Comparative transcriptomic analysis of circulating endothelial cells in sickle cell stroke.

Ischemic stroke (IS) is one of the most impairing complications of sickle cell anemia (SCA), responsible for 20% of mortality in patients. Rheological alterations, adhesive properties of sickle reticulocytes, leukocyte adhesion, inflammation and endothelial dysfunction are related to the vasculopathy observed prior to ischemic events. The role of the vascular endothelium in this complex cascade of mechanisms is emphasized, as well as in the process of ischemia-induced repair and neovascularization. The aim of the present study was to perform a comparative transcriptomic analysis of endothelial colony-forming cells (ECFCs) from SCA patients with and without IS. Next, to gain further insights of the biological relevance of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction network (PPI) construction and in silico prediction of regulatory factors were performed. Among the 2469 DEGs, genes related to cell proliferation (AKT1, E2F1, CDCA5, EGFL7), migration (AKT1, HRAS), angiogenesis (AKT1, EGFL7) and defense response pathways (HRAS, IRF3, TGFB1), important endothelial cell molecular mechanisms in post ischemia repair were identified. Despite the severity of IS in SCA, widely accepted molecular targets are still lacking, especially related to stroke outcome. The comparative analysis of the gene expression profile of ECFCs from IS patients versus controls seems to indicate that there is a persistent angiogenic process even after a long time this complication has occurred. Thus, this is an original study which may lead to new insights into the molecular basis of SCA stroke and contribute to a better understanding of the role of endothelial cells in stroke recovery.

Current and emerging gene therapies for haemophilia A and B.

INTRODUCTION: After decades of stumbling clinical development, the first gene therapies for haemophilia A and B have been commercialized and have normalized factor (F)VIII and factor (F)IX levels in some individuals in the long term. Several other clinical programs testing adeno-associated viral (AAV) vector gene therapy are at various stages of clinical testing. DISCUSSION: Multiyear follow-up in phase 1/2 and 3 studies showed long-term and sometimes curative but widely variable and unpredictable efficacy. Liver toxicities, mostly low-grade, occur in the 1st year in at least some individuals in all haemophilia A and B trials and are poorly understood. Wide variability and unpredictability of outcome and slow decline of FVIII levels are a major disadvantage because immune responses to AAV vectors preclude repeat dosing, which otherwise could improve suboptimal or restore declining expression, while overexpression may predispose to thrombosis. Long-term safety outcomes will need lifelong monitoring because AAV vectors infused at high doses integrate into chromosomes at rates that raise questions about potential oncogenicity and necessitate vigilance. Alternative gene transfer systems employing gene editing and/or non-viral vectors are under development and promise to overcome some limitations of the current state of the art for both haemophilia A and B. CONCLUSIONS: AAV gene therapies for haemophilia have now become new treatment options but not universal cures. AAV is a powerful but imperfect gene transfer platform. Biobetter FVIII transgenes may help solve some problems plaguing gene therapy for haemophilia A. Addressing variability and unpredictability of efficacy, and delivery of gene therapy to ineligible patient subgroups may require different gene transfer systems, most of which are not ready for clinical translation yet but bring innovations needed to overcome the current limitations of gene therapy.

Promoting pain coping skills in haemophilia: A remote intervention integrating exercise and pain education.

BACKGROUND: Chronic joint pain is a significant and widespread symptom in people with haemophilia (PWH). Despite medical advancements, effective pain management remains challenging. AIM: This study presents an innovative approach that integrates remote physical exercises, pain neuroscience education, and coping strategies to address chronic pain in PWH. METHODS: The remote intervention consisted of sixteen 5-min videos encompassing physical exercises for chronic pain management and pain education strategies. These videos formed an 8-week remote intervention program. Clinical and physical assessments were conducted before and after the intervention. RESULTS: A total of thirty-one PWHs, with a median age of 34 years (ranging from 16 to 59 years), completed the remote intervention. The study revealed significant improvements in pain intensity, disability, and physical performance among PWH with chronic pain. Enhanced functional capacity was evident in the Timed Up and Go and Single Leg Stance tests, accompanied by improved scores on the Functional Independence Score in Haemophilia (FISH). Although lacking a control group, our findings are consistent with other successful exercise and pain education programs. CONCLUSIONS: This innovative intervention holds promise for managing chronic pain in PWH, underscoring patient empowerment, education, and collaboration. Notably, our study stands out by uniquely combining pain education and coping strategies, bolstering evidence for effective pain management.

