ABSTRACT
SUMMARY OBJECTIVE: Aplastic anemia (AA) is an immune-mediated disease that destroys hematopoietic cells through activated T lymphocytes. B lymphocyte-mediated humoral immunity also plays an important role in the pathogenesis of AA. Regulatory B cell (Breg) subpopulation, which is defined as "B10", secretes interleukin 10 (IL-10). The objective of our experiment was to investigate whether the scale-down proportion of B10 cells in AA patients may play a key role in the pathogenesis. METHODS: A total of 38 AA patients (14 SAA patients and 24 NSAA patients) and 20 healthy control subjects were included. All subjects did not suffer from autoimmune diseases or any other diseases affecting the immune system, such as infectious diseases. Bone marrow mononuclear cells (PBMCs) were isolated and analyzed by Flow cytometry (FCM) and Immunofluorescence double-labeling assay. The relationship between the relative proportions of B10 and ProB10 and their associations to AA, as well as disease severity, were assessed by common clinical indicators and then examined. RESULTS: Our analyses revealed AA patients had significantly lower proportions of peripheral B10 and B10pro compared to healthy controls. SAA patients had a substantially lower percentage of B10 cells and B10pro cells compared to NSAA patients. In addition, B10 cells and B10pro cells were negatively correlated with absolute neutrophil counts, hemoglobin levels and platelet, and absolute reticulocyte counts in AA patients. CONCLUSIONS: The present study attempted to elucidate the potential role of the scale-down proportion of B10 cells in the pathogenesis of AA.
RESUMO OBJETIVO: A anemia aplástica (AA) é uma doença imunomediada que destrói células hematopoiéticas por meio dos linfócitos T ativados. A imunidade humoral mediada por linfócitos B também desempenha um papel importante na patogênese da AA. A subpopulação de células B reguladoras (Breg), que é definida como "B10", secreta interleucina 10 (IL-10). No experimento, investigou-se se a proporção reduzida de células B10 nos pacientes de AA pode desempenhar um papel-chave na patogênese. MÉTODOS: Um total de 38 pacientes de AA (14 pacientes de anemia aplástica grave e 24 pacientes de anemia aplástica não grave) e 20 indivíduos de controle saudáveis foram incluídos. Todos os indivíduos não sofriam de doenças autoimunes ou de quaisquer outras doenças que afetam o sistema imunológico, tais como doenças contagiosas. As células mononucleares da medula óssea (PBMCs) eram isoladas e analisadas por citometria de fluxo (FCM) e ensaio de dupla marcação por imunofluorescência. A relação entre as proporções relativas de células B10 e as células ProB10 e as suas associações à AA, assim como a gravidade da doença avaliada por indicadores clínicos comuns, foram examinadas. RESULTADOS: Nossas análises revelaram que os pacientes de AA têm proporções significativamente menores de células B10 e células ProB10 periféricas em comparação com indivíduos de controle saudáveis. Os pacientes de anemia aplástica grave tiveram uma percentagem substancialmente menor de células B10 e células B10pro em comparação com pacientes de anemia aplástica não grave. Além disso, as células B10 e B10pro foram negativamente correlacionadas com contagens absolutas de neutrófilos, níveis de hemoglobina e plaquetas e contagem de reticulócitos absolutos nos pacientes de AA. CONCLUSÕES: Além disso, o estudo presente tentou elucidar o papel imunorregulatório potencial das células B10 na patogênese da AA e fornecer uma nova estratégia para a aplicação de imunoterapia baseada na célula B para tratar a AA no futuro.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Aged , Young Adult , B-Lymphocytes, Regulatory/pathology , Anemia, Aplastic/pathology , Reference Values , Severity of Illness Index , Bone Marrow Cells/cytology , Case-Control Studies , Cells, Cultured , Fluorescent Antibody Technique , Interleukin-10/analysis , Interleukin-10/metabolism , Reticulocyte Count , Antigens, CD19/analysis , Antigens, CD19/metabolism , Flow Cytometry , Anemia, Aplastic/blood , Leukocyte Count , Middle Aged , NeutrophilsABSTRACT
La aplasia medular es una enfermedad poco frecuente en pediatría, siendo el tratamiento de elección en las formas severas el trasplante de células progenitoras hematopoyéticas (TCPH). Gracias a los avances en TCPH, los nuevos tratamientos inmunosupresores y al adecuado tratamiento de sostén, se ha logrado en las últimas décadas una franca disminución de la mortalidad asociada a esta patología. Es por ello que uno de los principales desafíos consiste en prevenir la aparición de infecciones asociadas a la neutropenia severa y prolongada que padecen estos pacientes, siendo actualmente las infecciones bacterianas y fúngicas una de las principales causas de morbimortalidad. Por otra parte, la mayoría de las guías de manejo y tratamiento de sostén se basan en recomendaciones de expertos, siendo la evidencia escasa, más aún en pediatría. Gran parte de las recomendaciones de tratamiento empírico se basan en guías de neutropenia febril de pacientes hemato-oncológicos. A su vez, existe gran variabilidad, de acuerdo al centro de atención, en cuanto al uso de antimicrobianos para profilaxis primaria, debiéndose tener en cuenta la mayor propensión a presentar infecciones invasivas por hongos filamentosos y, en el caso de pacientes con linfopenia marcada, de enfermedad por P jirovecii a la hora de valorar la indicación de profilaxis de estos pacientes.Se detallarán a continuación las principales recomendaciones sobre manejo de prevención de infecciones y tratamiento precoz de pacientes pediátricos con aplasia medular severa.
