Survival Probability in Patients with Sickle Cell Anemia Using the Competitive Risk Statistical Model.

The clinical picture of patients with sickle cell anemia (SCA) is associated with several complications some of which could be fatal. The objective of this study is to analyze the causes of death and the effect of sex and age on survival of Brazilian patients with SCA. Data of patients with SCA who were seen and followed at HEMORIO for 15 years were retrospectively collected and analyzed. Statistical modeling was performed using survival analysis in the presence of competing risks estimating the covariate effects on a sub-distribution hazard function. Eight models were implemented, one for each cause of death. The cause-specific cumulative incidence function was also estimated. Males were most vulnerable for death from chronic organ damage (p = 0.0005) while females were most vulnerable for infection (p=0.03). Age was significantly associated (p ≤ 0.05) with death due to acute chest syndrome (ACS), infection, and death during crisis. The lower survival was related to death from infection, followed by death due to ACS. The independent variables age and sex were significantly associated with ACS, infection, chronic organ damage and death during crisis. These data could help Brazilian authorities strengthen public policies to protect this vulnerable population

Mortality in children, adolescents and adults with sickle cell anemia in Rio de Janeiro, Brazil.

OBJECTIVE: To determine the mortality rate of children, adolescents and adults with sickle cell anemia in Rio de Janeiro, Brazil. METHODS: The number of deaths, the mortality rate and the causes of deaths in patients with sickle cell anemia who were treated and followed up at our institution for 15 years were determined and compared to data available for the Brazilian population. RESULTS: The overall number of deaths was 281 patients with a mortality rate of 16.77%. Survival probability was significantly higher in females. The number of deaths and the mortality rate were age-specific with a significant increase in the 19- to 29-year-old age group. The remaining life expectancy of the patients with sickle cell anemia was less than that of Brazilians at large. The gap between the two was about 20 years for ages between one and five years with this gap decreasing to ten years after the age of 65 years. The most common causes of death were infection, acute chest syndrome, overt stroke, organ damage and sudden death during painful crises. CONCLUSION: To the best of our knowledge, this is the first Brazilian study in a single institution in Rio de Janeiro; the mortality rate was 18.87% among adult patients with sickle cell anemia. The mortality rates in children and adults are higher than those reported in developed countries of the northern hemisphere