The effectiveness and safety of octocog alfa in patients with hemophilia A: up to 7-year follow-up of the real-world AHEAD international study.

Background: Real-world data assessing treatment outcomes in patients with hemophilia A in routine clinical practice are limited. Objective: To evaluate the effectiveness and safety of octocog alfa in patients with moderate/severe hemophilia A receiving treatment in clinical practice. Design: The international Antihemophilic Factor Hemophilia A Outcome Database study is an observational, noninterventional, prospective, multicenter study. Methods: This planned interim data read-out was conducted following 7 years of observation of patients receiving octocog alfa (cut-off, 30 June 2020). The primary endpoint was joint health status, assessed by the Gilbert Score. Secondary endpoints included annualized bleeding rates (ABRs), Hemophilia Joint Health Score (HJHS), health-related quality of life, consumption, and safety. This post hoc analysis stratified data by hemophilia severity at baseline [moderate, factor VIII (FVIII) 1-5%; severe, FVIII <1%]. Results: Of the 711 patients in this analysis, 582 (82%) were receiving prophylaxis with octocog alfa at enrollment, and 498 (70%) had severe disease. Median Gilbert Scores were higher with on-demand therapy versus prophylaxis and scores were comparable in moderate and severe disease. In patients receiving prophylaxis, there was an improvement in HJHS Global Gait Score over 7 years of follow-up overall and in patients with severe disease. ABRs and annualized joint bleeding rates were low across all 7 years. An ABR of zero was reported in 34-56% of prophylaxis patients versus 20-40% in the on-demand group. ABRs were similar in severe and moderate disease. In total, 13/702 (1.9%) patients experienced 18 treatment-related adverse events. Conclusion: These data demonstrate the long-term effectiveness and safety of octocog alfa in patients with moderate and severe hemophilia A, especially in those receiving prophylaxis. The high number of patients receiving on-demand treatment experiencing zero bleeds could be due to selection bias within the study, with patients with less severe disease more likely to be receiving on-demand treatment. Trial registration: ClinicalTrials.gov: NCT02078427.

Comparative Effectiveness of Valoctocogene Roxaparvovec and Prophylactic Factor VIII Replacement in Severe Hemophilia A.

INTRODUCTION: A prospective, non-interventional study (270-902) followed 294 adults with severe hemophilia A (SHA) receiving prophylactic factor VIII (FVIII). From these participants, 112 rolled over into a single-arm, multicenter, phase 3 trial (GENEr8-1; NCT03370913) that evaluated efficacy and safety of valoctocogene roxaparvovec, a gene therapy that provides endogenous FVIII in individuals with SHA. Participants from 270-902 who did not roll over provide an opportunity for a contemporaneous external control. Therefore, the comparative effectiveness of valoctocogene roxaparvovec vs FVIII prophylaxis was evaluated using propensity scoring (PS). METHODS: This post hoc analysis compared 112 participants from GENEr8-1 (treated cohort) to 73 participants in 270-902 who did not enroll in GENEr8-1 (control cohort). The primary analysis used standardized mortality ratio weighting to re-weight baseline characteristics of the control cohort to better match the treated cohort. Mean annualized bleeding rates (ABR) for treated and all bleeds were compared between cohorts along with the proportion of participants with zero bleeds (treated and all bleeds). Sensitivity and scenario analyses were also conducted. RESULTS: PS adjustments reduced differences in baseline characteristics between cohorts. Mean treated (4.40 vs 0.85; P < 0.001) and all (5.01 vs 1.54; P < 0.001) ABR were significantly lower, and the proportions of participants with zero treated bleeds (82.1% vs 32.9%; P < 0.001) and all bleeds (58.0% vs 28.5%; P < 0.001) were significantly higher in GENEr8-1. CONCLUSIONS: PS-adjusted analyses were consistent with prior intra-individual comparisons. Compared with participants receiving prophylactic FVIII, the participants receiving valoctocogene roxaparvovec experienced lower ABR, and a higher proportion had zero bleeds. TRAIL REGISTRATION: ClinicalTrials.gov identifier, NCT03370913.