Aplastic anemia (AA) is a rare condition in children. Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for severe idiopatic AA. Survival in severe AA has markedly improved in the past decades due to advances in HSCT, immunosuppressive and biologic drugs, as well as supportive care. Since bacterial and fungal infections are one of the principal causes of morbidity and mortality in AA, one of the main challenges is to prevent the appearance of infections associated with severe and prolonged neutropenia. Most guidelines of treatment and prophylaxis are based on expert recommendations. Given the lack of controlled studies in children with AA, most recommendations of empiric treatment rely on guidelines for febrile-neutropenia management in hemato-oncologycal patients. A great variability exists in the use of antimicrobials for primary prophylaxis among different institutions. Due to the fact that patients with severe and prolonged AA present high incidence of filamentous fungal infections, an adecuate antifungal prophylaxis is recommended. In the case of severe lymphopenia, prophylaxis against P jirovecii should also be considered. Recommendations in prophylaxis and early treatment of infections in severe pediatric AA are detailed
Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Child , Infection Control , Hematopoietic Stem Cell Transplantation , Early Diagnosis , Disease Prevention , Invasive Fungal Infections/therapy , Anemia, Aplastic/pathology , Anemia, Aplastic/prevention & controlABSTRACT
To determine the usefulness of bone marrow aspiration and trephine biopsy in evaluation of the bone marrow in routine haematological practice. This study included 443 cases of bone marrow examination, referred to Pathology Department, Lady Reading Hospital Peshawar during the period extending from January 2012 till July 2013. All the bone marrow smears and bone biopsy sections were examined in detail. The diagnosis and findings on aspirate and biopsy were evaluated and compared with each other. In 73.8% of the cases the bone marrow aspiration and trephine biopsy showed same diagnosis i.e., bone marrow aspiration alone was sufficient for diagnosis in these cases. In the remaining 116 [26.2%] cases trephine biopsy sections or touch imprints were found to be necessary in for making final diagnosis. These cases were those of the hypoplastic / aplastic marrows, Myelofibrosis, lymphomatous infiltration and chronic granulomatous inflammation. The study results suggest that both the aspirate and trephine biopsy complement each other. Nutritional anaemias, Haematological Malignanciesand Immune Thrombocytopenia can be readily diagnosed by bone marrow aspiration alone. Trephine biopsy is necessary for diagnosing Granulomatous Inflammation and Hypoplastic/Aplastic Anaemia. Also trephinebiopsy is required to diagnose Myelofibrosis and Lymphomatous infiltration
Subject(s)
Humans , Biopsy, Needle , Biopsy/methods , Diagnostic Techniques and Procedures , Bone Marrow/pathology , Anemia, Aplastic/pathology , Anemia, Megaloblastic/pathology , Hematologic Diseases/diagnosis , Myelodysplastic Syndromes/pathologyABSTRACT
Aunque rara vez se encuentra durante el embarazo, la anemia aplásica (AA) es una complicación grave que aumenta el riesgo de infección y hemorragia, aumentando la morbi-mortalidad materna; por tal motivo, se propone reportar un caso clínico de AA y embarazo. Caso Clínico: Se reporta el caso de una adolescente de 16 años, primigesta, con gestación intrauterina de 15 semanas por biometría fetal y diagnóstico de AA desde hace tres meses, tratada con ciclosporina A y prednisona; la cual ingresa por pancitopenia y cifras tensionales elevadas; conllevando a la decisión de interrumpir el embarazo debido al progresivo deterioro de la salud materna. Conclusión: Si bien la anemia en una de las principales complicaciones durante la gestación, la asociación de AA y embarazo es infrecuente(AU)