Doença falciforme: influência da adoção de intervenções em saúde pública

São abordados três aspectos da atenção à doença falciforme (DF): 1. Triagem Neonatal. Avaliou-se a eficácia dos primeiros 10 anos do Programa de Triagem Neonatal para hemoglobinopatias na identificação e tratamento das crianças com doença falciforme. Amostras de sangue de 1.217.833 recém-nascidos foram analisadas por cromatografia líquida de alta resolução. Os dados mostraram que 4,9% dos recém-nascidos foram heterozigotos para alguma variante de hemoglobina, 0,1% eram homozigotos ou duplamente heterozigotos para a hemoglobina anormal e 95% tinham hemoglobina normal. Todos os 912 recém-nascidos com DF foram encaminhados para o HEMORIO. Trinta e quatro (3,7%) faleceram devido à septicemia, síndrome torácica aguda ou sequestro esplênico; quatro, de causas desconhecidas. Este estudo mostrou que o diagnóstico e tratamento precoces dos recém-nascidos foram associados com melhora da sobrevida. 2. Uso da Hidroxicarbamida. Embora exista evidência de que a hidroxicarbamida reduza a mortalidade entre os adultos com DF, não havia relatos sobre o efeito da HU na mortalidade entre crianças. Nosso programa foi estabelecido para tratar pacientes com idades entre 3-18 anos que preenchessem os critérios de gravidade estabelecidos pelo Ministério da Saúde. Os dados de mortalidade e efeitos clínicos/laboratoriais da HU foram coletados retrospectivamente nos primeiros 9 anos do programa. A mortalidade entre os que receberam hidroxicarbamida foi comparada com a das crianças não tratadas. Entre os 1760 pacientes, 267 receberam hidroxicarbamida numa dose média de 20,8 mg/kg/d (10-32 mg) por 2 anos em média (0,1-6,5). A sobrevida nas crianças tratadas foi significativamente maior do que nas não tratadas (99,5% vs. 94,5%, P=0,01). A terapia com HU foi associada com aumentos da concentração de hemoglobina, da hemoglobina fetal, do volume corpuscular médio e com reduções do número de plaquetas, reticulócitos e neutrófilos. Foram observados significativamente menos atendimentos de emergência além de diminuição no número e duração das internações entre os indivíduos tratados com HU. A terapia com HU resultou em melhora do curso clínico e diminuição da mortalidade entre as crianças com doença falciforme. 3. Hipertensão pulmonar. Foi realizado um estudo de coorte prospectivo com 125 pacientes com anemia falciforme entre as idades de 16 a 60 anos que foram acompanhados por 15 meses. Dados demográficos, clínicos e de exames complementares foram analisados. Velocidades de regurgitação tricúspide (TRJV) 3,0 m/s, substancialmente elevadas. Pacientes com TRJV anormal eram significativamente mais velhos e mais anêmicos, tinham níveis de desidrogenase lática (LDH) e contagem de reticulócitos significativamente maiores e menor taxa de sobrevida. No modelo multivariado, a idade, com ponto de corte de trinta e dois anos, foi a covariável que mais influenciou o resultado da TRJV. A sobrevida para pacientes com creatinina (Cr) >1,0 mg/dl foi menor do que aquela no grupo com Cr ≤1 mg/dl e TRJV normal. Dez pacientes morreram durante o acompanhamento, 7 dos quais com TRJV >2,5 m/s. A síndrome torácica aguda foi a causa mais comum de morte seguida de septicemia. Este estudo mostra que pacientes HbSS com idade >32 anos, LDH alta, TRJV elevada, anemia mais grave e Cr >1 mg/dl têm prognóstico reservado e podem estar em risco de desenvolver hipertensão pulmonar devendo ser submetidos a cateterismo direitoThree aspects of sickle cell disease (SCD) were addressed: 1. Newborn Screening. The effectiveness of the first 10 years of the Newborn Screening Program for hemoglobinopathies in identifying and managing infants with sickle cell disease was evaluated. Blood samples from 1,217,833 neonates were analyzed by High Performance Liquid Chromatography. Data showed that 4.9% of the newborns were heterozygous for hemoglobin variant, 0.1% homozygous or doubly heterozygous for abnormal hemoglobins, and 95.0% had normal hemoglobin. All the 912 newborns with SCD were referred to HEMORIO. Thirty-four (3.7%) died of sepsis, acute chest syndrome or splenic sequestration; four of unknown causes. This 10-year study showed that early diagnosis and treatment of newborns was associated with improved survival of children with SCD. 2. Use of Hydroxycarbamide. Although evidence is accumulating that HU decreases mortality among adults with sickle cell disease, there were no published data regarding the effect of HU on mortality among children. Our Program was established to treat children aged 3–18 years if they met disease severity criteria according to the Ministry of Health. Mortality data and clinical/laboratorial effects of hydroxycarbamide were retrospectively collected for the first 9 years of the Program. Mortality among those receiving HU was compared to that of untreated children. Among 1760 subjects, 267 received HU at a median dose of 20.8 mg/kg/d (range 10–32) for a median of 2 years (range 0.1–6.5). Survival among HU-treated children was significantly greater than that among untreated ones (99.5% vs. 94.5%, P = 0.01). HU therapy was significantly associated with increases in haemoglobin concentration, fetal haemoglobin, mean corpuscular volume, and reduction in platelet counts, reticulocytes and neutrophils. Significantly fewer hospitalizations and emergency room visits, and shorter admissions were observed among HU-treated subjects.HU therapy reduced disease severity and was associated with decreased mortality among children with SCD. 3. Pulmonary Hypertension. We conducted a prospective cohort study of 125 patients with sickle cell anemia (HbSS) between the ages of 16 to 60 years. Enrolled patients were followed-up prospectively for 15 months. Demographic, clinical, and laboratory data were obtained. A tricuspid regurgitant jet velocity (TRJV) 3.0 m/sec, severe. Patients with abnormal TRJV were significantly older and more anemic, had significantly higher lactate dehydrogenase (LDH) levels, reticulocyte count and incidence of death. In the logistic multivariate model, age was the covariate that most influenced the outcome of normal or abnormal TRJV with a cutoff of thirty-two years. The survival rate for the group of patients with creatinine (Cr) >1.0 mg/dL was lower than the group with Cr ≤1 mg/dL and normal TRJV. Ten patients died during the follow-up of whom 7 had TRJV >2.5 m/sec. Acute chest syndrome was the most common cause of death followed by sepsis. This study shows that patients with HbSS older than thirty-two years with high LDH, elevated TRJV, more severe anemia and Cr >1 mg/dl have poor prognosis, may be at risk of having pulmonary hypertension and should undergo right heart catheteris