Hemophilia A is a bleeding disorder where blood is unable to clot properly because of a missing protein called factor VIII (FVIII). Individuals with hemophilia A have an increased risk of prolonged bleeding episodes that can be deadly. To prevent bleeding, people with severe hemophilia A need to routinely inject treatment into the skin or vein (prophylaxis). While effective, some people find the time and effort needed to maintain frequent injections difficult, since some forms of the prophylaxis must be administered in a hospital setting. Valoctocogene roxaparvovec is a gene therapy where a single injection provides instructions to the liver of individuals with hemophilia A to make the missing protein (FVIII). Then, their own liver cells can produce FVIII protein and prevent bleeding episodes. The valoctocogene roxaparvovec clinical trial compared the number of treated bleeding episodes participants had prior to gene therapy, while using prophylaxis, with the number of treated bleeding episodes after gene therapy. On average, after gene therapy, participants had 4.1 fewer treated bleeding episodes per year. In this study, mathematical models were used to explore how differences in participant's physical characteristics, such as body weight or medical history, might influence the effectiveness of gene therapy. Even when considering differences in the participants' physical characteristics, the gene therapy reduced treated bleeding episodes by 3.6 events per year. This study confirms results originally presented from the valoctocogene roxaparvovec clinical trial and reinforces confidence in the ability of valoctocogene roxaparvovec to reduce bleeding outcomes for participants with hemophilia A.

Cost of hemophilia A in Brazil: a microcosting study.

BACKGROUND: Patients with Hemophilia are continually monitored at treatment centers to avoid and control bleeding episodes. This study estimated the direct and indirect costs per patient with hemophilia A in Brazil and evaluated the cost variability across different age groups. METHODS: A prospective observational research was conducted with retrospective data collection of patients assisted at three referral blood centers in Brazil. Time-driven Activity-based Costing method was used to analyze direct costs, while indirect costs were estimated based on interviews with family and caregivers. Cost per patient was analyzed according to age categories, stratified into 3 groups (0-11;12-18 or older than 19 years old). The non-parametric Mann-Whitney test was used to confirm the differences in costs across groups. RESULTS: Data from 140 hemophilia A patients were analyzed; 53 were 0-11 years, 29 were 12-18 years, and the remaining were older than 19 years. The median cost per patient per year was R$450,831 (IQR R$219,842; R$785,149; $174,566), being possible to confirm age as a cost driver: older patients had higher costs than younger's (p = 0.001; median cost: 0-11 yrs R$299,320; 12-18 yrs R$521,936; ≥19 yrs R$718,969). CONCLUSION: This study is innovative in providing cost information for hemophilia A using a microcosting technique. The variation in costs across patient age groups can sustain more accurate health policies driven to increase access to cutting-edge technologies and reduce the burden of the disease.

The translational gap for gene therapies in low- and middle-income countries.

Gene therapies are designed to address the root cause of disease. As scientific understanding of disease prevention, diagnosis, and treatment improves in tandem with technological innovation, gene therapies have the potential to become safe and effective treatment options for a wide range of genetic and nongenetic diseases. However, as the medical scope of gene therapies expands, consideration must be given to those who will benefit and what proactive steps must be taken to widen development and access potential, particularly in regions carrying a high disease burden.

Three-year outcomes of valoctocogene roxaparvovec gene therapy for hemophilia A.

