Hemoglobin A2 values in sickle cell disease patients quantified by high performance liquid chromatography and the influence of alpha thalassemia

BACKGROUND: In sickle cell disease, the quantification of Hb A2 is important for the differential diagnosis between sickle cell anemia (Hb SS) and Hb S/ß0-thalassemia.OBJECTIVE: To determine Hb A2 levels as quantified by high performance liquid chromatography in patients with sickle cell anemia (Hb SS) and with the SC hemoglobinopathy, with or without concomitant alpha thalassemia.METHODS: This is a retrospective study of 242 children aged between two and six years with diagnoses of Hb SS or Hb SC. The hemoglobin was evaluated using high performance liquid chromatography and alpha thalassemia [3.7 kb deletion (-a3.7)] was detected by polymerase chain reaction. Patients were classified as homozygous (-a3.7/-a3.7), heterozygous (-a3.7/a), or homozygous wild-type. Analysis of variance was used to compare the mean Hb A2 values between the alpha thalassemia groups.RESULTS: The mean (± standard deviation) Hb A2 concentrations in the Hb SS group (n = 135) was 3.68 ± 0.65%. The mean values for individuals with Hb SS and heterozygous (n = 28) or homozygous for alpha thalassemia (n = 3) were 3.98 ± 0.64% and 4.73 ± 0.25%, respectively. The mean Hb A2 of all the Hb SC patients (n = 107) was 4.01 ± 0.507 with 4.29 ± 0.41% and 4.91 ± 0.22% in individuals heterozygous (n = 23) and homozygous for alpha thalassemia (n = 7), respectively. All patients homozygous for alpha thalassemia had Hb A2 levels above 3.5%. However, Hb A2 values above 5.2% were seen in patients with Hb SS and Hb SC, independently of alpha thalassemia.CONCLUSION: Hb A2 levels are elevated in patients with Hb S or Hb C, and are directly influenced by the alpha thalassemia genotypes.

Hemoglobin A2 values in sickle cell disease patients quantified by high performance liquid chromatography and the influence of alpha thalassemia.

BACKGROUND: In sickle cell disease, the quantification of Hb A2 is important for the differential diagnosis between sickle cell anemia (Hb SS) and Hb S/ß(0)-thalassemia. OBJECTIVE: To determine Hb A2 levels as quantified by high performance liquid chromatography in patients with sickle cell anemia (Hb SS) and with the SC hemoglobinopathy, with or without concomitant alpha thalassemia. METHODS: This is a retrospective study of 242 children aged between two and six years with diagnoses of Hb SS or Hb SC. The hemoglobin was evaluated using high performance liquid chromatography and alpha thalassemia [3.7kb deletion (-α(3.7))] was detected by polymerase chain reaction. Patients were classified as homozygous (-α(3.7)/-α(3.7)), heterozygous (-α(3.7)/α), or homozygous wild-type. Analysis of variance was used to compare the mean Hb A2 values between the alpha thalassemia groups. RESULTS: The mean (±standard deviation) Hb A2 concentrations in the Hb SS group (n=135) was 3.68±0.65%. The mean values for individuals with Hb SS and heterozygous (n=28) or homozygous for alpha thalassemia (n=3) were 3.98±0.64% and 4.73±0.25%, respectively. The mean Hb A2 of all the Hb SC patients (n=107) was 4.01±0.507 with 4.29±0.41% and 4.91±0.22% in individuals heterozygous (n=23) and homozygous for alpha thalassemia (n=7), respectively. All patients homozygous for alpha thalassemia had Hb A2 levels above 3.5%. However, Hb A2 values above 5.2% were seen in patients with Hb SS and Hb SC, independently of alpha thalassemia. CONCLUSION: Hb A2 levels are elevated in patients with Hb S or Hb C, and are directly influenced by the alpha thalassemia genotypes.

