gmail.com. Universidade Estadual Paulista (UNESP), São José do Rio Preto, SP, Brazil.

ObjectiveTo report on the use of chronic myeloid leukemia as a theme of basic clinical integration for first year medical students to motivate and enable in-depth understanding of the basic sciences of the future physician.MethodsDuring the past thirteen years we have reviewed and updated the curriculum of the medical school of the Universidade Estadual de Campinas. The main objective of the new curriculum is to teach the students how to learn to learn. Since then, a case of chronic myeloid leukemia has been introduced to first year medical students and discussed in horizontal integration with all themes taught during a molecular and cell biology course. Cell structure and components, protein, chromosomes, gene organization, proliferation, cell cycle, apoptosis, signaling and so on are all themes approached during this course. At the end of every topic approached, the students prepare in advance the corresponding topic of clinical cases chosen randomly during the class, which are then presented by them. During the final class, a paper regarding mutations in the abl gene that cause resistance to tyrosine kinase inhibitors is discussed. After each class, three tests are solved in an interactive evaluation.ResultsThe course has been successful since its beginning, 13 years ago. Great motivation of those who participated in the course was observed. There were less than 20% absences in the classes. At least three (and as many as nine) students every year were interested in starting research training in the field of hematology. At the end of each class, an interactive evaluation was performed and more than 70% of the answers were correct in each evaluation. Moreover, for the final evaluation, the students summarized, in a written report, the molecular and therapeutic basis of chronic myeloid leukemia, with scores ranging from 0 to 10. Considering all 13 years, a median of 78% of the class scored above 5 (min 74%–max 85%), and a median of 67% scored above 7.ConclusionChronic myeloid leukemia is an excellent example of a disease that can be used for clinical basic integration as this disorder involves well known protein, cytogenetic and cell function abnormalities, has well-defined diagnostic strategies and a target oriented therapy.

Many articles have been published on the subject of FNAFNA, highlighting the usefulness of flow cytometry in the diagnosis and classification of lymphomas. But occasionally, flow cytometric evaluation fails to detect an abnormal population in a FNAFNA specimen involved by lymphoid neoplasm. Sampling errors (poor viability, peripheral blood contamination and hypocellular specimens) are the major reasons of this failure. In our laboratory we use a simple, fast and cost-effective approach to assess adequacy of FNAFNA materials and in this paper, we describe this procedure with giving some examples of interpretations of our results.

A anemia por deficiência de ferro representa desordem nutricional de maior prevalência em todo o mundo. As duas causas mais comuns de anemia na gestação e pós-parto são a deficiência de ferro e as perdas sanguíneas agudas. Na gestação, as mudanças fisiológicas podem dificultar o diagnóstico das doenças hematológicas. O propósito deste estudo é revisar a deficiência de ferro na gestação, as consequências adversas materno-fetais, o diagnóstico e manejo da anemia na gestação.Iron-deficiency anemia is a highly prevalent nutritional disorder in the whole world. The two most common causes of anemia in pregnancy and in the puerperium are iron deficiency and acute blood loss. Pregnancy is associated with physiological changes that may complicate the diagnosis of hematologic diseases. The purpose of this paper is to provide a brief overview of iron deficiency in pregnancy, adverse maternal-fetal consequences, screening and clinical management of anemia during pregnancy.

Neste trabalho, foram revisadas a literatura internacional e a experiência nacional com transplante de células-tronco hematopoéticas (TCTH) para doenças autoimunes. A evidência acumulada indica que o TCTH autólogo pode beneficiar pacientes com esclerose múltipla em fase inflamatória, refratária aos tratamentos medicamentosos disponíveis, e pacientes com esclerose sistêmica cutânea difusa de caráter progressivo, com ou sem comprometimento sistêmico. Esse tratamento deveria ser disponibilizado na rede pública de saúde, numa fase inicial, em centros de referência com experiência em TCTH e no manejo clínico de doenças autoimunes sistêmicas graves.In this paper, international literature and national experience on hematopoietic stem cell transplantation (HSCT) for autoimmune diseases were reviewed. Cumulative evidence indicates that autologous HSCT may benefit patients with inflammatory multiple esclerosis, refractory to available drug therapy, and progressive forms of diffuse cutaneous systemic sclerosis with or without systemic involvement. Initially, this treatment should be available in reference centers of the public health system, with experience in performing HSCT and in treating severe systemic autoimmune diseases.

As diretrizes apresentadas neste trabalho foram elaboradas e aprovadas na I Reunião de Diretrizes Brasileiras em Transplante de Células-Tronco Hematopoéticas (TCTH) realizada no Rio de Janeiro, entre os dias 19 e 21 de julho de 2009. O evento foi promovido pela SBTMO (Sociedade Brasileira de Transplante de Medula Óssea). Neste artigo, tratamos da anemia aplásica severa (AAS), considerada uma urgência hematológica, que, identificada e manejada de forma precoce, apresenta grande possibilidade de recuperação da hematopoese seja através de transplante de medula óssea ou terapia imunossupressora. Objetiva-se nortear o manejo terapêutico no contexto do transplante e indicar formas de condicionamento, de acordo com as características clínicas dos pacientes, como o número de transfusões, com intuito de minimizar a rejeição primária e secundária, garantindo a melhora da sobrevida global e livre de doença (observadas pela literatura e já validadas por resultados na população brasileira). No que concerne à anemia de Fanconi, o transplante é a única modalidade curativa para o componente aplásico de medula óssea; embora não modificando as outras características da síndrome também demanda perícia e agilidade na busca de um doador com resultados expressivos de sobrevida.The guidelines presented in this article have been prepared and approved in the I Meeting of Brazilian Guidelines in Hematopoietic Stem Cell Transplantation (HSCT) - Rio de Janeiro, July 19-21, 2009. The event was sponsored by SBTMO (Brazilian Society of Bone Marrow Transplantation). In this paper, we treat the severe aplastic anemia (SAA), considered a hematological emergency, that when identified and medically treated early, shows a great chance of recovery of the hematopoiesis, either through bone marrow transplantation or immunosuppressive therapy. Its objective is to guide the management of the transplantation, and indicate methods of conditioning, according to clinical characteristics of each patient, including the number of transfusions, in order to minimize the primary and secondary rejection, ensuring better overall and disease-free survival observed in literature and already validated by the results in our population. In the Fanconi Anemia, transplantation is the only curative option for the aplastic bone marrow component, although insignificant for the other components of the syndrome, it also requires skill and agility in finding a donor with important results.

As síndromes mieloproliferativas crônicas, atualmente denominadas neoplasias mieloproliferativas (NMP), de acordo com a 4ª. edição da classificação da Organização Mundial da Saúde (OMS), são doenças clonais de célula-tronco hematopoética, nas quais há a proliferação aumentada de uma ou mais das séries mieloides (granulocítica, eritrocítica, megacariocítica ou mastocítica) com maturação eficaz. A progressão de todas é caracterizada por fibrose medular ou transformação leucêmica. Pela classificação da OMS, as NMP incluem: leucemia mieloide crônica (LMC), policitemia vera (PV), mielofibrose idiopática crônica (MF), trombocitemia essencial (TE), leucemia neutrofílica crônica (LNC), leucemia eosinofílica crônica não especificada(LEC), mastocitose (M) e neoplasia mieloproliferativa inclassificável (NMI). É interessante notar que tanto a LMC (BCR/ABL1) como PV, MF e TE (JAK2 V617F e éxon 12, MPLW515L/K) e M (KITD816V) tiveram suas bases moleculares desvendadas e apresentam em comum a ativação constitutiva de tirosino-quinase graças às mutações adquiridas pela célula-tronco hematopoética. A mutação JAK2 V617F é observada em mais de 90% dos casos de PV, mas também em cerca de 50%-60% das MF e TE, levando ao questionamento de como uma única lesão molecular desencadeia três manifestações clínicas diversas. Já há evidências de que eventos genéticos e epigenéticos adicionais contribuem para a patogênese, tais como MPLW515L e MPLW515K. No presente manuscrito são apresentados os aspectos clínicos, a fisiopatologia e os critérios diagnósticos das diferentes NMP.Chronic myeloproliferative disorders, currently called myeloproliferative neoplasms (MPN), according to the 4th edition of the World Health Organization (WHO) classification are clonal diseases of hematopoietic stem cells, in which there is increased proliferation of the myeloid series (granulocytic, erythrocytic, megakaryocytic series or mast cells) with effective maturation. The progression of all is characterized by marrow fibrosis or leukemic transformation. According to the WHO classification, the MPNs include: chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), idiopathic myelofibrosis (IM), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia not otherwise categorized (CEL-NC), mastocytosis (M) and myeloproliferative neoplasm unclassifiable (MPNU). It is worth noting that the molecular basis of CML (BCR/ABL1), as well as PV,ET, IM (JAK2V617F and exon 12, MPL W515L/K) and M (KITD816V) have been identified and have, in common, constitutive activation of tyrosine kinase due to acquired hematopoietic stem cell defects. The JAK2V617F mutation is observed in around 90% of PV cases and in around 50-60% of IM and ET leading to the question why a single molecular lesion induces three different clinical manifestations. There is already evidence that additional genetic and epigenetic events contribute to the pathogenesis, including MPL W515L/K mutation. Some clinical aspects, the pathophysiology and diagnostic criteria of MPNs are presented in this paper.