BACKGROUND: Valoctocogene roxaparvovec transfers a human factor (F)VIII coding sequence into hepatocytes of people with severe hemophilia A to provide bleeding protection. OBJECTIVES: To present 3-year efficacy and safety in the multicenter, open-label, single-arm, phase 3 GENEr8-1 trial. METHODS: GENEr8-1 enrolled 134 adult males with severe hemophilia A who were receiving FVIII prophylaxis. Efficacy endpoints included annualized bleeding rate, annualized FVIII utilization, FVIII activity (chromogenic substrate assay; imputed as 1 IU/dL at baseline and 0 IU/dL after discontinuation), and the Haemophilia-Specific Quality of Life Questionnaire for Adults. Safety was assessed by adverse events (AEs). RESULTS: At week 156, 131 of 134 participants remained in the study; overall, 17 of 134 resumed prophylaxis. Mean annualized bleeding rate for treated bleeds decreased from 4.8 (SD, 6.5) bleeds/y at baseline to 0.8 (SD, 2.3; P < .0001) bleeds/y after prophylaxis (prophylaxis cessation to last follow-up) and 0.97 (SD, 3.48) bleeds/y during year 3. Annualized FVIII utilization decreased 96.8% from baseline after prophylaxis and 94.2% during year 3. At week 156, mean and median FVIII activity were 18.4 (SD, 30.8) and 8.3 IU/dL, respectively. FVIII activity decrease was lower between years 2 and 3 than between years 1 and 2. At the end of year 3, clinically meaningful improvements in the Haemophilia-Specific Quality of Life Questionnaire for Adults Total Score were observed (mean change from baseline, 6.6; 95% CI, 4.24-8.87; P < .0001). Mild alanine aminotransferase elevations remained the most common AE during year 3 (23.7% of participants). A serious AE of B-cell acute lymphoblastic leukemia was considered unrelated to treatment. CONCLUSION: Hemostatic efficacy was maintained, and safety remained unchanged from previous years.

The molecular mechanism responsible for HbSC retinopathy may depend on the action of the angiogenesis-related genes ROBO1 and SLC38A5.

HbSC disease, a less severe form of sickle cell disease, affects the retina more frequently and patients have higher rates of proliferative retinopathy that can progress to vision loss. This study aimed to identify differences in the expression of endothelial cell-derived molecules associated with the pathophysiology of proliferative sickle cell retinopathy (PSCR). RNAseq was used to compare the gene expression profile of circulating endothelial colony-forming cells from patients with SC hemoglobinopathy and proliferative retinopathy (n = 5), versus SC patients without retinopathy (n = 3). Real-time polymerase chain reaction (qRT-PCR) was used to validate the RNAseq results. A total of 134 differentially expressed genes (DEGs) were found. DEGs were mainly associated with vasodilatation, type I interferon signaling, innate immunity and angiogenesis. Among the DEGs identified, we highlight the most up-regulated genes ROBO1 (log2FoldChange = 4.32, FDR = 1.35E-11) and SLC38A5 (log2FoldChange = 3.36 FDR = 1.59E-07). ROBO1, an axon-guided receptor, promotes endothelial cell migration and contributes to the development of retinal angiogenesis and pathological ocular neovascularization. Endothelial SLC38A5, an amino acid (AA) transporter, regulates developmental and pathological retinal angiogenesis by controlling the uptake of AA nutrient, which may serve as metabolic fuel for the proliferation of endothelial cells (ECs) and consequent promotion of angiogenesis. Our data provide an important step towards elucidating the molecular pathophysiology of PSCR that may explain the differences in ocular manifestations between individuals with hemoglobinopathies and afford insights for new alternative strategies to inhibit pathological angiogenesis.

EFFECTIVENESS OF VISCOSUPPLEMENTATION IN THE TREATMENT OF HEMOPHILIC ARTHROPATHY: A SYSTEMATIC REVIEW.