Although rarely the aplastic anemia (AA) is present during pregnancy, this is a serious complication that increases the risk of infection and hemorrhage, increased maternal morbidity and mortality; for this reason, we proposed to report a clinical case of AA and pregnancy. Case Report: To report a case of a 16-year-old adolescent, primigravida, with intrauterine gestation of 15 weeks by fetal biometry and diagnosis of AA for three months ago, treated with cyclosporine A and prednisone which is admits by pancytopenia and elevated blood pressure, leading to the decision to interrupt the pregnancy because of the progressive deterioration of maternal health. Conclusion: Although anemia in one of the major complications during pregnancy, the association of AA and pregnancy is uncommon(AU)
Subject(s)
Humans , Female , Adolescent , Pancytopenia , Pregnancy , Cyclosporine/therapeutic use , Anemia, Aplastic/pathology , Gastroenterology , Hemorrhage , InfectionsABSTRACT
A 16-yr-old male patient with hemochromatosis due to multiple packed red blood cell transfusions was referred to our emergency center for the treatment of severe aplastic anemia and dyspnea. He was diagnosed with aplastic anemia at 11-yr of age. He had received continuous transfusions because an HLA-matched marrow donor was unavailable. Following a continuous, approximately 5-yr transfusion, he was noted to develop hemochromatosis. He had a dilated cardiomyopathy and required diuretics and digitalis, multiple endocrine and liver dysfunction, generalized bleeding, and skin pigmentation. A total volume of red blood cell transfusion before deferoxamine therapy was about 96,000 mL. He received a regular iron chelation therapy (continuous intravenous infusion of deferoxamine, 50 mg/kg/day for 5 days q 3-4 weeks) for approximately seven years after the onset of multiple organ failures. His cytopenia and organ dysfunctions began to be gradually recovered since about 2002, following a 4-yr deferoxamine treatment. He showed completely normal ranges of peripheral blood cell counts, heart size, and liver function two years ago. He has not received any transfusions for the last four years. This finding suggests that a continuous deferoxamine infusion may play a role in the immune regulation in addition to iron chelation effect.
Subject(s)
Adolescent , Humans , Male , Anemia, Aplastic/pathology , Chelation Therapy/methods , Deferoxamine/therapeutic use , Erythrocyte Transfusion , Hemochromatosis/complications , Immune System , Iron/therapeutic use , Iron Chelating Agents/therapeutic use , Radiography, Thoracic/methods , Time Factors , Treatment OutcomeABSTRACT
Se presenta el caso de una paciente mujer de 31 años, con diagnóstico de anemia aplásica, quién refería disminución de agudeza visual central en el ojo derecho. Al examen del segmento anterior no había signos de sangrado. A la fundoscopía se encontraron hemorragias retinales en mancha en distinto cuadrante en cada ojo; hemorragia macular que comprometía la fovea en el ojo derecho y hemorragia preretinal con nivel en el cuadrante temporal inferior en el ojo izquierdo. Su evolución fue desfavorable, a la semana, presentó gran compromiso del sensorio, malestar general y al examen oftalmológico se encontraron hematomas subconjuntivales en ambos ojos como signo evolutivo de la severa plaquetopenia.(Rev Med Hered 2007;18:45-48).
Subject(s)
Humans , Female , Adult , Anemia, Aplastic/diagnosis , Anemia, Aplastic/etiology , Anemia, Aplastic/pathology , Anemia, Aplastic/therapy , Hemorrhage/diagnosis , Hemorrhage/therapyABSTRACT
Aplastic anemia is a group of hematologic disorders characterized by peripheral blood pancytopenia and a bypocellular bone marrow. Hematopoietic stem cells are decreased and the residual cells are often functionally defective. A preponderance of evidence suggests that acquired aplastic anemia is inmunologically mediated: activated T-lymphocytes produce increased quantities of gamma interferon and tumor necrosis factor wich result un suppression of hematopoiesis. Choice of initial treatment for apatient with aplastic anemia depends upon a complex interaction between patient age, disease severity and the availability of a bone marrow dono. Patients with mild disease may be treated with observation, androgens, colony stimulating factors or inmunossupression or bone marrow trnasplantation are indicated. As our knowledge of the pathogenesis of aplastic anemia improves, more effective, less taxic treatment should become available.