O eritrovírus infecta células precursoras eritroides, determinando a interrupção temporária da eritropoese. Neste contexto, é importante o conhecimento das principais doenças hematológicas que podem estar associadas à presença do vírus, principalmente quando estão presentes em condições mórbidas, tais como nas anemias hemolíticas hereditárias. Este trabalho tem como objetivo relatar as principais doenças hematológicas que cursam com a infecção pelo eritrovírus B19.Erythroviruses infect precursor erythroid cells, determining a temporary disruption of erythropoiesis. Thus, knowledge of the main hematological diseases that may be associated with the virus is important, especially when they are present in morbid conditions, such as in hereditary hemolytic anemia. This paper aims at reporting the main hematological diseases that are associated with erythrovirus infections.

O Instituto Nacional de Controle de Qualidade em Saúde - INCQS, unidade técnico-científica da Fundação Oswaldo Cruz - Fiocruz, desempenha seu papel no controle de qualidade pericial, de bens e serviços sujeitos ao regime de Vigilância Sanitária, em particular medicamentos denominados de hemoderivados. Este trabalho fundamentou-se na análise de 3.100 lotes de hemoderivados, no período de janeiro de 2000 a dezembro de 2004, assim distribuídos: 31,6% (n=980) de albumina humana, 28,7% (n=890) de fator VIII, 21,4% (n=662) de imunoglobulina humana, 8,3% (n=257) de fator IX, 7,1% (n=220) de imunoglobulinas específicas como anti-Rho (D), antitetânica, anti-rábica, anti-Hepatite B e antivaricela zoster e 2,9% (n=91) de complexo protrombínico. As amostras foram recebidas para análise oriundas dos segmentos: portos, aeroportos e fronteiras de Brasília, Rio de Janeiro e São Paulo e de apreensões realizadas pelos estados de Pernambuco, Santa Catarina, Rio de Janeiro e Rio Grande do Sul. Quanto à modalidade de análise: 92,3% correspondem à análise controle, 5,9% fiscal, 1,4% orientação e 0,4% análise prévia. Da internalização dos hemoderivados importados: 40,0% ocorreram pelo aeroporto de Brasília, 26,9% por São Paulo e 25,2% pelo Rio de Janeiro. Concluindo, dos lotes de hemoderivados analisados, 99,1% apresentaram resultados satisfatórios e 0,9% foram insatisfatórios quanto ao ensaio de inspeção visual, solubilidade, ensaio de estabilidade e químico, e quanto ao teste de pirogênio e toxicidade inespecífica. Desta forma, monitorar a qualidade dos produtos hemoderivados é um instrumento fundamental no exercício das ações de Vigilância Sanitária.The technical scientific unit of the National Institute of Quality Control in Health (INCQS), part of the Oswaldo Cruz Foundation, has a role of investigational quality control of products and services related to health surveillance, in particular medicines denominated plasma derivative products. This paper is based on the analysis of the 3100 plasma derivative products from January 2000 to December 2004: 31.6% (n=980) of human albumin, 28.7% (n=890) of factor VIII, 21.4% (n=662) of human immunoglobulins, 8.3% (n=257) of factor IX, 7.1% (n=22) of specific immunoglobulin classes containing anti-Rho (D) immunoglobulin, anti-hepatitis B, anti-tetanus, anti-rabies and anti-varicella-zoster and 2.91% (n=91) of prothrombin complex. The products submitted to analysis came from airports and frontiers of Brasília, Rio de Janeiro and São Paulo, and products confiscated by the states of Pernambuco, Santa Catarina, Rio de Janeiro and Rio Grande do Sul. The type of analysis was characterized as: 92.3% control analysis; 5.9% fiscal analysis; 1.4% guidance and 0.4% preliminary analysis. In respect to imported plasma derivatives, 40.0% originated from the airport in Brasilia, 26.9% in São Paulo and 25.2% in Rio de Janeiro. In conclusion, 99.1% of the plasma derivative products analyzed was considered satisfactory and 0.9% unsatisfactory as identified by visual inspection, solubility, stability and chemical assays and pyrogenic and unspecific toxicity tests. Thus, the assessment of the quality of plasma derivative products is an essential tool for health surveillance.

O sangue de cordão umbilical e placentário (SCUP) é uma rica fonte de células-tronco (CT) hematopoéticas e é amplamente utilizado como substituto da medula óssea em casos de transplante. As células do SCUP possuem vantagens sobre as células da medula óssea (MO), principalmente por serem mais jovens e apresentarem maior taxa proliferativa. Além dos progenitores hematopoéticos, o sangue de cordão umbilical contém progenitores endoteliais e mesenquimais, sugerindo sua possível aplicação nos novos protocolos de terapia celular para diferentes tecidos. Na presente revisão, discutimos a importância do armazenamento do sangue de cordão umbilical autólogo e as pesquisas desenvolvidas para a sua aplicação em doenças degenerativas.Umbilical Cord Blood is a rich source of hematopoietic stem cells widely used as a substitute of bone marrow (BM) in transplants. Cells from umbilical cord blood present advantages over BM cells, mainly as they are younger and a have higher proliferative rate. Besides hematopoietic stem cells, umbilical cord blood contains endothelial and mesenchymal progenitor cells, suggesting their possible application in cell therapy protocols for different tissues. In this paper, we discuss the importance of autologous umbilical cord blood storage and the research on stem cell transplantation for degenerative diseases.

A medicina transfusional tem como objetivo garantir a qualidade e quantidade do sangue, componentes e serviços oferecidos à comunidade, e, dentro desse contexto, a análise dos reagentes imuno-hematológicos é crítica para a realização dos testes pré-transfusionais e, consequentemente, uma transfusão segura. É responsabilidade do controle de qualidade o constante aperfeiçoamento de testes que analisam a qualidade dos reagentes e equipamentos utilizados. Esse trabalho tem por objetivo apresentar os resultados alcançados em dez anos de experiência do Departamento de Controle de Qualidade em Imuno-hematologia da Fundação Pró-Sangue / Hemocentro de São Paulo. No período de janeiro de 1997 a dezembro de 2007 foram realizadas análises em 3.417 reagentes imuno-hematológicos por ocasião da aquisição do reagente e por solicitação de reavaliação (durante o uso). As análises incluíram desde a inspeção visual no recebimento a testes laboratoriais específicos para cada tipo de reagente. Dos 3.417 lotes analisados (média=310/ano, mediana=252/ano), 94 (2,7%) foram reprovados (média=8,54/ano, mediana=7,00 ± 7,79/ano). Uma vez aprovado pelo controle de qualidade à aquisição, nenhum reagente imunohematológico foi reprovado durante o uso desde 2004. Podemos concluir que, para implementação de um sistema de controle de qualidade de reagentes imuno-hematológicos, não é necessário uso de reagentes ou equipamentos altamente especializados, pois os mesmos são utilizados na rotina laboratorial, como também não envolvem alta complexidade na execução das análises. Podemos enfim considerar que a implementação do controle de qualidade em Imuno-hematologia contribui para o aumento da segurança transfusional e é factível de realização nos mais diferentes níveis de complexidade dos serviços hemoterápicos.Transfusion medicine has the purpose of guaranteeing the quality and quantity of blood, blood derivatives and services offered to the community. Thus, the analysis of serological reagents is critical in pre-transfusion testing and, consequently, reliable transfusions. A constant improvement in the tests that analyze the quality of reagents and equipment utilized is the responsibility of quality control. This paper aims at presenting the results and experience achieved over 10 years in the Department of Quality Control in Immunohematology at Fundação Pró-Sangue / Hemocentro de São Paulo. In the period of January 1997 to December 2007 we carried out analyses of 3,417 serological reagents at acquisition and/or during their use. The analyses included from visual inspection to specific laboratory tests for each kind of reagent. Of the 3,417 lots analyzed (mean = 310/year, median = 252/year), 94 (2.7% - median=8.54/year) failed the tests. From 2004 to date, once the reagents were approved, none failed during use. The implementation of a quality control system with standardized techniques is important for the adequate utilization of serological reagents. This system accomplished by retroactive control of the reagents, contributed to the safety and reliability of results in immunohematology testing.

A leucemia de células T no adulto (ATL) é causada pelo vírus linfotrópico de células T (HTLV-1). Contudo, apenas 2%-5% dos indivíduos infectados desenvolvem a ATL e somente 40-60 anos após a infecção. Um fator de risco para adquirir a doença é a via da transmissão do vírus pela amamentação e durante o parto, sugerindo que a criança já é portadora do vírus. Desde a descoberta do vírus, em 1980, vários artigos científicos foram publicados descrevendo as manifestações clínicas, biologia do vírus e alterações intracelulares induzidas pelo vírus. Esta revisão visa explorar alguns aspectos da relação entre HTLV-1 e a leucemia de células T do Adulto.The human T-lymphotropic virus (HTLV-1) is known to be the etiologic agent of adult T-cell leukemia (ATL). Only 2-5% of infected individuals develop ATL and even then only 40-60 years after infection. One risk factor to develop ATL is the transmission of the virus by breastfeeding and during delivery, suggesting that infants of infected mothers are already carriers of the virus. Since the discovery of the virus in 1980 many scientific papers have been published describing the clinical manifestations, biology of the virus and the intracellular alterations induced by the virus. This review aims to explore some aspects of the relationship between HTLV-1 and ATL.