Objective: To describe the efficacy of using viscosupplementation in patients with hemophilic arthropathy (HA), on pain, limb functionality, and quality of life. Methods: A systematic review of the literature was performed following the PRISMA guidelines without limitations of language or year of publication. The search was performed on the following medical databases: PubMed, Cochrane Library, EMBASE, BVS/BIREME, Scopus, Web of Science, EBSCOhost, and PROQUEST in April 2020. The search used the following word: (hemophilia AND joint diseases) OR (haemophilic arthropathy OR hemophilic arthropathy) AND viscosupplementation. Results: The systematic review identified 127 articles, 10 of which were selected for data extraction and qualitative analysis. The 10 selected articles included 297 joints with HA in 177 hemophilic subjects. Our review showed positive results in alleviating pain and improving functional capacity, and quality of life. No major adverse effects were observed. Conclusion: There is a lack of scientific evidence regarding viscosupplementation with hyaluronic acid, but the results presented in this research suggest that it is an effective and safe therapeutic option to alleviate pain and improve functional capacity in patients with HA. Level of Evidence II, Systematic Review.

Objetivo: Descrever o uso da viscossuplementação com ácido hialurônico em pacientes com artropatia hemofílica (HA), sua eficácia na dor, a funcionalidade do membro e a qualidade de vida após sua aplicação. Métodos: Revisão sistemática da literatura (RSL) que seguiu as diretrizes PRISMA, sem limitação de idioma ou ano de publicação. A pesquisa foi realizada em abril de 2020 nas seguintes bases de dados médicas: PubMed, Cochrane Library, EMBASE, BVS/BIREME, Scopus, Web of Science, EBSCOhost e ProQuest. A estratégia de pesquisa foi: (hemofilia AND joint disease) OR (artropatia hemofílica OU artropatia hemofílica) E viscossuplementação. Resultados: A RSL identificou 127 artigos, dos quais 10 foram selecionados para extração de dados e análise qualitativa. Os 10 artigos selecionados incluíram 297 articulações com AH em 177 indivíduos hemofílicos. Nossa revisão mostrou resultados positivos na melhora da dor, na capacidade funcional e na qualidade de vida. Não foram observados efeitos adversos importantes. Conclusão: A evidência científica atual a respeito da viscossuplementação com ácido hialurônico é escassa, mas os resultados apresentados nesta pesquisa sugerem que é uma opção terapêutica eficaz e segura para diminuir a dor e melhorar a capacidade funcional em pacientes com AH. Nível de Evidência II, Revisão Sistemática.

Extended half-life recombinant factor VIII treatment of hemophilia A in Brazil: an expert consensus statement

Introduction Treatment of hemophilia A in Brazil is offered to all patients at no cost. However, several unmet medical needs exist. Method In this study, we applied the Delphi method to discuss with seven hemophilia A specialists the challenges that patients and the health system face regarding hemophilia A treatment and opportunities for improvement. Results A consensus was obtained regarding the number of weekly infusions and patient adherence to treatment. The bleeding profile, unfavourable pharmacokinetics (PKs), low adherence and high daily activity were patient profiles that would benefit from using the extended half-life (EHL) recombinant factor VIII (rFVIII). The advantages of treatment with the EHL rFVIII were the lower number of infusions per week, which could increase patient adherence and decrease the risk of bleeds, due to a more constant plasma level, a lower value. Additionally, the EHL rFVIII could improve quality of life, especially in patients with high daily activity, such as adolescents and young adults. The panelists mentioned that EHL rFVIII, if available, could be offered first to the priority group (adolescents between 12 and 19 years old), followed by adults (20 to 64 years old) and elderly people (over 65 years old). Conclusion In summary, the EHL rFVIII offers the optimal prophylaxis by decreasing the dose frequency, increasing the treatment adherence and improving the QoL, without compromising safety and efficacy.