Breastfeeding and the anthropometric profile of children with sickle cell anemia receiving follow-up in a newborn screening reference service / Aleitamento materno e perfil antropométrico de crianças com doença falciforme acompanhadas em serviço de referência em triagem neonatal

OBJECTIVE: To study the breastfeeding history (BF) and the anthropometric status of children with Sickle Cell Disease (SCD). METHODS: A cross-sectional study of 357 children with SCD aged between 2 and 6 years, regularly followed at a Newborn Screening Reference Service (NSRS) between November 2007 and January 2009. The outcome was anthropometric status and the exposures were: BF pattern, type of hemoglobinopathy and child's age and gender. RESULTS: The mean (SD) age was 3.7 (1.1) years, 52.9% were boys and 53.5% had SCA (hemoglobin SS). The prevalence of exclusive breastfeeding (EBR) up to six months of age was 31.5%, the median EBR times (p25-p75) was 90.0 (24.0-180.0) days and the median weaning ages (p25-p75) was 360.0 (90.0-720.0) days respectively. Normal W/H children experienced EBR for a mean duration almost four times longer than malnourished children (p=0.01), and were weaned later (p<0.05). Height deficit was found in 5.0% of children, while all the children with severe short stature had had SCA (hemoglobin SS) and were older than 4 years of age. CONCLUSIONS: EBF time and weaning age were greater than that found in the literature, which is a possible effect of the multidisciplinary follow-up. Duration of EBF and later weaning were associated with improved anthropometric indicators.

OBJETIVO: Descrever a história de aleitamento materno (AM) e estado antropométrico de crianças com doença falciforme (DF). MÉTODOS: Estudo transversal com 357 crianças com hemoglobinopatias SS e SC de dois e seis anos, acompanhadas regularmente num Serviço de Referência em Triagem Neonatal (SRTN) entre novembro de 2007 e janeiro de 2009. O desfecho correspondeu ao estado antropométrico e as exposições foram: padrão do AM, tipo de hemoglobinopatia, faixa etária e sexo da criança. RESULTADOS: A média (DP) de idade observada foi de 3,7 (1,1) anos, 52,9% meninos e 53,5% com hemoglobinopatia SS. A prevalência de aleitamento materno exclusivo (AME) até o sexto mês foi de 31,5%, a mediana (p25-p75) do tempo de AME foi de 90 (24-180) dias e a mediana (p25-p75) da idade de desmame foi de 360 (90-720) dias. Crianças eutróficas em relação ao P/A tiveram o tempo de AME, em média, quase quatro vezes maior do que os desnutridos (p < 0,01), bem como foram desmamadas mais tarde (p < 0,05). O déficit de altura foi encontrado em 5% das crianças e todas as crianças com baixa estatura grave tinham hemoglobinopatia SS e mais de quatro anos. CONCLUSÕES: O tempo de AME e a idade de desmame foram superiores aos encontrados na literatura, possível efeito do acompanhamento multidisciplinar. A duração do AME e a idade mais tardia de desmame foram associadas a melhores indicadores antropométricos.

[Breastfeeding and the anthropometric profile of children with sickle cell anemia receiving follow-up in a newborn screening reference service]. / Aleitamento materno e perfil antropométrico de crianças com doença falciforme acompanhadas em serviço de referência em triagem neonatal.

OBJECTIVE: To study breastfeeding history (BF) and the anthropometric status of children with Sickle Cell Disease (SCD). METHODS: A cross-sectional study of 357 children with SS and SC hemoglobinopathies aged between 2 and 6 years old receiving regular follow-up at a Newborn Screening Reference Service (NSRS) between November 2007 and January 2009. The outcome was anthropometric status and the exposures were: BF pattern, type of hemoglobinopathy and child's age and sex. RESULTS: The average (SD) age was 3.7 (1.1) years, 52.9% were boys and 53.5% had SS hemoglobinopathy. The prevalence of exclusive breastfeeding (EBR) up to six months of age was 31.5%, the median EBR times (p25-p75) was 90.0 (24.0-180.0) days and the median weaning ages (p25-p75) was 360.0 (90.0-20.0) days respectively. Normal W/H children experienced EBR for an average duration almost four times longer than malnourished children (p=0.01), and were weaned later (p<0.05). Height deficit was found in 5.0% of children, while all the children with severe short stature had SS hemoglobinopathy and were over 4 years of age. CONCLUSIONS: EBR time and weaning age were greater than found in the literature, which is a possible effect of the multidisciplinary follow-up. Duration of EBR and later weaning were associated with improved anthropometric indicators.