Accumulation of iron in thalassemia causes organ damage and reduces patient survival due to heart lesions in the second decade of life. Iron deposits are monitored by direct (biopsy) and indirect methods (ferritin) with sequential data being better than isolated measurements. This paper compares two indirect measurements of iron overload; a single hepatic iron concentration (HIC) by magnetic resonance and mean ferritin levels over four years. A retrospective study of 25 patients from the Centro Regional de Hemoterapia in Ribeirão Preto, Brazil was carried out. High HIC (above 7 mg per gram of dry weight) was found in 20 patients and high mean serum ferritin (above 2500 μg/L) in 10 patients. Stratification into three levels (low, moderate and high) of iron overload gave similar results in both tests. Many other factors influence de degree of iron overload in thalassemia. No correlation was found using a non-parametric statistical test between HIC and mean serum ferritin. Both methods provide better planning of chelation therapy.O acúmulo de ferro na talassemia causa lesões orgânicas e reduz a sobrevida do paciente por lesão cardíaca na segunda década da vida, e tem sido avaliado por medidas diretas (biópsia) e indiretas (ferritina). As medidas isoladas carecem de valor, sendo preferidas as sequenciais. Este trabalho pretende comparar medidas indiretas de sobrecarga de ferro, uma medida da concentração de ferro hepático por ressonância magnética, e a ferritina sérica média dos últimos quatro anos. Trata-se de estudo retrospectivo de 25 pacientes do Centro Regional de Hemoterapia, em Ribeirão Preto, Brasil. Encontrou-se em vinte pacientes ferro hepático acima de 7 mg/g peso seco e ferritina média elevada acima de 2.500 ug/l em dez. Estratificação em três níveis de sobrecarga (leve, moderada e grave) produziu resultados semelhantes em ambos os testes. Vários outros fatores influenciam o grau de sobrecarga de ferro na talassemia. Não houve correlação significativa com aplicação de testes não-paramétricos. Ambos os métodos usados concomitantemente levarão a um melhor planejamento da terapia quelante.

The introduction of the BCR-ABL kinase inhibitor, imatinib mesylate (Gleevec®, Novartis) led to significant changes in the treatment of chronic myeloid leukaemia (CML) patients. However, despite the impressive percentage of responding patients, some CML cases, particularly those in advanced phases of the disease, show primary resistance or relapse after the initial response. The second-generation BCR-ABL inhibitors nilotinib (Tasigna®, Novartis) and dasatinib (Sprycel®, Bristol-Myers Squibb) have shown significant activity in clinical trials in patients who failed imatinib therapy, but these agents are still incapable of inhibiting the T315I mutant of Bcr-Abl and present partial activity in advanced phases of CML. The acquired biological notions of the mechanisms of tyrosine kinase inhibitor (TKI) resistance has led to the development of new compounds, some of which have shown encouraging preliminary results in clinical trials, even against T315I mutants. In this paper we discuss the new emerging therapies which may overcome TKI resistance in CML patients.A introdução do inibidor de tirosino quinase BCR-ABL mesilato de imatinibe (Glivec®, Novartis) levou a significantes mudanças no tratamento da LMC. Entretanto, a despeito de impressionante porcentagem de pacientes que respondem, alguns casos de LMC, particularmente em fases avançadas da doença mostram resistência primaria ou recidivas após terapêutica inicial. Inibidores de tirosino quinases de segunda geração como o nilotinibe (Tasigna®, Novartis) e o dasatinibe (Sprycel®, Bristol Myers Squibb) têm mostrado significante atividade nos estudos clínicos em paciente onde o imatinibe falhou. Porém, estes agentes não são capazes de inibir a mutação T315I do Bcr-Abl e apresentam atividade parcial em fases avançadas da LMC. As noções biológicas adquiridas sobre os mecanismos de resistência aos inibidores de TK levaram ao desenvolvimento de novos compostos alguns dos quais têm resultados preliminares encorajadores incluindo a mutação T315I. Neste trabalho nós discutimos os novos agentes emergentes e qual o potencial poderão atingir para ultrapassar a resistência aos inibidores de TK em pacientes com LMC.

As gamopatias monoclonais resultam de hiperprodução de um único clone anormal de células plasmocitárias ou linfócitos B. O objetivo da avaliação laboratorial nas gamopatias é demonstrar a presença, a quantidade e o tipo de proteína anormal presente no soro e/ou na urina através do estudo do perfil protéico, quantificação das imunoglobulinas e cadeias leves e avaliação da proteinúria. Este artigo descreve as principais técnicas laboratoriais disponíveis, bem como suas indicações e limitações.Monoclonal gammopathies result from an overproduction of a single abnormal clone of a plasma cell or B lymphocyte. The purpose of the laboratory protocols in these situations is to demonstrate the presence, the characterization and the concentration of an abnormal protein detected in serum and/or urine samples. The laboratory investigation is based on the electrophoretic protein profile, quantification of immunoglobulins, free light chains and proteinuria. This paper describes the major available laboratory methods as well their indications and limitations.

As gamopatias monoclonais constituem um grupo de desordens caracterizado pela proliferação monoclonal de plasmócitos, que produzem e secretam imunoglobulina ou fragmento de imunoglobulina monoclonal (proteína M) . Este artigo propõe uma revisão dos critérios diagnósticos das principais gamopatias monoclonais e diagnósticos diferenciais, uma vez que é comum a sobreposição de muitas características clínicas entre suas variantes. A gamopatia monoclonal de significado indeterminado (MGUS) é definida pela presença de proteína M sérica < 3,0 g/dL e/ou urinária < 1g/24h, infiltração plasmocitária medular menor que 10% e ausência de danos aos órgãos e tecidos. O mieloma múltiplo (MM) assintomático caracteriza-se pela presença de proteína M, infiltração plasmocitária na medula óssea ou em tecido biopsiado e ausência de critérios para MGUS, MM sintomático e plasmocitoma solitário. O MM sintomático é uma neoplasia plasmocitária associada à proteína M sérica e/ou urinária, infiltração medular por plasmócitos e presença de dano orgânico relacionado: hipercalcemia, insuficiência renal, anemia e lesões ósseas. Se a proteína M não é detectada (MM não secretor), a plasmocitose medular precisa ser > 30% ou plasmocitoma documentado por biópsia. Se a lesão óssea decorre de plasmocitoma solitário ou somente osteoporose, sem fratura, a plasmocitose medular também precisa ser > 30%, para preencher critérios de MM. As gamopatias monoclonais podem estar associadas a diversas doenças, incluindo desordens linfoproliferativas, reumatológicas, neurológicas, dermatológicas e infecciosas. A definição das características clínicas e laboratoriais de cada entidade, maligna ou benigna, facilita o diagnóstico das gamopatias monoclonais e, como conseqüência, seu manejo clínico pelos médicos assistentes.Monoclonal gammopathies are a group of disorders characterized by proliferation of monoclonal plasma cells, which produce and secrete monoclonal immunoglobulin or fragments of monoclonal immunoglobulin (M protein). This paper proposes to review diagnostic criteria of the most important monoclonal gammopathies and their differential diagnosis, because superposition of many clinical characteristics is common between variants. The monoclonal gammopathy of undetermined significance (MGUS) is defined by the presence of serum M protein < 3g/dL and/or urinary M protein < 1g/24h, bone marrow plasma cell < 10%, and absence of organ and tissue damage. Asymptomatic multiple myeloma (MM) is characterized by the presence of M protein, bone marrow or tissue biopsy plasma cell infiltration, and non-compliance of the criteria for MGUS, symptomatic MM and solitary plasmacytoma. Symptomatic MM is a plasma cell neoplasm associated with serum or urinary M protein, bone marrow or tissue biopsy plasma cell infiltration and related organ or tissue damage: elevated calcium levels, renal insufficiency, anemia and bone lesions. If no M protein is detected (nonsecretory MM), then at least 30% monoclonal bone marrow plasma cell infiltration and/or a biopsy-proven plasmacytoma is required for MM diagnosis. If a solitary (biopsy-proven) plasmacytoma or osteoporosis (without fractures) are the sole defining criteria, then at least 30% plasma cells are required in the bone marrow for MM diagnosis. Monoclonal gammopathies may be associated with many different diseases, including lymphoproliferative disorders, connective tissue disorders, neurologic, dermatologic and infectious diseases. The clinical and laboratorial characteristics should be very well defined in each variant, malign or benign, easily determining the diagnosis of monoclonal gammopathies and then their clinical management.

Atualmente, um dos maiores problemas na triagem sorológica de doadores de sangue para doença de Chagas é a alta freqüência de reações indeterminadas, o que faz com que muitos indivíduos sadios sejam rotulados como portadores de uma doença grave. O presente trabalho tem o objetivo de analisar o comportamento sorológico para doença de Chagas dos doadores do Hemocentro Regional de Uberaba, MG e propor mecanismos para reduzir o índice de inaptidão sorológica para essa doença. Através de estudo retrospectivo, foi analisado o resultado sorológico de 79.729 amostras obtidas de doações de sangue realizadas neste Serviço entre janeiro de 2000 e dezembro de 2004. Os resultados foram analisados quanto às variáveis: tipo de doador (novo e de retorno), gênero e idade (inferior ou igual a 30 anos e superior a 30 anos). Para a análise estatística foram realizados os testes do Qui-Quadrado e de comparação de proporções (Z). A ocorrência de doações com sorologia não negativa para doença de Chagas entre doadores novos foi significativamente superior aos de retorno, com p< 0,0001. Quanto à idade, a proporção de positivos no grupo maior de 30 anos foi significativamente superior à do grupo com idade igual ou inferior a 30 anos (p< 0,0001). O elevado número de reações indeterminadas nesse Serviço está de acordo com estudos recentes, reforçando a necessidade da implementação de testes sorológicos 100% específicos ou de exames confirmatórios práticos e rápidos, passíveis de serem introduzidos nas rotinas dos serviços de hemoterapia, reduzindo o descarte desnecessário de bolsas de sangue.Currently one of the major problems in the serological selection of blood donors in respect to Chagas' disease is the high incidence of indeterminate reactions, making a large number of healthy individuals incorrectly diagnosed as seriously ill. This paper aims at evaluating the serological pattern of Chagas' disease of donors of the Uberaba Blood Center and also to propose mechanisms to reduce the rate of serological ineligibility due to suspicion of this disease. A retrospective study of the serological results of 79,729 samples of blood was carried out between January 2000 and December 2004. The results were analyzed according to the following variables: type of donor (first-time and multiple), gender and age (less than or equal to 30 or more than 30 years old). The statistical analysis was made using the chi-square test and a comparison of proportions (Z). Indeterminate results in respect to Chagas' disease among first-time donors were significantly higher than those of multiple donations with p < 0.0001. As for age, the proportion of positivity in the over 30-year-old group was significantly higher to that of the under or equal to 30-year-old group (p < 0.0001). The high number of indeterminate reactions at this center is in accordance with recent studies, highlighting the need of implementing serological tests with 100% specificity or the use of practical and fast confirmation tests to be routinely introduced in hemotherapy services, reducing the unnecessary rejection of blood bags.