Effectiveness of viscosupplementation in the treatment of hemophilic arthropathy: a systematic review / Efetividade da viscossuplementação no tratamento da artropatia hemofílica: uma revisão sistemática

ABSTRACT Objective: To describe the efficacy of using viscosupplementation in patients with hemophilic arthropathy (HA), on pain, limb functionality, and quality of life. Methods: A systematic review of the literature was performed following the PRISMA guidelines without limitations of language or year of publication. The search was performed on the following medical databases: PubMed, Cochrane Library, EMBASE, BVS/BIREME, Scopus, Web of Science, EBSCOhost, and PROQUEST in April 2020. The search used the following word: (hemophilia AND joint diseases) OR (haemophilic arthropathy OR hemophilic arthropathy) AND viscosupplementation. Results: The systematic review identified 127 articles, 10 of which were selected for data extraction and qualitative analysis. The 10 selected articles included 297 joints with HA in 177 hemophilic subjects. Our review showed positive results in alleviating pain and improving functional capacity, and quality of life. No major adverse effects were observed. Conclusion: There is a lack of scientific evidence regarding viscosupplementation with hyaluronic acid, but the results presented in this research suggest that it is an effective and safe therapeutic option to alleviate pain and improve functional capacity in patients with HA. Level of Evidence II, Systematic Review.

RESUMO Objetivo: Descrever o uso da viscossuplementação com ácido hialurônico em pacientes com artropatia hemofílica (HA), sua eficácia na dor, a funcionalidade do membro e a qualidade de vida após sua aplicação. Métodos: Revisão sistemática da literatura (RSL) que seguiu as diretrizes PRISMA, sem limitação de idioma ou ano de publicação. A pesquisa foi realizada em abril de 2020 nas seguintes bases de dados médicas: PubMed, Cochrane Library, EMBASE, BVS/BIREME, Scopus, Web of Science, EBSCOhost e ProQuest. A estratégia de pesquisa foi: (hemofilia AND joint disease) OR (artropatia hemofílica OU artropatia hemofílica) E viscossuplementação. Resultados: A RSL identificou 127 artigos, dos quais 10 foram selecionados para extração de dados e análise qualitativa. Os 10 artigos selecionados incluíram 297 articulações com AH em 177 indivíduos hemofílicos. Nossa revisão mostrou resultados positivos na melhora da dor, na capacidade funcional e na qualidade de vida. Não foram observados efeitos adversos importantes. Conclusão: A evidência científica atual a respeito da viscossuplementação com ácido hialurônico é escassa, mas os resultados apresentados nesta pesquisa sugerem que é uma opção terapêutica eficaz e segura para diminuir a dor e melhorar a capacidade funcional em pacientes com AH. Nível de Evidência II, Revisão Sistemática.

Desenvolvimento de um Serious Game para crianças com hemofilia / Development of a serious game for children with hemophilia / Desarrollo de un serious game para niños con hemofilia

This work describes the development process of the interface of an educational game that is aimed at children with hemophilia. The development and evaluation process used the dynamic Braindraw, Participatory Heuristic Evaluation and Beta Test and involved the end users of the game: children with hemophilia. The hypothesis is that children learn more about the disease through the game, which motivates them in an interactive practice. The experiments performed confirmed that the children with hemophilia learned more about the disease with the game...

Este trabalho descreve o processo de desenvolvimento da interface de um jogo educativo destinado à crianças com hemofillia. O processo de desenvolvimento e avaliação foram realizados através das dinâmicas Braindraw, Avaliação Heurística Participativa e Teste Beta e envolveu os usuários finais do jogo: crianças com hemofilia. A hipótese é que a criança com hemofilia parende mais sobre a doença através de um jogo, que as motiva de foma prática e interativa. Os experimentos realizados confirmaram que as crianças com hemofilia aprenderam mais sobre a doença com o jogo...