Subject(s)
Anemia, Aplastic/pathology , Anemia, Aplastic/therapyABSTRACT
La anemia de Fanconi es un desorden cromosómico caracterizado por una anemia aplástica familiar de carácter autosómico recesivo, que se manifiesta clínicamente con lesiones de piel, anormalidades congénitas de tipo esquelético, genitourinario y neuroocular, de baja prevalencia mundial. Se presenta un caso de anemia de Fanconi diagnósticado en un preescolar masculino de 33 meses de edad, hospitalizado en el Servicio de Pediatría del Hospital General "Patrocinio Peñuela Ruíz" de San Cristóbal. Se analizan los hallazgos clínicos y aspectos diagnósticos y terapéuticos de esta enfermedad
Subject(s)
Humans , Male , Child, Preschool , Blood Chemical Analysis/methods , Anemia, Aplastic/pathology , Child, Preschool , Fanconi Anemia/diagnosis , Fanconi Anemia/genetics , Fanconi Anemia/therapy , Skin/injuriesABSTRACT
OBJECTIVES: To quantitate apoptosis and Fas antigen expression of T lymphocytes by activation in aplastic anemia (AA) and compare with that of normal controls and completely-recovered AA, and to investigate the apoptotic sensitivity to anti-fas antibody of activated T lymphocytes in AA. METHODS: We studied the expression of Fas antigen on fresh T lymphocytes of twenty patients with AA [13 newly diagnosed, 7 recorvered AA after immunosuppressive therapy (IST)], and investigated the activation-induced cell death (AICD) and Fas expression by activation [interleukin-2 (200 U/ml) and phytohemagglutinin (50 micrograms/ml)] in 5 newly-diagnosed AA, 5 normal controls and 5 AA in complete response (CR). Apoptotic sensitivity to anti-Fas antibody was assessed by the time-course kinetics of induction of cell death by anti-Fas antibody (500 ng/ml). RESULTS: There was no significant difference of Fas antigen expression on freshly-isolated T lymphocytes among newly-diagnosed severe AA, normal control s and patients with AA in CR after IST. In normal controls, T lymphocytes death was greatly increased at 3 days of activation, and Fas antigen expression on T lymphocytes was increased above baseline at day 1 of activation. In contrast, in newly-diagnosed AA, T lymphocytes showed delayed cell death, which correlated with a slowed increase of Fas antigen expression by activation. Also, anti-Fa s antibody sensitivity of activated T lymphocytes was decreased in newly-diagnosed AA. In completely recovered AA, these abnormal AICD and Fas antigen expressions by activation were recovered to normal range. CONCLUSIONS: Abnormal AICD plays a role in the immune pathophysiology of AA, and defective Fas system is involved in this process.
Subject(s)
Humans , Anemia, Aplastic/pathology , Anemia, Aplastic/immunology , fas Receptor/blood , Apoptosis , Case-Control Studies , In Vitro Techniques , Lymphocyte Activation , T-Lymphocytes/pathology , T-Lymphocytes/immunology , Time FactorsABSTRACT
Se han señalado con frecuencia las causas últimas de muerte en la anemia aplástica, aunque las complicaciones en el sistema nervioso central como causa última de muerte no han sido adecuadamente estimadas en nuestro medio. Para estimar las incidencias de las mismas, se analizaron los protocolos de autopsia del Hospital México, comprendidos en un período de quince años. Alteraciones macro y microscópicas comprometiendo SNC se encontraron en un 81 porciento de los casos fatales, siendo la hemorragia subaracnoidea el hallazgo más frecuente (77 porciento), seguido de la hemorragia cerebral intraparenquimatosa (59 porciento). Se destaca además el hecho de mortalidad más precoz en hombres que en mujeres (entre los 10 y los 40 años contra 40 a 70 años respectivamente) Se insiste en la importancia del sangrado en el SNC como evento fatal final.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Anemia , Anemia, Aplastic/physiopathology , Anemia, Aplastic/pathology , Central Nervous System , Hemorrhage , Costa RicaABSTRACT
Diez pacientes con diagnóstico de aplasia medular adquirida (AM) recibieron globulina antilinfocitaria (GAL) como tratamiento. Dos pacientes eran niños de dos yocho años de edad y el resto eran adultos con una media de 32 años (rango 16-56). El intervalo medio desde el diagnóstico hasta el inicio del tratamiento fue de 5,38 meses (rango 1-20. Cinco pacientes tenían antecedentes de contacto con benceno, organofosforado y piroxicam/ampicilina. Otro paciente tenía diagnóstico ce hemoglobinuria paroxística nocturna. En los cuatro restantes no se pudo determinar la etiología. Nueve pacientes habían recibido tratamiento previamente, seis con corticoides y andrógenos y res sólo con corticoides, sin respuesta. La GAL fue administrada bajo internación, en dosis de 10-20 mg/Kg/día durante cuatro días endos pacientes y en el resto durante ocho días. Entre el séptimo y el décimo día de comenzado el tratamiento, todos los pacientes desarrollaron enfermedad del suero, que fue controlada con prednisona. A los tres meses, tres pacientes tuvieron respuesta completa, y tres pacientes respuesta parcial. Cuatro pacientes no respondieron y de ellos tres fallecierom dos por sepsis y uno por hemorragia intracerebral. Nuestros resultados demuestran una respuesta completa o parcial en el 60% de los pacientes tratados con GAL, por lo que concluimos que la GAL es una opción terapéutica eficaz para el tratamiento de la AM severa o moderada en ausencia de posibilidad de transplante de médula ósea