Prevalence and molecular characterization of ß-thalassemia in the state of Bahia, Brazil: first identification of mutation HBB: c.135delC in Brazil.

ß-Thalassemia (ß-thal) is a hereditary disease with at least 200 known causative molecular defects, with a limited number of distinct mutations predominating in any given population. The Brazilian population is one of the most heterogeneous in the world. Although occurrences of ß-thal in this country have been recognized for a long time and previous studies have shown important regional differences related to the mutational profile, no extensive analysis of mutations of the HBB gene has been carried out in Brazil. We examined 1011 teenagers from Bahia, a state located in the northeast of Brazil. Hematological data were obtained using automated cell counting, hemoglobin (Hb) profiles were studied by high performance liquid chromatography (HPLC), and DNA was analyzed by automated sequencing. None of the four Mediterranean mutations that are most frequently found in South and Southeast Brazil (HBB: c.118C>T; HBB: c.93-21G>A; HBB: c.92+1G>A; HBB: c.92+6T>C), was found to be responsible for thalassemia in the cases that we studied. One heterozygote for a frameshift mutation at codon 44 (-C) was identified. This is the first study to determine the prevalence and profile of ß-thal in Bahia State. For the first time in Brazil, we report the occurrence of the HBB: c.135delC mutation in the ß-globin gene.

Programa de triagem neonatal para hemoglobinopatias em Dourados, MS: uma análise / Neonatal screening program for hemoglobinopathies in Dourados, MS: an analysis

Embora estejam bem definidos os benefícios da implantação do programa de triagem neonatal para hemoglobinopatias, não são raros os estudos que apontam falhas nesses programas. Este estudo teve como objetivo avaliar o programa de triagem neonatal para hemoglobinopatias no município de Dourados, estado do Mato Grosso do Sul (MS). Foram entrevistadas, através da aplicação de formulários, 32 famílias cujos filhos foram identificados como portadores de hemoglobinopatias, durante a triagem neonatal, no período de janeiro de 2000 a dezembro de 2005. Adicionalmente, foram verificadas a cobertura do Programa Nacional de Triagem Neonatal (PNTN) e a incidência de hemoglobinopatias no MS, de 2000 a 2005. Dos 242 casos de hemoglobinopatias diagnosticados neste período, a heterozigose para hemoglobina S demonstrou incidência de 1,37 por cento, a heterozigose para hemoglobina C, 0,37 por cento e a heterozigose para hemoglobina D, 0,007 por cento. Não foram diagnosticados casos de anemia falciforme. A cobertura encontrada foi de 81,4 por cento. Foram detectadas falhas, como a não reconvocação para o exame confirmatório, ausência de encaminhamento médico para orientação, falta de investigação familiar e a falha na compreensão do aconselhamento genético.

Although the benefits of implanting a neonatal screening program for hemoglobinopathies are well defined, there are many studies that point to failures in these programs. The objective of this study was to evaluate the efficiency of the neonatal screening program for hemoglobinopathies in the municipality of Dourados, in the state of Mato Grosso do Sul, Brazil. Between January 2000 and December 2005, thirty-two families with children diagnosed during neonatal screening as having hemoglobinopathies were evaluated using questionnaires. Additionally, the coverage of the Brazilian National Neonatal Screening Program and the incidence rates of hemoglobinopathies in the state of Mato Grosso do Sul between 2000 and 2005 were analyzed. Of the 242 cases of hemoglobinopathies that were diagnosed in this period, 1.37 percent individuals were identified as heterozygotes for hemoglobin S, 0.37 percent for hemoglobin C, and 0.07 percent for hemoglobin D. There were no cases of sickle cell anemia diagnosed during this period. The program was found to be positive and provided a broad coverage of 81.4 percent. Some failures were detected such as not requiring patients to return for confirmation examinations, the lack of medical counseling and follow through, lack of investigations of family histories, and lack of understanding on the part of the family of the genetic counseling they received.

