RESUMO
Despite adequate immunization and penicillin prophylaxis, bacterial infections remain a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). Besides hyposplenism, inflammatory and genetic factors might modulate their susceptibility to bacterial infections. We performed a candidate gene association of single nucleotide polymorphisms (SNPs) located in Toll-like receptor (TLR) genes, encoding prominent molecules for innate immune responses, with the occurrence of bacterial infections in patients with SCD. A cohort followed in centres in Brazil, France and Senegal (n = 430) was divided in two groups: patients who presented at least one episode of bacterial infection (n = 235) and patients who never had bacterial infections (n = 195). There were no differences in gender or age distribution among the groups. The frequency of the TLR2 rs4696480 TA genotype was significantly lower in the infected group (50% vs. 67%, odds ratio [OR] = 0·50, 95% confidence interval [CI] 0·34-0·75, P < 0·001), and the TT genotype was significantly higher in the infected group (15% vs. 5%, OR = 3·18, 95% CI 1·53-6·61, P < 0·001). Previous reports demonstrated higher secretion of inflammatory factors in cells from AA individuals, lower occurrence and severity of immune diseases in T carriers. The rs4696480 TA genotype might stand between deleterious effects of over inflammatory response (AA genotype) and inefficient responses (TT genotype) to infectious agents in SCD settings.
Assuntos
Anemia Falciforme/genética , Anemia Falciforme/microbiologia , Infecções Bacterianas/genética , Receptor 2 Toll-Like/genética , Adolescente , Adulto , África/epidemiologia , Idoso , Anemia Falciforme/epidemiologia , Anemia Falciforme/imunologia , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/imunologia , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemAssuntos
Hemólise/imunologia , Monócitos/citologia , Reticulócitos/citologia , Adulto , Células Cultivadas , Centrifugação , Humanos , MasculinoRESUMO
BACKGROUND: The complexity of Rh genetic variation among sickle cell disease (SCD) patients is high. Conventional molecular assays cannot identify all genetic variants already described for the RH locus as well as foresee novel alleles. Sequencing RHD and RHCE is indicated to broaden the search for Rh genetic variants. AIMS: To standardize the Next Generation Sequencing (NGS) strategy to assertively identify Rh genetic variants among SCD patients with serologic suspicion of Rh variants and evaluate if it can improve the transfusion support. METHODS: Thirty-five SCD patients with unexplained Rh antibodies were enrolled. A NGS-based strategy was developed to genotype RHD and RHCE using gene-specific primers. Genotype and serological data were compared. RESULTS: Data obtained from the NGS-based assay were gene-specific. Ten and 25 variant RHD and RHCE alleles were identified, respectively. Among all cases of unexplained Rh antibodies, 62% had been inaccurately classified by serological analysis and, of these, 73.1% were considered as relevant, as were associated with increased risk of hemolytic reactions and shortage of units suitable for transfusion. CONCLUSION: The NGS assay designed to genotype RH coding regions was effective and accurate in identifying variants. The proposed strategy clarified the Rh phenotype of most patients, improving transfusion support.
Assuntos
Anemia Falciforme/diagnóstico , Anemia Falciforme/genética , Variação Genética , Genótipo , Sistema do Grupo Sanguíneo Rh-Hr/genética , Alelos , Anemia Falciforme/sangue , Anemia Falciforme/terapia , Transfusão de Sangue/métodos , Gerenciamento Clínico , Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Isoanticorpos/sangue , Isoanticorpos/imunologia , Fenótipo , Reprodutibilidade dos TestesRESUMO
Anemia é comum em idosos e é associada a significante morbidade e mortalidade. Mais de 10 por cento dos indivíduos acima de 65 anos tem anemia. Com uma proporção crescente da população mundial atingindo idade igual ou superior a 65 anos, a prevalência de anemia certamente aumentará no futuro. O diagnóstico precoce é importante para prevenir piora do quadro, diminuir progressão da doença e melhorar a evolução dos pacientes. Os critérios mais utilizados em estudos epidemiológicos para definir anemia em idosos são os da OMS (hemoglobina<12 g/dL para mulheres e hemoglobina <13 g/dL para homens). Aproximadamente um terço dos idosos com anemia tem deficiência de ferro, folato e/ou vitamina B12, um terço tem insuficiência renal e/ou inflamação crônica e o terço remanescente tem anemia inexplicada. A anemia ferropênica é microcítica e hipocrômica e caracteriza-se por baixos níveis de ferritina sérica, capacidade total de ligação de ferro do plasma aumentada, saturação da transferrina diminuída, concentração do receptor solúvel da transferrina elevada e ausência de ferro na medula óssea. É causada geralmente por perda de sangue pelo trato gastrointestinal devido a gastrite, úlceras, câncer de colo ou angiodisplasia. Anormalidades do trato gastrointestinal podem ser identificadas na maioria dos pacientes. Em alguns casos, ingestão ou absorção inadequada de ferro pode contribuir para a anemia. Entretanto, em todos os casos deveria ser exaustivamente investigada e excluída perda de sangue antes de assumir que a deficiência de ferro é devida a outras causas. O tratamento inclui parar o sangramento e repor o ferro.
