ABSTRACT
Hemophilia is an inherited X-linked coagulopathy defined by a deficiency or abnormality in the clotting function of factor VIII (Hemophilia A) or factor IX (Hemophilia B). Prophylaxis the regular administration of therapeutic products to maintain hemostasis and prevent bleeding is the mainstream of treatment. Addressing the development and scientific evidence for administrating prophylaxis is the goal of this review. Prophylaxis is the therapeutic modality of choice for people with severe hemophilia, being considered, in principle, a lifelong treatment. It should have an early onset, ideally as a primary, or at least secondary. Even lifelong tertiary prophylaxis seems to offer benefit, although further studies are still lacking. Individualized strategies should lead to an optimization of the dilemma between better joint outcomes versus involved costs.
Subject(s)
Humans , Male , Female , Factor VIII/therapeutic use , Hemophilia B/prevention & control , Hemophilia A/prevention & controlABSTRACT
The history of hemophilia is ancient, with descriptions dated to the 2nd century AD. The first modern narratives appeared in 1800s, when total blood transfusion was the only available treatment and life expectancy was remarkably low. Advances occurred with the use of plasma and cryoprecipitate, but only the discovered of factor concentrates revolutionized the treatment. The implantation of prophylaxis allowed hemophilic patients to prevent bleeding and the development of chronic arthropathy, although with a significant burdensome with the regular infusions. In the past 20 years, this field has witnessed major improvements, including the development of gene therapy and other pharmacological approaches.
Subject(s)
Humans , History, 19th Century , History, 20th Century , History, 21st Century , Factor IX/history , Factor VIII/history , Hemophilia B/history , Hemophilia A/history , Hemophilia B/therapy , Hemophilia A/therapyABSTRACT
Introduction: Epidemiological studies on hemophilia in the Brazilian population are historically scarce. Despite the continuous effort made by the National Program of Inherited Bleeding Disorders to map this condition, little information is available, especially on the period prior to program conception. Therefore, the present study aims to assess the epidemiological, serological, and clinical characteristics of patients with hemophilia in the state of Rio Grande do Sul, Brazil. Methods: A total of 455 patients had their medical records reviewed from January 1, 2003 to December 31, 2007. Results: We observed a remarkable prevalence of hepatitis C virus (HCV) infection in patients with both hemophilia A and B, and this prevalence significantly increased along with age (p < 0.001). No positive anti-HCV results were observed among children younger than 5 years old. There was a significant correlation between the severity of hemophilia and the number of arthropathies in all age categories. Considering the presence of inhibitors, a significant difference was observed between age groups, as older patients had higher inhibitor titers. There was a significant correlation between mean coagulation factor consumption and the number of arthropathies in patients over 5 years old. Conclusions: This profile analysis of patients with hemophilia reflects a gradual improvement in treatment safety and efficiency, as well as the need for continued investment in this population. (AU)
Subject(s)
Humans , Male , Female , Hepatitis C/epidemiology , Hemophilia A/epidemiology , Patients/statistics & numerical data , Cohort Studies , Hemophilia B/epidemiologyABSTRACT
ABSTRACT Objective: To assess clinical outcomes of intolerant, relapsed or refractory patients who could not be treated with new tyrosine kinase inhibitors or experimental therapies. Methods: A retrospective cohort of 90 chronic myeloid leukemia patients in all phases of the disease treated with imatinib mesylate as their first TKI therapy, and with dasatinib or nilotinib as the next line of therapy. We evaluated clinical outcomes of these patients, with special focus on the group that needed more than two therapy lines. Results: Thirty-nine percent of patients were refractory or intolerant to imatinib. An 8-year overall survival rate of the patients who went through three or more lines of treatment was significantly lower, compared to those who were able to maintain imatinib as their first-line therapy (83% and 22%, respectively p < 0.01). Decreased overall survival was associated with advanced-phase disease (p < 0.01), failure to achieve major molecular response in first-line treatment (p < 0.01) and interruption of first-line treatment due to any reason (p = 0.023). Failure in achieving complete cytogenetic response and major molecular response and treatment interruption were associated with the progression to the third-line treatment. Conclusion: The critical outcome observed in relapsed, intolerant or refractory chronic phase CML patients reflects the unmet need for this group of patients without an alternative therapy, such as new drugs or experimental therapies in clinical trials. Broader access to newer treatment possibilities is a crucial asset to improve survival among CML patients, especially those refractory or intolerant to first-line therapies.
Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Survival Analysis , Imatinib Mesylate , DasatinibABSTRACT
BACKGROUND: The development of nutrition care programs for patients undergoing hematopoietic stem cell transplantation is necessity in view of the rapid and aggressive consequences frequently seen with this procedure. Patients require constant care to reduce complications and to contribute to the success of therapy. METHODS: In an attempt to ascertain the impact of systematic nutritional care on patients submitted to allogeneic hematopoietic stem cell transplantation, the present study assessed the nutritional and clinical status, use of parenteral nutrition, and complication and mortality rates in two groups of patients, who were submitted to transplantation between April 2003 and December 2004 (Non-intervention Group - NIG; n = 57) and between March 2006 and January 2008 (Intervention Group - IG; n = 34). RESULTS: There were no significant differences between groups in terms of clinical or nutritional profiles. Additionally, the length of hospital stay and complication and mortality rates were similar for both groups. However, time on parenteral nutrition during treatment was shorter for the IG [median 6.5 days (range: 1-28) for related donor recipients and 11 days (range: 1-21) for unrelated donor recipients] than for the NIG [median 20.5 days (range, 4-73) for patients submitted to myeloablative conditioning and 18.5 days (range: 11-59 days) for those submitted to nonablative conditioning]. CONCLUSION: The implementation of a nutritional follow-up and therapy protocol for adult patients submitted to hematopoietic stem cell transplantation shortens the duration of parenteral nutrition. It certainly has an impact on hospitalization costs and, potentially, on the rate of complications, even though this was not demonstrated in this study.
Subject(s)
Humans , Nutrition Assessment , Bone Marrow Transplantation , Nutritional Support , Stem Cell Transplantation , Parenteral Nutrition SolutionsABSTRACT
BACKGROUND: The expression of CD56 is considered a bad prognostic factor for overall survival, lower rates or short complete remission and extramedullary invasion but the results are controversial. The importance of validating new prognostic parameters in acute leukemias was the reason to investigate the CD56 expression in blast cells of patients with acute myeloid leukemia. METHODS: A cohort of 48 patients treated at Hospital de Clinicas de Porto Alegre and diagnosed with acute myeloid leukemia as classified by the French-American-British group (FAB) criteria using cell morphology, cytochemistry and flow cytometry were evaluated. RESULTS: Eight cases (16.7 percent) were CD56 positive without correlation to age or gender. The highest incidence of CD56 positivity was in FAB subtypes M4 and M5. The death rate during induction was not significantly different between patients with and without CD56 expression (62.5 percent vs. 27.5 percent; p-value = 0.097). However, patients that expressed CD56 had significantly lower overall survival than those who did not (mean 4.0 months vs. 14.5 months; p-value = 0.03). CONCLUSIONS: The data suggest that expression of CD56 in acute myeloid leukemia may be indicative of poor prognosis because it is associated with a shorter overall survival. The death rate during induction was not significantly different despite an apparent difference in proportions between groups.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , PrognosisABSTRACT
O objetivo deste trabalho foi definir diretrizes para a indicação do transplante de células-tronco hematopoéticas (TCTH) no tratamento da leucemia mieloide aguda (LMA) no Brasil. O papel do TCTH no tratamento da LMA foi discutido pelosautores e apresentado para a Sociedade Brasileira de Transplante de Medula Óssea na reunião sobre Diretrizes Brasileiras para o TCTH, que o ratificou. Este consenso foi baseado na revisão da literatura internacional e na experiência brasileira em TCTH para o tratamento da LMA. O tratamento ideal para leucemia mieloide aguda em primeira remissão completa (1RC) ainda não está definido. Há consenso na indicação do TCTH alogênico, com condicionamento mieloablativo, para pacientes que apresentem alterações citogenéticas consideradas de alto risco. O TCTH alogênico não está indicado na 1RC para pacientes de baixo risco citogenético e, aparentemente, o TCTH alogênico, autólogo ou a quimioterapia de consolidação são equivalentes para os pacientes de risco intermediário.