Muitos fatores são responsáveis pela diversidade de sintomas nos pacientes de anemia falciforme, entre eles: sexo, idade, haplótipos e nível de hemoglobina fetal. O objetivo deste estudo foi verificar a diversidade clínica e laboratorial dentro do haplótipo bantu. Realizou-se um estudo descritivo onde foram avaliados 18 crianças e adolescentes portadores de anemia falciforme e homozigóticos para o haplótipo bantu, relacionando sexo e idade com as características clínicas e laboratoriais, além de relacioná-las diretamente entre si. As amostras foram do tipo casuais simples. O tamanho da amostra teve uma variação de freqüência para o evento de 30% a 65% e nível de confiança de 99,9%. As análises estatísticas foram realizadas através do programa EPIINFO, versão 6.04b, com erro a de 5%. A faixa etária de 01 a 11 anos teve um maior número de infecções que a faixa de 12 a 19, além de níveis mais altos de hemoglobina fetal. Os valores do hematócrito foram maiores no sexo feminino. Níveis mais elevados de hemoglobina A2 foram relacionados com maior número de infecções, enquanto níveis mais elevados de hemo­globina fetal foram relacionados com maiores valores de hematócrito e menor número de crises álgicas/ano de acompanhamento. O número de transfusões/ano teve correlação positiva com o número de crises álgicas, de infecções e de inter­namentos. Este estudo sugere que há uma diversidade clínica e laboratorial dentro do haplótipo bantu e possivelmente está relacionado com o sexo, a idade e os níveis de hemoglobina fetal e A2 dos pacientes.Several factors have been identified as possibly being responsible for the diversity of sickle cell anemia patients’ symptoms, including gender, age, haplotypes and hemoglobin F levels. The aim of this paper is to verify the clinical and laboratorial diversity of the Bantu haplotype. A descriptive study was performed of eighteen children and adolescents with sickle cell anemia and homozygous for the Bantu haplotype. Gender and age were assessed in respect to clinical and laboratorial features. Statistical analysis of the results was achieved using the EPIINFO program version 6.04. Children from 1 to 11 years old had more infections than adolescents from 12 to 19 and higher levels of hemoglobin F. The hematocrit was higher in girls. Higher levels of hemoglobin A2 were related to more infections, and higher levels of hemoglobin F were related to hematocrit values and lower numbers of infections and periods in hospital. This study suggests that there is diversity within the Bantu haplotype, which is possibly related to gender, age and hemoglobin A2 and hemoglobin F levels of patients.

Infecção é uma freqüente complicação em pacientes com leucemia linfocítica crônica (LLC). O risco de infecção é maior à medida que a doença avança, e guarda estreita correlação com a dosagem de imunoglobulinas no sangue. Embora o defeito imune primário na LLC seja deficiência de imunoglobulinas, as diversas modalidades de tratamento comprometem outros elementos do sistema imune, ampliando o espectro de agentes infecciosos. Este texto sumariza o conhecimento atual sobre os riscos de infecção com as diversas modalidades de tratamento e apresenta recomendações para o manejo destas infecções, seja na prevenção seja no tratamento. Tais recomendações são colocadas em graus de evidência tanto do ponto de vista de sua força quanto da qualidade da evidência.Infection is a frequent complication in patients with chronic lymphocytic leukemia (CLL). The risk of infection is greater with advanced disease and with lower serum immunoglobulin levels. In newly diagnosed patients, the main immunodeficiency is hypogamaglobulinemia, but with different regimens of treatment, other immunodeficiencies occur and contribute to changing the spectrum and increasing the incidence of infection. This paper reviews the current knowledge of the risks and epidemiology of infection according to the different regimens given in the treatment of CLL, and presents recommendations for prophylaxis and treatment of these infections. Such recommendations are rated according to standard scoring schema used in other guidelines to illustrate the strength of the supporting evidence and the quality of the data.

Após a introdução da técnica de antiglobulina indireta por Coombs em meados da década de 40, vários anticorpos antieritrocitários foram descobertos. O grupo sanguíneo Duffy foi descoberto quando Cutbush e Ikin detectaram, no início da década de 50, os primeiros anticorpos desse sistema. Os anticorpos Duffy são clinicamente significantes na prática transfusional, pois mostraram ser causadores de reação hemolítica transfusional e de doença hemolítica do recém-nascido, sendo de ocorrência mundial. O gene FY é constituído por dois exons e seu lócus foi mapeado no cromossomo 1q22-q23. Os antígenos Fyª e Fy b são codificados pelos alelos FYA e FYB e são responsáveis pelos fenótipos Fy(a+b-), Fy(a-b+) e Fy(a+b+). São carreados por uma glicoproteína de 336 aminoácidos também chamada DARC (Duffy Antigen/Receptor for Chemokines), que tem alta afinidade a quimiocinas, sendo também os receptores para Plasmodium vivax. Os polimorfismos relacionados aos seus alelos permitiram o desenvolvimento da técnica de genotipagem por PCR, que é de grande utilidade para a segurança transfusional e incompatibilidade feto-materna. Na última década, inúmeras pesquisas têm sido feitas quanto ao papel biológico dos antígenos de grupos sangüíneos. Nesse artigo iremos revisar o sistema de grupo sangüíneo Duffy, em especial quanto à prática transfusional e suas funções biológicas.After the introduction of the indirect antiglobulin technique by Coombs in the middle of the 1940's, several antibodies have been discovered. Duffy blood group system came to light when Cutbush and Ikin detected the first antibodies related to this system in the beginning of the 1950's. The antibodies of this system are clinically significant in transfusional practice as they have been involved in hemolytic transfusion reactions and hemolytic disease of the newborn, showing them to be of worldwide occurrence. The FY gene is constituted of two exons and its locus was mapped on chromosome 1q22-q23. The Fyª and Fy b antigens are encoded by FYA and FYB alleles, and are responsible for the Fy(a+b-), Fy(a-b+) and Fy(a+b+) phenotypes. They are carried by a 336 amino acid glycoprotein called DARC (Duffy Antigen/Receptor for Chemokines) which has high affinity to chemokines, also being Plasmodium vivax receptors. The polymorphisms related to its alleles have led to the development of a PCR genotyping technique, which is useful for the safety of blood transfusion, and determining fetus-maternal incompatibilities. In the last decade, much research has been done to determine the biological role of blood group antigens. In this paper we reviewed the Duffy Blood Group System, especially in respect to transfusional practice and biological functions.

Com os avanços terapêuticos que incluem o mesilato de imatinibe, o transplante de medula óssea e a infusão de linfócito do doador, a perspectiva de vida dos portadores de leucemia mielóide crônica (LMC) tem aumentado significativamente e a doença pode não ser fatal. No entanto, os mecanismos biológicos que privilegiam a seleção das células hematopoéticas malignas sobre as células normais na LMC, responsáveis pelo insucesso terapêutico em muitos casos, ainda não estão totalmente esclarecidos. Alterações no processo de apoptose celular e escape das células leucêmicas à resposta imune antitumoral poderiam explicar, em parte, a vantagem seletiva dessas células. O processo de apoptose celular pode ser desencadeado pelas vias intrínseca ou extrínseca. A extrínseca é dependente da interação de receptores de morte celular, como a ligação do receptor Fas com seu receptor, o Fas ligante (FasL). A expressão diminuída de Fas e aumentada de FasL na célula leucêmica podem aumentar sua sobrevida tornando-a resistente à apoptose. Esse artigo descreve a relação entre LMC e o sistema Fas/FasL, sua possível importância no prognóstico e escape das células leucêmicas à resposta imune.With therapeutic advances that include imatinib mesylate, bone marrow transplantation and donor lymphocyte infusion, life expectancy of chronic myeloid leukemia carriers has increased significantly and the disease might not be fatal. However, the biological mechanisms that favor the selection of malignant clone cells over normal cells, in most cases responsible for the lack of therapeutic success, are still unclear. Alterations in cellular apoptosis process and escape of the leukemic cells from the anti-tumor immune response can explain, in part, the selective advantages of these cells. The apoptosis process or programmed cell death can be triggered by intrinsic or extrinsic pathways. The extrinsic is dependent on the interaction of cell death receptors, such as the Fas receptor and its agonist, the Fas ligand (FasL). A diminished expression of Fas and increased of FasL in leukemic cell may increase its survival, thereby making it resistant to apoptosis. This paper describes the relation between chronic myeloid leukemia and the Fas/FasL system and its possible importance in prognosis and in escape of the leukemic cells from the immune system.