[Sickle cell disease and infection]. / Anemia falciforme e infecções.

OBJECTIVE: To discuss the high prevalence of sickle cell disease in our environment and the increased morbidity and mortality as a result of infection associated with this condition. SOURCES OF DATA: Review of MEDLINE from 1986 to 2003. We found around 600 references about the subject. Thirty-five journal articles were reviewed, in addition to chapters in two text books. SUMMARY OF THE FINDINGS: We discuss general information concerning sickle cell disease as well as a few topics about the most frequently observed infections in these patients. Drug prophylaxis and immunizations are also covered. CONCLUSIONS: This review hopes to provide the pediatric community with information concerning the association between sickle cell disease and infections, so as to minimize the occurrence of complications.

Anemia falciforme e infecções / Sickle cell disease and infection

OBJETIVO: A alta prevalência de anemia falciforme em nosso meio e a elevada morbimortalidade por infecções associada a esta condição estimularam a realização deste artigo de revisão. FONTE DE DADOS: Realizamos uma revisão bibliográfica no banco de dados MEDLINE no período de 1986 até 2003. Foram encontradas cerca de 600 referências sobre o tema, sendo selecionados 35 artigos, os quais, aliados a capítulos de dois livros-textos, compuseram esta revisão. SíNTESE DOS DADOS: Neste artigo, além de informações gerais a respeito da doença falciforme, são abordados alguns tópicos sobre as infecções mais freqüentemente observadas no paciente com anemia falciforme, assim como a profilaxia medicamentosa e imunizações disponíveis. CONCLUSÕES: Esta é uma revisão que visa fornecer à comunidade pediátrica informações sobre o binômio anemia falciforme e infecções, a fim de minimizar suas complicações nesta comunidade específica.

Expiratory trigger setting in pressure support ventilation: from mathematical model to bedside.

OBJECTIVE: To evaluate the feasibility of relying on a mathematical model to adjust the optimal level of expiratory trigger, materialized by the ratio of inspiratory flow at the end of inspiratory effort (V'ti) and peak inspiratory flow (V'peak), or V'ti/V'peak, during pressure support, by comparing its predicted values with those measured in intubated patients. DESIGN: Prospective observational study. SETTING: Medical intensive care unit, university hospital. PATIENTS: There were 28 intubated patients undergoing pressure support. INTERVENTIONS: Pressure support as set by the clinician in charge. MEASUREMENTS AND MAIN RESULTS: A significant correlation was found between predicted and measured V'ti/V'peak ratios (r =.70; p <.001; mean +/- sd difference, -0.025 +/- 0.07; 95% confidence interval, -0.161 to 0.111). Overall, delayed cycling occurred in obstructive conditions, the delay increasing as obstructive disease was more severe. CONCLUSIONS: A significant correlation was observed between predicted values of V'ti/V'peak and those values measured in patients undergoing pressure support. These findings should stimulate further research into the possible applications of this mathematical model to optimize expiratory trigger setting. Furthermore, our findings suggest that expiratory trigger should be adjustable and provide a wider range of cutoff levels than that which is currently available.

Comparative bench study of triggering, pressurization, and cycling between the home ventilator VPAP II and three ICU ventilators.