Este artículo describe el proceso de desarrollo de un juego educativo destinado a la interfaz hemofilia niños. El proceso de desarrollo y la evaluación se realizó mediante las dinámica Braindraw, Evaluación Heurística Participativa y Pruebas Beta y los usuarios finales involucrados en el juego: los niños con hemofilia. La hipótesis es que los niños con hemofilia parende más acerca de la enfermedad a través de un juego, lo que motiva la foma práctica e interactiva. Los experimentos confirmaron que los niños con hemofilia han aprendido más acerca de la enfermedad con el juego...

Diagnosis and treatment of congenital hemophilia with inhibitors: A Latin American perspective / Diagnóstico y tratamiento de la hemofilia congénita con inhibidores: Una perspectiva latinomericana

The Committee of Latin America on the Therapeutics of Inhibitor Groups (CLOTTING) is composed of a number of hemophilia specialists from Latin America. The group aims to encourage the adoption of a good standard of care for Latin American patients with hemophilia. The occurrence of inhibitors in patients with hemophilia poses clinical challenges, and it is estimated that between 1000 and 3 000 patients in Latin America are affected by hemophilia with inhibitors. There is an urgent need to establish a regional consensus and clinical guidelines for the diagnosis and treatment of these patients. We present an extensive review based on best current clinical practice and published literature, as seen from a Latin American perspective, taking into account the variable nature of hemophilia care available in the various countries in this Region.

El Comité Latinoamericano sobre la Terapéutica de Personas con Inhibidores (CLOTTING) está compuesto por un grupo de especialistas en hemofilia de Latinoamérica. El objetivo del grupo es promover la adopción de un estándar de tratamiento óptimo para los pacientes con hemofilia en Latinoamérica. La prevalencia de inhibidores en pacientes con hemofilia en Latinoamérica determina desafíos clínicos y se estima que de 1000 a 3000 pacientes en esta región están afectados con hemofilia e inhibidores. Existe una necesidad urgente de establecer un consenso regional y guías clínicas para el diagnóstico y tratamiento de estos pacientes. Nosotros presentamos una revisión exhaustiva basada en las mejores prácticas clínicas vigentes y en los datos publicados en la literatura, con una perspectiva latinoamericana, tomando en cuenta la variabilidad existente de los tratamientos de la hemofilia disponibles en los diferentes países de esta Región.

As características da Megacariopoese nas Síndromes Mielodisplásicas / The characteristics of a megakaryocyte in myelodysplasia

As síndromes mielodisplásicas säo um grupo heterogêneo de distúrbios do precursor hemopoiético pluripotencial. Encontra-se frequentemente aumento de número e atipias nos precursores megacariocíticos. Examinamos a megacariopoese em 25 pacientes com SMD ao diagnóstico e a comparamos com a de oito doadores de medula óssea usados como controles. Os megacariócitos estiveram aumentados em 16/25 casos usando-se o anticorpo CD61 e em 12/25 casos quando se usou o CD42b. O número de megacariócitos contados em cortes de medula óssea correlacionou com o de células CD42b positivas, mas näo com o de células CD61 positivas. Houve, porém, uma correlaçäo entre os resultados das duas técnicas imunocitoquímicas. Assim, as três técnicas foram úteis para avaliar a megacariopoese nas SMD. O CD61, porém, evidenciou os precursores mais imaturos.

A importância do ácido trans-retinóico no tratamento da leucemia promielocítica aguda e suas complicaçöes / The importance of trans-retinoic acid in the acute promyelocytic leukemia treatment and its complications

Os autores apresentam uma revisao da literatura relacionada à utilizaçäo do ácido trans-retinóico na Leucemia Mielóide Aguda M3. Apresentam ainda os principais parâmetros para a sua utilizaçäo, bem como os cuidados no reconhecimento e tratamento da síndrome do Acido all-transretinóico. Os autores ilustram tal revisäo com um caso em que ocorreram as mais importantes complicaçöes com a utilizaçao do Acido all-transretinóico. Os modificadores da resposta biológica têm sido cada vez mais usados no tratamento de neoplasias, e a utilizaçäo do Acido all-transretinóico tem sido altamente significativa no tipo de LMA-M3.