In the book "Eat Right For Your Type" the author Peter J. D'Adamo writes that the O blood type was the first blood type to appear in humans and affirms that the blood groups are the key to the immune system. Some recent phylogenetic network studies in humans and non-human primates implies that the A gene represents an ancient form of the ABO genes. Relationships between blood groups and infectious and noninfectious diseases and immunodeficiency abnormalities have also been reported in the literature. As D'Adamo's propositions seem to be in opposition with the current knowledge, we present in this paper some comments about the genetics and the evolution of the ABO blood group genes and some links between this blood system and the functioning of the immune system.Peter J. D'Adamo, autor do livro "Eat Right For Your Type", escreve que o grupo O representa o primeiro tipo sangüíneo que surgiu nos humanos e também afirma que os grupos sangüíneos constituem as bases do sistema imune. Recentes estudos filogenéticos realizados em primatas humanos e não humanos estabeleceram que o gene A representa a forma ancestral dos genes que ocupam o locus ABO. Associações entre os grupos sangüíneos ABO, doenças infecciosas, não infecciosas e imunodeficiências também foram relatadas. Diante das proposições do autor, as quais se opõem às informações resultantes de recentes estudos moleculares e filogenéticos, nossa intenção é apresentar algumas reflexões sobre a genética e a evolução dos genes do sistema ABO e as conexões deste sistema com o sistema imune.

A leucemia mielóide aguda (LMA) com diferenciação e t(8;21) ou LMA M2 com t(8;21), pela classificação FAB, tem sido descrita entre 6% e 12% dos casos nas grandes séries. Em nosso meio há poucas descrições com números expressivos de casos. O objetivo do presente trabalho foi avaliar qual a freqüência de t(8;21) dentre 190 casos de LMA, ao diagnóstico. Foram observados 13 (6,8%) casos com t(8;21)(q22;q22), a idade mediana foi de 30 anos (variando de 3 a 64 anos), sendo que seis (46,2%) pacientes tinham menos que 21 anos e relação M:F de 0,8:1 (seis homens e sete mulheres).Acute myeloid leukemia with differentiation and t(8;21) or AML FAB M2 with t(8;21) has been described in from 6% to 12% of the cases in large series. There are very few descriptions with a small number of cases in Brazil. The objective of the present paper is to evaluate the frequency of t(8;21) among 190 cases of AML, at diagnosis. A total of 13 (6,8%) cases with t(8;21) (q22;q22) have been described, with a median age of 30 years (varying from 3 to 64), with six (46,2%) patients younger than 21 years old, and a male to female rate of 0.8:1 (six men to seven women).

This paper describes the tomographic appearance of pulmonary lymphomas. We studied the thoracic computed tomographies of ten patients with biopsy-proven diagnoses non-Hodgkin's and Hodgkin's disease. The most common radiologic findings in this series are the alveolar opacities with air bronchograms (n=8). Other manifestations include multiple pulmonary nodules (n=4), thickening of broncho-vascular bundles (n=3) and foci of ground-glass attenuation (n=2). The present series confirms the results published in available literature about the radiographic appearance of the disease.

Thalassemias are a heterogeneous group of inherited disorders characterized by a microcytic hypochromic anemia and an imbalance in the synthesis of the globin-chains. Hb C is the second most frequently variant of hemoglobin found in Brazil. The laboratory diagnosis of hemoglobinopathies, including thalassemias, is growing in importance, particularly because of an increasing requirement for neonatal diagnosis of abnormal hemoglobins. Screening tests were carried out using alkaline and acid electrophoresis, globin-chain analysis by cellulose acetate in alkaline pH, isoelectric focusing and HPLC. The molecular characterization was made by PCR-ASO for Hb C and beta thalassemia mutants. Large-scale screening and discriminative methodologies must provide information about the hemoglobin polymorphisms in Brazilian population. HPLC is a powerful tool in these cases. Molecular characterization is important to genetic counseling and clinical management, in particular for the Brazilian population that have an intense racial admixture, with great variability of hemoglobins. In this paper an association between Hb C and beta thalassemia (IVS-II-654) in a black family from Brazil was described.

A hemoterapia tem buscado incessantemente o aumento da segurança transfusional. Para tanto tem envolvido, dentre outros, a padronização de testes que comprovem a qualidade dos reagentes utilizados nos serviços hemoterápicos, as análises, o uso e a manutenção de equipamentos apropriados e treinamento de funcionários. O controle de qualidade é essencial e indispensável para a obtenção de resultados confiáveis nos ensaios para os quais se destinam. Até o momento, não há descrição pré-estabelecida dos requisitos mínimos para os reagentes utilizados nos testes imuno-hematológicos pelo Ministério da Saúde. Este trabalho tem por objetivo apresentar os aspectos práticos que envolvem o controle de qualidade em imuno-hematologia, além de informações básicas sobre os principais reagentes imuno-hematológicos disponíveis no mercado brasileiro.One of the main objectives of transfusion medicine is to promote safe transfusion. Continuous improvement involves the standardization of techniques used for quality control of reagents, adequate equipment evaluation and its maintenance and staff training. Quality control of reagents is critical for achieving reliable results in immunohematological testing. In Brazil, as far as we know, there are no minimum requirements for immunohematological reagent guidelines. This paper has the purpose of describing practical aspects of quality control in imunohematology, as well as providing information on the most common immunohematological reagents available on the Brazilian market.

A Portaria do Ministério da Saúde n.º 822/01 regulamentou a triagem neonatal de vários distúrbios metabólicos, incluindo as doenças falciformes e outras hemoglobinopatias. No presente trabalho, os autores comentam vários aspectos médicos e éticos da triagem neonatal das hemoglobinopatias, o aconselhamento genético como parte da responsabilidade médica e os riscos inerentes aos programas populacionais, que merecem ser conhecidos e prevenidos pelos profissionais que atuam na área de triagem neonatal.The government directive MS 822/01 of the Brazilian Ministry of Health, regulates neonatal screening of many metabolic disorders, including sickle cell diseases and other hemoglobinopathies. In the present paper the authors discuss various medical and ethical aspects of neonatal screening for the hemoglobinopathies, the genetic counseling as part of medical responsibilities, and the risks inherent to population programs, which must be known and prevented by the professionals committed to and working in the field of neonatal screening.

A Portaria do Ministério da Saúde n.º 822/01 regulamentou a triagem neonatal de vários distúrbios metabólicos, incluindo as doenças falciformes e outras hemoglobinopatias. No presente trabalho, os autores comentam vários aspectos médicos e éticos da triagem neonatal das hemoglobinopatias, o aconselhamento genético como parte da responsabilidade médica e os riscos inerentes aos programas populacionais, que merecem ser conhecidos e prevenidos pelos profissionais que atuam na área de triagem neonatal. The government directive MS 822/01 of the Brazilian Ministry of Health, regulates neonatal screening of many metabolic disorders, including sickle cell diseases and other hemoglobinopathies. In the present paper the authors discuss various medical and ethical aspects of neonatal screening for the hemoglobinopathies, the genetic counseling as part of medical responsibilities, and the risks inherent to population programs, which must be known and prevented by the professionals committed to and working in the field of neonatal screening.

The neonatal period is considered the most effective for the screening of hemoglobinopathies. This allows prophylaxis and prevention, improving the patient's survival and guidance of parents and heterozygote carriers. The present work aims at the early detection of abnormal hemoglobins, the establishment of standard analysis and to examine the viability of the prevention program. Blood samples were collected by heel stick and from blood cord of children born in the Hospital de Base São José do Rio Preto, from April 1998 to November 1999. Electrophoresis and cytological, biochemical, cromatographic analyses were made for abnormal hemoglobin characterization. A total of 1,478 neonatal blood samples were analyzed in which 14.62% presented with hemoglobins alterations: 3.32% had Hb S; 0.61% had Hb C; 7.44% were suggestive of alpha thalassemia; 1.55% were suggestive of beta thalassemia, and 1.70% had alpha/beta thalassemia interactions. The samples collected from the blood cord showed better results in all analyses while the blood samples collected by heel stick on filter paper, were applicable to only specific methodologies. The routine laboratory methods allowed identification of the thalassemic and variant forms, and isoelectric focusing presented sensitivity only for variant identification in this age range. The suspected cases were reassessed after six months, which permitted genetic counseling of their family members and clinic attendance. A multidisciplinary approach in programs of this kind is fundamental for its success.

In this paper, we discuss the launching of a cooperative protocol of hematopoietic stem cell transplantation for autoimmune diseases in Brazil. We present specific conditions of the country's health system which would affect the trial, preliminary results of the first nine patients transplanted under the protocol (4 systemic lupus, 3 multiple sclerosis, one systemic sclerosis and one overlapping lupus + systemic sclerosis) and future prospectives of organizing phase III randomized trials to answer specific scientific questions pending in the field.Neste trabalho, discutimos a implantação de um protocolo cooperativo de transplante de células tronco hematopoéticas para doenças auto-imunes no Brasil. Apresentamos as condições específicas do sistema de saúde do país que poderiam afetar o projeto, resultados preliminares dos primeiros nove pacientes transplantados (quatro com lúpus sistêmico, três com esclerose múltipla, um com esclerose sistêmica e um com superposição de lúpus com esclerose sistêmica) e perspectivas futuras de organização de estudos randomizados de fase III para responder questões específicas pendentes nesta área.