Anemia is a common problem in the elderly and is associated with significant morbidity and mortality. More than 10 percent of all individuals above the age of 65 have anemia. Because an increasing proportion of the world's population is aged 65 and older, it is inevitable that the prevalence of anemia will increase in the future. Thus, early diagnosis of anemia is important to prevent the condition from worsening, to slow disease progression, and improve outcomes in patients. The WHO definition of anemia (hemoglobin concentration <12 g/dL, in women and <13 g/dL, in men) is most often used in epidemiologic studies of older adults. Among older adults with anemia approximately one-third have evidence of iron, folate, and/or vitamin B12 deficiency, another third have renal insufficiency and/or chronic inflammation, and the remaining third have anemia that is unexplained. Anemia due to iron deficiency (IDA) is microcytic and hypochromic. Low serum ferritin levels, high total iron-binding capacity, low transferrin saturation, high concentrations of soluble transferrin receptor, and absent bone marrow iron stores accompany IDA. Iron deficiency in the elderly usually occurs as a result of chronic gastrointestinal blood loss caused by gastritis, ulcers, colon cancer, or angiodysplasia. Gastrointestinal tract abnormalities can be identified in the majority of patients with IDA. In some cases, inadequate intake or inadequate absorption of iron may contribute to the anemia. However, in all cases blood loss should be investigated and excluded before assuming that iron deficiency is due to other causes. Treatment includes stopping blood loss and replacing iron.
Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Idoso , Anemia/prevenção & controleRESUMO
O pulmão é um dos principais alvos de complicações agudas e crônicas nas doenças falciformes (DF). A síndrome torácica aguda é a segunda causa de internação hospitalar apresentando considerável morbimortalidade. O suporte clínico de alta qualidade é a base do tratamento bem sucedido. A administração adequada de fluidos, a analgesia, a oxigenioterapia, a fisioterapia respiratória ativa e o uso criterioso de transfusões sanguíneas são elementos essenciais do tratamento. A hipertensão pulmonar (HP), por sua vez, tem sido recentemente reconhecida como uma das complicações mais graves e freqüentes destes pacientes. A pressão de artéria pulmonar deve ser medida periodicamente por meio de ecocardiografia. Se o diagnóstico de HP for confirmado, o uso de hidroxiuréia, anticoagulação, transfusões e oxigênio deveriam ser considerados. As manifestações cardíacas nas DF incluem cardiomegalia, isquemia miocárdica, disfunção ventricular e cor pulmonale. O tratamento destas complicações deve seguir as recomendações das diretrizes atuais.
The lung is a major target organ for acute and chronic complications in sickle cell disease. Acute chest syndrome is the second most common cause of hospital admission resulting in considerable morbidity and mortality. The mainstay of successful treatment remains high quality supportive care. Fluid management, analgesia, oxygenation, bronchodilators, incentive spirometry and judicious use of transfusion therapy are essential elements of supportive care management. Pulmonary hypertension (PHT) has emerged as one of the most frequent and serious complications in these patients. The pulmonary artery pressure should be evaluated periodically by echocardiography. If the PHT diagnosis is positive the use of hydroxiurea, anticoagulation, transfusions and oxygen therapy should be considered. Cardiac manifestations are common including enlargement of the heart, myocardial ischaemia, ventricular dysfunction and cor pulmonale. The management of these complications follows the current guidelines.
Assuntos
Humanos , Anemia Falciforme , Doença da Hemoglobina SC , Hipertensão Pulmonar , Síndrome Coronariana Aguda/complicaçõesRESUMO
OBJECTIVE: To study the effects of recombinant human erythropoietin (rHuEpo) in preterm newborns (PTNs) with serious infectious diseases. METHODS: A not randomized case-control study was carried out in 34 preterm newborns with diagnosis of serious infectious pathologies, gestational age up to 35 weeks, birth weight less than 1500 g and clinical stability. Newborns selected for treatment with rHuEpo received 400 U/kg erythropoietin ss, subcutaneously twice a week. Oral iron supplementation was initiated when the levels of serum ferritin were lower than 60 mcg/l. The study was continued for six weeks or until the patient was discharged from the hospital. Erythropoiesis, granulopoiesis, thrombocytopoiesis, the need for transfusions and the occurrence of new episodes of infectious disease were analyzed. RESULTS: In the treated group there was a significant increase in the number of reticulocytes, although there was no statistically significant difference between the groups with regard to the number or volume of transfusions. There was no significant difference in neutrophils and platelet values. CONCLUSION: The use of rHuEpo, 800 U/kg/week, in PTNs with infectious diseases was effective in inducing erythropoiesis, without significant changes in the number of neutrophils or platelets. This strategy, and the accurate control of the blood collected for laboratory exams, may be beneficial for prevention of the anemia in PTNs with serious infectious diseases.