Menopause in Brazilian women with sickle cell anemia with and without hydroxyurea therapy.

Women with sickle cell anemia (SCA) require special attention for myriad obstetric and gynecologic issues associated with this complex hematologic disorder. These affect all aspects of female life from menarche through menopause. Information regarding obstetric and gynecologic complications of sickle cell disease (SCD), with a few exceptions, is based primarily on observational, anecdotal, retrospective, or cohort studies that may not reflect current aspects of obstetric care.1 Similarly, there are no recent reports about menopause (also known as climacteric) in women with SCA. The fact that life expectancy of women with SCA was determined to be 46–48 years2 delayed studies about menopause. The recent improved survival of patients with SCA resulted in women reaching the age that is usually associated with the onset of menopause. The purpose of this letter is to determine if the onset of menopause is early or late in women with SCA and if hydroxyurea affects the onset of menopause

Triagem neonatal para hemoglobinopatias no Rio de Janeiro, Brasil Neonatal screening for hemoglobinopathies in Rio de Janeiro, Brazil

OBJETIVO: Descrever os principais resultados do programa de triagem neonatal para a doença falciforme do Estado do Rio de Janeiro em 15 meses de funcionamento (agosto de 2000 a novembro de 2001). MÉTODOS: A partir de agosto de 2000, amostras de sangue passaram a ser coletadas de todos os recém-nascidos atendidos em postos de atenção básica à saúde no Estado para triagem neonatal da doença falciforme. Essas amostras são submetidas a cromatografia líquida de alta resolução. Se o cromatograma resultante for compatível com a doença falciforme, a criança e seus pais são encaminhados para confirmação diagnóstica e tratamento. RESULTADOS: De agosto de 2000 a novembro de 2001, 99 260 recém nascidos participaram da triagem. Houve um caso de homozigose para Hb C. Um em cada 27 recém-nascidos triados pelo programa apresentou o traço falciforme (Hb AS). A doença falciforme foi constatada em 83 casos (um caso novo para cada 1 196 nascimentos): 62 Hb S, 18 Hb SC, 3 Hb SD. Uma criança não compareceu para confirmação diagnóstica. As 82 crianças acompanhadas apresentaram 15 intercorrências (infecções de vias aéreas superiores, febre, seqüestro esplênico, síndrome mão-pé e crises de vaso-oclusão), motivando sete internações. Houve necessidade de transfusão sangüínea em 15 crianças, mas nenhuma tornou-se alo-imunizada. Os demais bebês estão evoluindo satisfatoriamente com o uso de penicilina profilática. CONCLUSÕES: Nossos dados evidenciam a importância do diagnóstico precoce da doença falciforme, de forma a prevenir e evitar as freqüentes complicações infecciosas enfrentadas por esses pacientes.<br>OBJECTIVE: To describe the main results obtained in the first 15 months of neonatal screening for sickle cell disease in the state of Rio de Janeiro, Brazil, from August 2000 to November 2001. METHODS: Starting in August 2000, blood samples began to be collected for sickle cell disease screening from all newborns receiving care in primary health care clinics in the state of Rio de Janeiro. The samples were submitted to high-resolution liquid chromatography. If the resulting chromatogram was compatible with sickle cell disease, the child and the parents were referred for diagnostic confirmation and treatment. RESULTS: Between August 2000 and November 2001, 99 260 newborns were screened. There was one case of homozygous Hb C. On average, one of every 27 newborns who were screened presented sickle cell trait (Hb AS). Sickle cell disease was observed in 83 cases, or one new case in each 1 196 births. The 83 consisted of: 62 Hb S, 18 Hb SC, and 3 Hb SD. One child did not appear for diagnostic confirmation. The 82 children who were followed up by the program presented 15 intercurrent illnesses (upper respiratory infections, fever, splenic sequestration crises, hand-foot syndrome, and vascular occlusion), resulting in seven hospital admissions. Blood transfusions were necessary with 15 children, but none developed alloimmunization. All the other babies were doing well with the use of prophylactic penicillin. CONCLUSIONS: Our data show the importance of early diagnosis for sickle cell disease, so as to prevent the frequent infectious complications faced by these patients