Inherited disorders of hemoglobin, the most common monogenic disease, are now well understood at the molecular level, knowledge, which has led to considerable improvements in their control and management. The Brazilian population is multiethnic, and the correct characterization of the Hb D is important, mainly because the method available for detection of abnormal hemoglobins, present a migration in the same zone at alkaline pH, for Hb S, D, and G for example. In this paper we studied a family with an abnormal hemoglobin like S in alkaline electrophoresis, by appropriated methods including HPLC and molecular analysis, characterized as hemoglobin D Los Angeles.As doenças hereditária da hemoglobina são as mais comuns doenças monogênicas e atualmente bem conhecidas do ponto de vista molecular, fato este que propiciou um avanço no seu controle e manuseio. A população brasileira caracteriza-se pela multiplicidade étnica e a caracterização da Hb D torna-se importante por este dado, associado ao fato de que os métodos de detecção das hemoglobinopatias comumente não identificam esta fração anormal que apresenta a peculiaridade de migração eletroforéticia em pH alcalino na mesma zona observada nas Hb S e G. Neste relato é apresentado um estudo familiar no qual é empregada metodologia adequada, o HLPC, que permite a identificação da Hb D.

O objetivo deste relato é fazer uma revisão a fim de obter informações atualizadas sobre trombocitopenia induzida por heparina, suas manifestações clínicas, seu diagnóstico e seu manejo terapêutico. Após, concluímos que a trombocitopenia induzida por heparina é uma complicação comum em pacientes submetidos a tratamento com heparina, indiferentemente da doença de base. Complicações trombóticas potencialmente fatais têm sido descritas. Por essa razão, se houver suspeita de trombocitopenia induzida por heparina, uma abordagem adequada incluindo suspensão precoce da heparina é mandatória. Produtos que substituem a heparina incluem hirudina e danaparóide sódico. Heparina de baixo peso molecular é contra-indicada.The aim of this paper is to review current information about the clinical manifestations, diagnosis and management of heparin-induced thrombocytopenia. This was achieved by a bibliographic review using Public Medline and consulting Hematology textbooks. From this study we concluded that heparin-induced thrombocytopenia is a common complication of patients exposed to heparin therapy regardless of underlying conditions. Potentially fatal thrombotic complications have been reported. Therefore, if heparin-induced thrombocytopenia is suspected, an adequate approach including early heparin discontinuation is mandatory. Alternative products for heparin include hirudin and danaparoid sodium. Low-molecular-weight heparin is contraindicated.

Allogeneic Stem Cell Transplantation (ASCT) remains the unique curative therapy for CML in all clinical phases of the disease. However, the results of Imatinib Mesilate (IM) therapy are sufficiently impressive to have displaced ASCT to second- or third-line treatment depending on the availability of newly developed tyrosine kinase inhibitors. The decision for transplantation depends on a variety of clinical and biological situations. The Leukemia Net recommendations as well the NCCN guidelines help us to choose the best moment to perform ASCT. In 1998, Gratwohl and colleagues published a score in order to establish the risk of ASCT before the procedure. In 2005, the Brazilian group, studying more than 1000 patients in an independent population, validated the risk score previously proposed by the EBMT Group. In this paper we discuss the position of ASCT in a country such as Brazil that presents resource limitations. In 2006, the EBMT published an activity survey about ASCT in CML and discussed the changes in treatment indications over the past 15 years and presented differences in medical conduct in West versus East Europe concerning ASCT indication. Despite of risks, ASCT remains a valid curative treatment. To delay or to perform the ASCT in advanced phases (accelerated- or blastic-phase) increases procedure-related mortality rates and reduces the probability of cure.O transplante alogênico de célula-tronco hematopoética permanece como a única terapêutica com potencial terapêutico para a LMC in todas as fases da doença. Entretanto, os resultados com a utilização do mesilato de imatinibe são suficientemente impressionantes para deslocar a utilização do transplante para segunda ou mesmo terceira linha de tratamento dependendo da disponibilidade dos novos inibidores de tirosino quinases. A decisão para a indicação do transplante depende da fase clínica e dos achados biológicos. As recomendações da Leukemia Net e as diretrizes da NCCN nos auxiliam a escolher o melhor momento para a elaboração do transplante. Em 1998, Gratwohl e colaboradores publicaram um escore no sentido de estabelecer o risco do transplante antes de sua realização. Em 2005, um grupo brasileiro estudando mais de 1.000 pacientes em uma população independente validou o escore de risco proposto pelo grupo europeu. Neste manuscrito o autor discutirá a posição do transplante em países com limitações de recursos como o Brasil. Em 2006, a mesma escola européia publicou um estudo de monitoramento do transplante e discutiu as mudanças desta modalidade de tratamento nos últimos 15 anos e apresentou as diferenças no comportamento médico na Europa do oeste (mais rica) versus do leste (mais pobre) na indicação e utilização do transplante. A despeito dos riscos, o transplante permanece como uma terapêutica curativa válida. Atrasar a indicação ou realizar o procedimento em fases avançadas, como a fase acelerada ou blástica, aumenta o risco de mortalidade relacionada ao procedimento e reduz a probabilidade de cura.

Gemtuzumab Ozogamicin (Mylotarg®) targets leukemia cells expressing the CD 33 receptor by means of a monoclonal antibody conjugated to a cytotoxic agent, calicheamicin. It was approved for use in elderly patients with relapsed or refractory acute myeloid leukemia and reversible hepatotoxicity is common after administration. The first case of hepatic veno-occlusive disease was reported after Gemtuzumab Ozogamicin infusion in a patient who had been submitted to hematopoietic stem cell transplantation 8 months earlier. Three phase 2 studies with 188 patients with acute myeloid leukemia in first relapse that used Gemtuzumab Ozogamicin were analysed and the incidence of fatal hepatic veno-occlusive disease in these studies was < 1%, and prior hematopoietic stem cell transplantation was the most significant risk factor. The aim of this paper is to report a rare fatal case of hepatic veno-occlusive disease with rupture of the spleen vein and artery in a 68-year-old patient that had received Gemtuzumab Ozogamicin. To the best of our knowledge, it is the first case report of hepatic veno-occlusive disease with rupture of the spleen vein and artery related to Gemtuzumab Ozogamicin.Gentuzumab Ozogamicina (GO) (Mylotarg®) tem como alvo células leucêmicas que expressam CD33 através de um anticorpo monoclonal conjugado a um agente citotóxico, a caliqueamicina. Esta droga foi aprovada para uso em pacientes idosos com leucemia mielóide aguda (LMA) recaída ou refratária e hepatotoxicidade é comum após sua administração. Tack e colaboradores apresentaram o primeiro caso de doença hepática veno-oclusiva (DHVO) após infusão de GO em um paciente que tinha realizado transplante de medula( TMO) há 8 meses. Três estudos de fase II com 188 pacientes com LMA foram analisados e a incidência de HVOD fatal foi inferior a 1%, sendo a realização de TMO o fator de risco mais importante. O objetivo deste artigo é relatar um caso raro de DHVO fatal com ruptura de veia e artéria hepática em um paciente de 68 anos que recebeu GO. Acreditamos que este é o primeiro relato de HVOD com ruptura de vasos hepáticos relacionado ao uso de GO.

Some hemoglobin variants with abnormal oxygen affinity have been reported so far from various regions of the world. They can be classified by their oxygen affinity and 15 variants with low oxygen affinity have been reported. A number of hemoglobin mutants which show an abnormal affinity for oxygen have been reported, but only few cases of hemoglobin Kansas. All cases reported so far are from Japan or in Japanese families. In this paper we describe a Brazilian patient with cyanosis and hemoglobin Kansas diagnosed by an electrophoretical procedure.Hemoglobinas variantes com afinidade anormal ao oxigênio têm sido encontradas em várias partes do mundo. Pela sua afinidade ao oxigênio, estas hemoglobinas variantes têm sido classificadas e 15 variantes com baixa afinidade relatadas. Numerosas hemoglobinas mutantes com afinidade anormal têm também sido relatadas, mas somente poucos casos de Hemoglobina Kansas. Os casos são de pacientes procedentes do Japão, ou de famílias com descendentes japoneses. Neste relato descrevemos um paciente com manifestações de cianose que teve o seu diagnóstico confirmado através da eletroforese.