The objective of this work was to define guidelines for the indication of hematopoietic stem cells transplantation (HSCT) in the treatment of acute myeloid leukemia (AML) in Brazil. The role of HSCT in the treatment of AML was discussed by the authors and presented to the Brazilian Society of Bone Marrow Transplantation in a meeting to formulate and ratify the Brazilian Guidelines on HSCT. This consensus was based on a review of international publications and on the Brazilian experience in HSCT for the treatment of AML. The optimal treatment for AML in first complete remission (1CR) has not been defined yet. There is consensus on the indication of allogeneic HSCT with myeloablative conditioning for patients who present high risk cytogenetic changes. Allogeneic HSCT is not indicated for low cytogenetic risk 1RC patients and, apparently, allogeneic and autologous HSCT and consolidation chemotherapy are similar for intermediate risk patients.
Subject(s)
Humans , Bone Marrow , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, AcuteABSTRACT
Introdução: O transplante de células-tronco hematopoiéticas (TCTH) alogênico é um procedimento que oferece um potencial de cura para doenças hematológicas malignas e benignas. O benefício da técnica está especialmente relacionado ao aumento da sobrevida em pacientes com doadores HLA-compatíveis em cujos casos o tratamento quimioterápico mostrou-se insuficiente ou ineficaz. Objetivos: Analisar a sobrevida de pacientes que receberam TCTH alogênico aparentado no Serviço de Hematologia Clínica e Transplante de Medula Óssea (SHCTMO) do Hospital de Clínicas de Porto Alegre (HCPA). Métodos: Estudo de coorte prospectiva com análise de sobrevida de pacientes transplantados entre 1994 e 2003. Resultados: Foram analisados 133 pacientes com idade média de 30,8±14,8 anos com um tempo médio de 26,8 meses entre o diagnóstico e o TCTH. Cinco anos após o transplante, 71 pacientes (53,4%) estavam vivos, 22 pacientes tinham leucemia mieloide aguda (LMA), 54, leucemia mieloide crônica (LMC), e seis padeciam de síndrome mielodisplásica (SMD), sendo que, em 5 anos, a sobrevida foi de 52, 50 e 33%, respectivamente. Dos 26 pacientes transplantados por anemia aplásica (AA), 66,7% tinham idade inferior a 20 anos, e 61,5% dos que tinham mais de 20 anos estavam vivos. Conclusão: Embora, no nosso estudo, o tempo médio entre o diagnóstico e o transplante tenha sido superior a 2 anos, e embora nossa análise tenha sido apenas estratificada pelo tipo da doença, independentemente do regime de condicionamento ou da fase da doença no momento do TCTH, nossos resultados são superponíveis aos descritos na literatura mundial.
Background: Hematopoietic stem cell transplantation (HSCT) represents a curative alternative for malignant and benign hematological diseases. The benefits of the technique are especially related to an increase in the survival of patients with HLA-compatible hematopoietic stem cell donors when chemotherapy or clinical therapy has resulted ineffective. Objectives: To analyze the survival of patients submitted to allogeneic HSCT at the Hematology and Bone Marrow Transplant Service of Hospital de Clínicas de Porto Alegre. Methods: A prospective cohort of all patients submitted to transplantation between 1994 and 2003 was analyzed for overall survival. Results: A total of 133 patients were submitted to transplantation in the study period, with a mean age of 30.8±14.8 years; mean time elapsed between diagnosis and transplant was 26.8 months. Five years after the procedure, 71 patients (53.4%) were alive, 22 patients had acute and 54 had chronic myeloid leukemia, and six patients presented myelodysplastic syndrome; the 5 year overall survival was 52, 50, and 33%, respectively. Of the 26 patients transplanted for aplastic anemia, 66.7% had 20 or less years of age, and 61.5% of the patients older than 20 years were alive. Conclusion: Although the mean time elapsed between diagnosis and transplantation was over 2 years and although our results were stratified by type of disease only, the findings herein reported are similar to those found in the literature, independently of conditioning regimen or disease stage at the time of transplant.