Severity of Brazilian sickle cell disease patients: severity scores and feasibility of the Bayesian network model use

The integration of the several clinical and laboratory dimensions and the influence of each parameter on the sickle cell disease (SCD)-related mortality is useful for predicting the phenotype of an individual. This study evaluated the feasibility of the SCD severity calculator use to measure disease severity in Brazilian patients. The study group was composed of 500 SCD patients (440 HbSS and 60 HbSC) diagnosed by molecular biology. We observed a decrease in severity scores in 72 SCD patients assessed before and after the hydroxyurea (HU) use. Furthermore, the HU influenced the increase of mean corpuscular volume (MCV) and HbF concentration, and the decrease of leukocytes and total bilirubin. We found 180 (36.0%) patients with intermediate phenotype, 170 (34.0%) mild phenotype and 150 (30.0%) with severe phenotype. Patients with ages &gt;40 years had higher mean score (0.778 +/- 0.177) than patients between 18 and 40 years (0.562 +/- 0.152) and patients between 5 and 17 years (0.322 +/- 0.145). We observe that there is a tendency of individuals with leg ulcers, avascular necrosis and cardiac complications with increasing age. Correlation analysis showed relations between severity scores with leukocytes, reticulocytes, bilirubin, lactate dehydrogenase, HbS, hemoglobin and hematocrit (p &lt; 0.05). Several comparisons involving age groups, SCD genotype and phenotypic classification had satisfactory results and this classification will be used for future studies involving genetic polymorphisms, response to treatment with HU and oxidative stress markers in SCD.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Risk Factors of Pulmonary Hypertension in Brazilian Patients with Sickle Cell Anemia.

This study was a prospective cross-sectional cohort study of 125 patients with sickle cell anemia (SS) between the ages of 16 to 60 years. Enrolled patients were followed-up prospectively for 15 months. Demographic, clinical, hematological and routine biochemical data were obtained on all patients. Six-minute walk test and Doppler Echocardiography were performed on all patients. A tricuspid regurgitant jet velocity (TRJV) 3.0 m/sec, severe. Patients with abnormal TRJV were significantly older and more anemic, had significantly higher lactate dehydrogenase (LDH) levels, reticulocyte count and incidence of death. The logistic multimodal model implemented for the 125 patients indicated that age was the covariate that influenced the outcome of normal or abnormal TRJV with a cutoff age of thirty-two years. The survival rate for the group of patients with creatinine (Cr) > 1.0 mg/dL was lower than the group with Cr ≤ 1 and normal TRJV. A coefficient matrix showed that the LDH values were weakly correlated with the reticulocyte count but strongly correlated with hemoglobin suggesting that the TRJV values were not correlated with the hemolytic rate but with anemia. Ten patients died during the follow-up of whom 7 had TRJV > 2.5 m/sec. Acute chest syndrome was the most common cause of death followed by sepsis. In conclusion, this study shows that patients with SS older than thirty-two years with high LDH, elevated TRJV, severe anemia and Cr > 1 have poor prognosis and may be at risk of having pulmonary hypertension and should undergo RHC