Hemovigilance is used to track and reduce the occurrence of adverse events associated with blood donations(1). Hemovigilance programs have now been in existence for about 20 years after being developed in 1993 in France. Although it has emerged as a tool to improve transfusion safety, many countries and centers are still in the development stage and have not yet established functioning hemovigilance systems with adequate notification. Hemovigilance is one of the most important activities of professionals in the field of blood transfusion. All professionals who deal with transfusions are involved in blood safety, from the blood bank director to quality managers, donor physicians, nurses, phlebotomists, laboratory technicians, transfusing physicians and hospital nurses. In transfusion medicine, quality starts with the process of attracting, recruiting and informing blood donor candidates and extends through all the transfusion chain to the transfused patient. Even with precise indication and correct administration, blood transfusion procedures have inherent biological risks related to health with the potential of transfusion incidents (TI), whether immediate or delayed. TI are defined as injuries occurring during or after blood transfusion that are related to the procedure. All professionals involved in prescribing and administrating blood products must be trained to identify and manage TI and to establish measures to prevent future incidents. Thus, the notification of immediate and delayed TI is essential to minimize risk(2). The safety of blood products from their source, the blood donor, until their use in the recipient is of the utmost importance. Today, the field of hemovigilance is very extensive covering blood components, tissues and cell preparations including donor vigilance, material vigilance and the safety of the patient. While hemovigilance is well known to those who work in the field of transfusion medicine, there are important differences between countries when it comes to the implementation of national hemovigilance programs. In Brazil, the blood-surveillance system was implemented by the National Health Service in 1999(3-5). Resolution number 57 of the Brazilian National Surveillance Agency, ANVISA, defines hemovigilance as "a set of surveillance procedures covering the cycle of blood, from the donation to the transfusion, generating information about adverse events resulting from the donation and the therapeutic use of blood and blood components". And follows: "This information is used to identify risks, improve the quality of products and processes and increase the donor and patient safety by preventing the occurrence or reoccurrence of these events"(4). Although regulations and laws are in place, there is a concern about underreporting undesired reactions to blood and blood products. This is still a common problem in Brazil, which shows reporting rates much lower than in countries such as France and the United Kingdom where the systems are consolidated(2). There is an international effort to establish common definitions and in bringing together the different national policies. These are pooled by diverse international and national associations that make a concentrated effort to standardize definitions and measures around the world(6). The paper on hemovigilance in the current issue of the Revista Brasileira de Hematologia e Hemoterapia illustrates how local attempts to evaluate information on adverse and unexpected reactions in the use of blood products may function in order to prevent the onset or recurrence of reactions(7). It shows that after initial resistance, there was a growing trend in the number of hemovigilance processes opened followed by a downward trend, a variation that is explained by statistical analysis. Human immunodeficiency viruses (HIV), Hepatitis B virus (HBV) and Hepatitis C virus (HCV) seroconversion cases in donors were tracked and associated to infection in the blood recipient. These cases are not dealt with unless there is an active hemovigilance system in place which shows the importance of this instrument in increasing transfusion safety. There are currently technologies that capture and analyze donor reaction information, focusing on donor hemovigilance, including monitoring, analyzing and investigating the risks involving donors at the time of blood donation or following the blood donation event. Some enable users to track the different reaction rates, provide baseline metrics and help analyze the trends and changes in reaction rates over time, thereby giving clues to the factors that affect reaction rates. They may facilitate the ability to hypothesize, design and analyze interventions, as well as to assess their impacts with the goal of improving donor and donation safety. In conclusion, there is a continuous need to work on hemovigilance; the laws and tools are in place, but there is still the need of establishing the correct awareness system in order to ensure that the procedures will be followed and that hemovigilance will help to prevent undesired reactions to blood transfusions.

The aim of the authors of the paper 'Relationship between splenomegaly and hematologic findings in patients with hepatosplenic schistosomiasis' published in this edition of the Revista Brasileira de Hematologia e Hemoterapia was to evaluate hematological and hemostatic abnormalities in patients with the severe form of schistosomiasis and its possible association with splenomegaly and portal hypertension(1). For this purpose a prospective study was performed of 55 compensated hepatosplenic schistosomiasis patients previously treated with praziquantel. All patients were outpatients of the Gastrointestinal Service of the Hospital das Clinicas of the Universidade Federal de Pernambuco (UFPE), Recife, Brazil, during the period 2010-2012. Thirty healthy individuals were selected as a control group. An abdominal ultrasound was performed in all patients and the Niamey protocols were used to measure the longitudinal diameter of the spleen and to classify the pattern of fibrosis. Moreover, routine liver tests were performed including albumin, aminotransferases (AST, ALT), alkaline phosphatase (ALP) and gamma glutamyl-transferase (γ-GT). A complete blood count and hemostatic tests such as prothrombin time/international normalization ratio (PT/INR), partial thromboplastin time (PTT), fibrinogen and D-dimer were carried out. The authors observed that patients showed predominance of advanced pattern fibrosis. Furthermore, the routine liver and hemostatic tests had increased values compared to the control group with the exception of the level of fibrinogen. There were also high frequencies of upper gastrointestinal bleeding in patients (34%) and thrombocytopenia (83%); 36.5% had anemia and 47% presented leukopenia. An inverse correlation was found between the longitudinal diameter of the spleen and the platelet count. The development of gastro-esophageal varices is a common complication of portal hypertension and bleeding from varices is a frequent cause of mortality and morbidity(2,3). As the platelet count is a commonly available parameter and measurement of the spleen bipolar diameter has a high reproducibility in abdominal ultrasound studies(4,5), their use might be of help in the clinical management of patients with Schistosoma mansoni infection and suspected esophageal varices in endemic areas. According to some authors(6,7), increases in the ALT and AST levels occur with liver cell damage, but in S. mansoni infections this type of injury is not commonly observed. On the other hand, the most important cause of increases in γ-GT is the chronic stimulation of the microsomal fraction of hepatocytes and the presence of cholestasis(8). According to Martins & Borges, chronic stimulation of the microsomal fraction of hepatocytes occurs only in patients with the hepatosplenic form of schistosomiasis. Some authors(8,9) proposed that changes in the biliary tree, due to fibrosis of the portal space, may be the anatomical substrate for the increases in the ALP and γ-GT levels in patients with the hepatosplenic form of schistosomiasis. In the literature, there is a tendency to explain hematologic changes related to portal hypertension as being due to hypersplenism just through observing hematological laboratory values(10,11). It is noteworthy that pancytopenia in portal hypertension due to schistosomiasis is caused by intra-splenic blood stasis related to difficult venous drainage to the liver. Symmers fibrosis in hepatosplenic schistosomiasis does not interfere in the function of these organs. Therefore, there is doubt regarding the term hypersplenism which is perhaps confused with the term storage. In the case of splenomegaly schistosomiasis, cytopenia may be caused by the increase in splenic storage and not by a mononuclear phagocytic system disorder(11,12). Apart from these considerations, there is the difficulty of explaining why the very low platelet and leukocyte counts found in patients with portal hypertension and schistosomiasis are not accompanied by clinical symptoms(11,13). On the other hand, coagulation disorders are frequently observed in patients with schistosomiasis even though the pathophysiology for this has not yet been established. In patients with advanced hepatosplenic schistosomiasis, high levels of the pro-inflammatory cytokines, interleukin-1 alpha (IL-1α) and tumor necrosis factor alpha (TNF-α) and lipopolysaccharide (LPS) have been detected in the sera(14). It is therefore assumed that a tissue factor procoagulant expressed by endothelial cells because of stimulation by these agents may participate in the activation of the extrinsic coagulation cascade(14). Accordingly, it may be possible that host immune responses to schistosome eggs participate in not only granuloma formation and tissue fibrosis, but also in the development of hemostatic abnormalities in schistosomiasis mansoni(14).

Red Blood Cell (RBC) alloimmunization remains a major complication for transfusion-dependent patients but factors governing risk for alloimmunization are little known. Antibody production is a serious complication in patients on long-term transfusion therapy; it may cause potentially life-threatening delayed hemolytic transfusion reactions (DHTRs), autoantibody formation as well as logistic problems, for example, to obtain timely and properly matched transfusion blood for patients in which new alloantibodies are detected. Even non-chronically transfused patients who become alloimmunized are 20 times more likely to form additional antibodies after one or more repeat transfusion events(1-3). This is not an ideal scenario for a patient population in which the benefit is proportional to the longevity of transfused RBCs and this may result in an extensive laboratory workup that consumes significant time and resources. In an effort to reduce alloimmunization, some programs have been designed and implemented to provide Rh and K antigen-matched RBC transfusions to patients who are in need of chronic transfusion support but some patients still become alloimmunized despite this antigen matching(4,5). In contrast to prophylactic antigen matching, some institutions argue that the data supporting a reduction in DHTRs are insufficient to offset the cost of labor and resources required to perform extended matching for polytransfused patients. Characterization of patients and clinical conditions with high alloimmunization risk could help in the selection of patients who need to be extensively matched. By identifying such risks, it may be possible to predict responders and non-responders, thereby avoiding the use of costly antigen-matched units for non-responders, and only selecting phenotyped/genotyped-matched units for responders to reduce alloimmunization-associated morbidity and mortality. Several factors are predicted to influence the reaction of the recipient's immune system to alloantigens including the dose and the immunogenicity of the antigen as well as genetic, and acquired patient-related factors and clinical conditions(6,7). It has also been shown that the number of transfusions plays an important role in RBC alloimmunization and that immune-compromised patients have a lower risk to develop red cell antibodies. However, other patient-related risks are little known. Although unexpected risk factors were found, such as solid tumors because of their chronic inflammatory state, there are few and limited studies showing that the inflammatory status of human transfusion recipients may regulate the immunogenicity of transfused RBCs(8). In this issue of the Revista Brasileira de Hematologia e Hemoterapia, there is an important retrospective case-control study on a small group of alloimmunized and nonalloimmunized patients with solid cancer, regarding the risk of RBC alloimmunization(9). The authors evaluated clinical factors related to the severity of the disease (ECOG performance scale, Karnofsky scale, presence of metastasis and body mass index) and inflammatory background (C-reactive protein) and concluded that these factors cannot be used to predict the risk of RBC alloimmunization in such patients. Although the relatively small number of patients is a limitation of the study, this paper represents an additional contribution in the field of RBC alloimmunization in patients with solid tumors. The results of the studies of Dinardo et al. do not ratify the thesis that the inflammatory status regulates the immunogenicity of transfused RBCs(9). This finding supports the concept that there are combinations of factors influencing the immune response to RBC antigens. We will have to look to future studies by this group and others to better understand the risk factors of RBC alloimmunization in cancer patients in order to provide or not antigen-matched RBC transfusions.

Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) syndrome is a very rare form of severe congenital neutropenia with approximately only 40 cases reported until now. The name of this syndrome, WHIM, describes its main features that include, but are not limited to warts, hypogammaglobulinemia, recurrent bacterial Infections and myelokathexis (retention and apoptosis of mature neutrophils in the bone marrow).(1,2) Although recently the molecular basis of this disease was better characterized, the diagnosis of this rare condition remains largely based on clinical features and bone marrow morphology; prompt recognition and initiation of treatment is crucial to avoid morbidity and mortality due to infections. Administration of granulocyte colony-stimulating factor (G-CSF) in this setting reportedly increases the number of neutrophils in circulation and leads to clinical improvement during episodes of bacterial infections.(3,4) Recently a 2-year-old girl was referred to our hematology clinic with a past history of recurrent infections (3 episodes of pneumonia and 5 episodes of urinary tract infection) and persistent low neutrophil counts ranging from 64 to 650 cells/µL since she was 10 months old. Her previous blood counts showed that her hemoglobin concentration and platelet counts were within the normal range. There were no abnormal findings on physical examination. Investigational tests showed hypogammaglobulinemia (gamma globulin at 0.29g/dL) on protein electrophoresis and the examination of the bone marrow aspirate revealed a hypercellular bone marrow with marked granulocytic hyperplasia characterized by an increased number of mature neutrophils with hypersegmented nuclei and cytoplasmic vacuolization. Neutrophils showed nuclear lobes often separated by long strands of chromatin (Figure 1). These typical bone marrow morphologic findings of myelokathexis in association with the clinical picture were consistent with the diagnosis of WHIM syndrome. Treatment with G-CSF (5 µg/kg per day subcutaneously) was initiated after confirmation of diagnosis leading to an increase in neutrophil count to 550 cells/µL after 12 days of therapy, 1300 cells/µL after one month and to 1836 cells/µL after 4 months (Figure 2). No side effects or new episodes of bacterial infection have been observed so far after five months of therapy. Figure 1 Morphological abnormalities of mature neutrophils on Leishman stained bone marrow aspirate film. Neutrophils show cytoplasmic vacuolization, nuclear hypersegmentation and nuclear lobes separated by long strands of chromatin Figure 2 Neutrophil counts before and after initiation of therapy with G-CSF at 5 µg/kg per day The diagnosis of WHIM syndrome was mainly based on the patient's clinical background with recurrent infections and severe chronic neutropenia and on specific laboratorial findings including hypogammaglobulinemia and, more importantly, a bone marrow aspirate showing granulocytic hyperplasia and aberrant morphology of mature neutrophils. The granulocytic hyperplasia with specific neutrophil morphological abnormalities in the bone marrow help to distinguish myelokathexis from most other forms of severe chronic neutropenia.(5) Indeed, although verrucosis and hypogammaglobulinemia are not observed in all cases, neutropenia and a hypercellular bone marrow are typically observed. In this condition, myeloid and lymphoid cells are normally generated in bone marrow but are not released to the bloodstream resulting in a hypercellular bone marrow with hypersegmented and hypermature neutrophils showing cytoplasmic vacuolization and separated nuclear lobes connected by long strands of chromatin.(6) In 2003, Hernandez et al.(7) reported that this syndrome is caused by a gain in function of a mutation in the CXC chemokine receptor 4 (CXCR4) causing partial truncation of this receptor. Expression of the truncated form of CXCR4 confers increased responsiveness of mature cells to the chemokine and prevents their marginalization to the bone marrow and subsequent release to the bloodstream. This would explain the paradoxical granulocytic hyperplasia with myelokathexis observed in our and other reports of WHIM syndrome, in which neutrophils are retained in the marrow beyond the normal time for release into circulation; they progress to apoptosis after the normal lifespan, but within the marrow rather than in the circulation and peripheral tissues. In another important paper, Aprikyan et al.(4) studied apoptotic features in four patients with myelokathexis by electron microscopy and flow cytometry, including the expression of bcl-x on granulocyte precursor subpopulations. The authors demonstrated that the insufficient supply of neutrophils to the peripheral blood in myelokathexis is caused, at least in part, by accelerated spontaneous apoptosis of bone marrow progenitor cells. They also showed that these abnormalities, including low bcl-x expression, were partially corrected by the administration of G-CSF, providing evidence of a possible drug mediated protection against apoptotic cell death. The satisfactory response to G-CSF therapy in our patient, represented by increased neutrophil counts and decreased infectious episodes, is in accordance with previous reports. In fact, G-CSF has been the standard initial therapy for all forms of severe congenital neutropenia because of the high rate of absolute neutrophil count responsiveness (= 90%) and reduced number and severity of life threatening infections prolonging survival.(8) Stem cell transplantation can be indicated for patients who are refractory to G-CSF or who develop genetic or cytogenetic abnormalities of bone marrow cells that are associated with increased risk of conversion to myelodysplastic syndrome or acute myeloid leukemia. In summary, WHIM syndrome is a very rare disease in which careful morphological examination of bone marrow aspirate is determinant for diagnosis of myelokathexis, especially in clinical settings where genetic and molecular characterization is unavailable. Prompt diagnosis allows the initiation of G-CSF therapy, which seems to diminish the frequency and intensity of infections.

A low iron level, the commonest nutritional deficiency in the world, is a public health problem in developing countries. On the other hand, an excessive amount of iron is toxic, causing several organic dysfunctions, such as diabetes, cirrhosis, endocrinopathies and heart disease. Researchers have reported an association of iron overload with beta-thalassemia. The aim of this paper was to compare the serum ferritin levels of women with the beta-thalassemia trait. The results of serologic tests of 137 women of childbearing age were analyzed; 63 had the beta-thalassemia trait and 74 had Hb AA. In the beta-thalassemia carriers, the median ferritin value was 51.90 ng/mL and in the non-carriers 31.60 ng/mL (p = 0.0052). Levels of less than 20 and above 150 ng/mL were observed in 28% and 3% of the non-carriers and in 16% and 11% of the carriers, respectively. With these results it is possible to conclude that women in the reproductive age with the beta-thalassemia trait present higher ferritin levels in the northeastern region of São Paulo State. Further studies are necessary to clarify possible genetic and/or environment factors which interfere in iron absorption.

The long history of animal experimentation describes the use of a series of methods that not only include the use of whole animals but isolated organs, isolated tissues, tissue cultures, isolated cells, subcellular components, modeling and structure-activity relationships. Data from government reports, from medical research council reports and from scientific publications point to the extent to which these methods are used. A study of the revolution of therapeutics and of the recent decline in drug innovation, raises the question as to whether the trend away from experimentation on the whole organism may have gone too far(1). Several factors were very important in the discovery of essential nutrients including the recognition that certain diseases are directly associated to diet. Subsequently, the development of suitable animal models investigated animals that have specific requirements for the nutrient in question, the use of bioassay procedures to first produce and then ameliorate one or more of the symptoms related to deficiency and the development of defined purified diets that could be made singly deficient in a nutritional entity. Generally, the diet-disease association preceded both isolation of the nutrient per se as well as the establishment of nutrient function(2,3). The STZ-diabetes model is widely used to investigate diabetic peripheral neuropathies by transmission electron microscopy (TEM). Morphological alterations of the vestibulocochlear nerve in experimental diabetes are being described for the first time and such information corroborates to a better understanding of the changes in hearing observed in diabetic patients(4). The nutritional status of animals can change these results, as can the cellular composition and emerging inflammatory reactions. Leukocyte counts can easily be studied by TEM and with the advancing age of mice the results may be different. There are several forms of causing undernourishment in animals with the most common being protein malnutrition caused by the ingestion of small quantities of milk protein - casein (about 8%), as described in the original article by Viana et al. published in this issue of the Revista Brasileira de Hematologia eHemoterapia(5). This scientific paper shows the importance of physical training on the physiological adaptation of leukocytes in situations of neonatal malnutrition. Currently many experiments are underway to try to reconcile animal research to effectively and ethically extrapolate the results to humans.

Hemoglobinopathies have been considered the most frequent hereditary disease in Brazilian population, constituting a Public Health problem. This paper reports on screening in workers at FIOCRUZ-RJ., exposed to some hazards factors such as, chemical substances, radiation, excessive cold and heat etc., with the objective of evaluating the impact of these factors in carriers of hemoglobinopathies, mainly in sickle cell trait (AS).

This paper is an analysis of the study by Yotsuyanagi et al. about the association of hepatitis B and other viruses in the etiology of non-B and non-C hepatocellular carcinomas. The authors tested for hepatitis B, hepatitis C and transfusion transmitted virus in patients suffering from hepatocellular carcinomas in Japan. Although many of these patients were negative in respect to anti- HBs and / or anti- HBc, using PCR it was possible to prove many individuals exhibited DNA of hepatitis B virus in the blood serum. The most significantly findings were in patients negative for both anti- HBs and anti- HBc. Using RT-PCR the presence of RNA of hepatitis B virus was found in the hepatic tissue in all cases, whether neoplastic or not, except in one patient.

This paper is an analysis of the study by Yotsuyanagi et al. about the association of hepatitis B and other viruses in the etiology of non-B and non-C hepatocellular carcinomas. The authors tested for hepatitis B, hepatitis C and transfusion transmitted virus in patients suffering from hepatocellular carcinomas in Japan. Although many of these patients were negative in respect to anti- HBs and / or anti- HBc, using PCR it was possible to prove many individuals exhibited DNA of hepatitis B virus in the blood serum. The most significantly findings were in patients negative for both anti- HBs and anti- HBc. Using RT-PCR the presence of RNA of hepatitis B virus was found in the hepatic tissue in all cases, whether neoplastic or not, except in one patient.