Subject(s)
Humans , Male , Female , Survival Rate/trends , Bone Marrow Transplantation/adverse effects , Bone Marrow Transplantation/methods , Bone Marrow Transplantation/mortality , Bone Marrow Transplantation/pathology , Bone Marrow Transplantation/psychology , Hematologic Diseases/diagnosis , Hematologic Diseases/epidemiology , Hematologic Diseases/mortality , Hematologic Diseases/prevention & control , Hematologic Diseases/psychology , Hematologic Diseases/therapy , Stem Cell TransplantationABSTRACT
A hemostasia requer um interessante equilíbrio entre a coagulação e a fibrinólise. Durante a formação de um trombo, os polímeros as fibrina são degradados pela plasmina e passam a dar origem a produtos de degradação de diferentes pesos moleculares. O menor e melhor caracterizado destes produtos é o D-dímero. Embora baixos níveis de D-dímero possam ser detectados na circulação de indivíduos saudáveis, seus níveis aumentam significativamente nos pacientes com trombose venosa profunda (TVP), embolia pulmonar (EP), coagulação intravascular disseminada, infarto do miocárdio, câncer, sepse, entre outros. O D-dímero é reconhecido atualmente como o mais específico indicador de ativação da coagulação e de fibrinólise. Os ensaios para a detecção de D-dímero são utilizados em muitos laboratórios na investigação de distúrbios hemostáticos associados com a ativação do sistema fibrirnolítico, incluindo os eventos tromboembólicos. A sua principal aplicação clínica diz respeito à possibilidade de exclusão diagnóstica de distúrbios tromboembólicos quando os seus níveis estão normais.
Subject(s)
Blood Coagulation , Disseminated Intravascular Coagulation , Fibrinolysis , Pulmonary Embolism , Thromboembolism , Venous Thrombosis , Enzyme-Linked Immunosorbent Assay , Myocardial Infarction/diagnosis , Neoplasms , SepsisABSTRACT
A alta prevalência de beta-talassemia em italianos e a participação dos mesmos na formação étnica da cidade de Caxias do Sul e arredores, Rio Grande do Sul, Brasil, conduziram-nos à investigação de hemoglobinopatias em uma amostra de 608 doadores de sangue do Hemocentro Regional de Caxias do Sul. Apesar da influência étnica, encontramos 1,81 por cento de hemoglobinas anormais (0,16 por cento Hb AC, 0,99 por cento, Hb AS e 0,66 por cento Hb AH), um padrão similar com o estudo do interior do Estado do Rio Grande do Sul para alterações qualitativas. Para as talassemias, as técnicas mais comuns, cruzadas com seqüenciamento de DNA, em nossas mãos, não foram capazes de esclarecer anormalidades quantitativas da hemoglobina. Esse resultado pode ser atribuído a alterações genéticas ainda não conhecidas, a limitações técnicas ou, mais simplesmente, à miscigenação.
Subject(s)
Blood Donors , Hemoglobinopathies , Electrophoresis , Genetic TestingABSTRACT
This study was conducted to establish the frequency of hemoglobinopathies among newborns undergoing screening tests for metabolic diseases at the University Hospital (Hospital de ClÝnicas) in Porto Alegre, Rio Grande do Sul, Brazil. Testing for abnormal hemoglobins was performed by isoelectric focusing electrophoresis on agarose gel with blood obtained by heel stick and applied to filter paper. For confirmatory testing of abnormal neonatal screening, a venopuncture blood sample was obtained from the infant and parents and then submitted to hemoglobin electrophoresis on cellulose acetate at pH 8.6 and citrate agar at pH 6.2. A total of 1,615 subjects were studied: 20 samples showed the Hb S pattern and six samples showed Hb C. Thus, frequency of the sickle cell gene was 1.2 and that of the Hb C gene was 0.4, regardless of race or origin. These data suggest that the inclusion of universal neonatal screening for hemoglobinopathies in the ongoing projects for the detection of phenylketonuria and congenital hypothyroidism has many advantages and should be considered in health programs.
Subject(s)
Humans , Male , Female , Infant, Newborn , Anemia, Sickle Cell , Hemoglobin C Disease/epidemiology , Neonatal Screening , Anemia, Sickle Cell , Birth Weight , Brazil , Chi-Square Distribution , Hemoglobin C Disease/diagnosis , Isoelectric Focusing , Pilot Projects , PrevalenceABSTRACT
A transfusäo de sangué é reconhecida como o segundo mais importante modo de transmissäo da doença de Chagas. Este estudo faz um levantamento dos métodos empregados em diversos bancos de sangue para detectar doadores infectados e prevenir esta iatrogenia e compara as áreas controladas por órgäos oficiais com aquelas de maior prevalência da doença
Subject(s)
Humans , History, 20th Century , Chagas Disease/transmission , Blood Transfusion/adverse effects , Brazil , PrevalenceABSTRACT
A transfusäo de sangue é reconhecida como o segundo mais importante modo de transmissäo da Doença de Chagas. Este estudo faz um levantamento dos métodos empregados em diversos Bancos de Sangue para detectar doadores infectados e prevenir esta iatrogenia e compara as áreas controladas por órgäos oficiais com aquelas de maior prevalência da Doençça