OBJECTIVE: To compare triggering, pressurization, and cycling of the home ventilator VPAP II with those of three ICU ventilators (Evita 4, Galileo, and Servo 300). DESIGN AND SETTING: Two-compartment lung model study in a research laboratory, university hospital. METHODS: One compartment was driven by an ICU ventilator to mimic "patient" inspiratory effort, while the other was connected to the tested ventilator. Pressure support of 10, 15, 20, and 25 cmH2O, and inspiratory efforts of 5, 10, 15, 20, and 25 cmH2O (inspiratory time 1 s) were used in normal, obstructive, and restrictive conditions. Triggering delay (Td), triggering workload, pressurization at 300 and 500 ms, and difference between the "patient's" inspiratory time and that of the ventilator were analyzed. RESULTS: No difference was noted in triggering workload between VPAP II, Evita 4, and Galileo while Servo 300 had a lower value. Pressurization at 300 ms on Evita 4 and Servo 300 reached 75% of the ideal value, on Galileo 35%, and on VPAP II 45%. Pressurization at 500 ms on Evita 4 and Servo 300 reached 85% of the ideal value, on Galileo 50%, and on VPAP II 55%. Cycling was delayed in obstructive conditions and premature in restrictive conditions with each of the devices. CONCLUSIONS: The VPAP II performed as well as one ICU ventilator and less well than two. Home devices for noninvasive ventilation in acute respiratory failure outside the ICU could prove attractive as they are smaller, less costly, and easier to use than ICU machines.

Spinal cord compression in beta-thalassemia: follow-up after radiotherapy

Context: Spinal cord compression due to extramedullary hematopoiesis is a well-described but rare syndrome encountered in several clinical hematologic disorders, including beta-thalassemia. Case Report: We report the case of a patient with intermediate beta-thalassemia and crural paraparesis due to spinal cord compression by a paravertebral extramedullary mass. She was successfully treated with low-dose radiotherapy and transfusions. After splenectomy, she was regularly followed up for over four years without transfusion or recurrence of spinal cord compression. Discussion: Extramedullary hematopoiesis should be investigated in patients with hematologic disorders and spinal cord symptoms. The rapid recognition and treatment with radiotherapy can dramatically alleviate symptoms.

Hb Köln [alfa2ß298(FG5) val-met] identified by DNA analysis in a Brazilian family

Hb Köln resulta da substituiçäo do aminoácido valina por metionina na posiçäo 98 da cadeia da hemoglobina. Embora seja a mais freqüente das hemoglobinas instáveis, possui poucas características que permitem distinguí-las sem a realizaçäo de análise estrutural da molécula. Com o objetivo de desenvolver um procedimento alernativo a análise proteíca, este trabalho descreve a identificaçäo da Hb Köln através de análise de DNA. Uma paciente branca, sexo feminino, 4 anos de idade, com icterícia desde o nascimento, foi analisada, apresentando uma banda anômala entre A2 e S em eletroforese em acetato de celulose, e migraçäo eletroforética semelhante a Hb C em gel de agar. Os testes de instabilidade térmica e de precipitaçäo pelo isopropanol foram positivos e foram observados corpúsculos de Heinz no sangue periférico. Os três exons do gene da globina foram seqüenciados e uma transiçäo de G A foi identificada na primeira posiçäo do codon 98. Essa alteraçäo näo cria ou abole nenhum sítio conhecido de enzima de restriçäo. Desta forma, a confirmaçäo da mutaçäo foi levada a efeito através de hibridizaçäo com oligonucleotídeos alelo-específicos, o que permitiu o estabelecimento de um método simples e rápido de identificaçäo de novos casos quando os dados clínicos e o padräo hematológico e eletroforético sugerem Hb Köln.

Paracoccidioidomicose na infancia: relato de caso e revisao da literatura / Paracoccidioidomycosis in the childhood: relate of case and review of literature

Paracoccidioidomicose e uma doenca granulomatosa cronica,pouco frequente na infancia. Os autores relatam caso de menino de 4 anos com a forma linfoganglionar da doenca, em tratamento com sulfadiazina. Em revisao da literatura da ultima decada foram encontrados 45 casos de pacientes menores de 18 anos sendo 6 menores de 6 anos, destes 5 com descricao completa: 4 com febre, 3 com adenopatia e hepatoesplenomegalia, 4 com osteolise, 2 com lesao de pele. O tratamento variou entre Anfotericina B, Ketoconazol, Sulfa e Contrimoxazol. Um paciente evoluiu para obito (letalidade de 20%). Os autores comentam a historia natural da doenca, diagnostico e tratamento .