Mortality trends and sociodemographic factors associated with early death in sickle cell disease patients in the state of São Paulo.

OBJECTIVE: To estimate trends in mortality rate and average age of death, and identify sociodemographic factors associated with early death in patients with sickle cell disease (SCD). METHODS: An ecological and cross-sectional study was conducted using data from the Mortality Information System. All deaths of patients residing in the state of São Paulo from 1996 to 2015 with at least one International Disease Code for SCD in any field of the death certificate were included. Simple linear regression was used to estimate trends. The Log-rank test and multiple Cox regression were used to identify factors associated with early death. RESULTS: The age-standardized mortality rate per million inhabitants increased by 0.080 per year (R2=0.761; p<0.001). When the events were stratified by age at death, the increase was 0.108 per year for those occurring at age 20 years or older, (R2=0.789; p<0.001) and 0.023 per year for those occurring before age 20 years old (R2=0.188; p=0.056). The average age at death increased by 0.617 years (7.4 months) per year (R2=0.835; p<0.001). Sociodemographic factors associated with early death identified were male gender (hazard ratio - HR=1.30), white race (HR=1.16), death occurring in the hospital (HR=1.29), and living in the Greater São Paulo (HR=1.13). CONCLUSIONS: The mortality rate and the average age of death in patients with SCD have increased over the last two decades. Sociodemographic factors such as gender, race, place of occurrence, and residence were found to be associated with early death.

Thrombotic microangiopathy in patients with sickle cell disease.

OBJECTIVE: To describe two cases of patients who had thrombotic microangiopathy (TMA) associated with sickle cell disease (SCD). CASE DESCRIPTION: Both patients started with a painful crisis and had acute chest syndrome during hospitalization. They showed significant worsening of hemolytic anemia, with very high levels of lactate dehydrogenase, thrombocytopenia, lowered level of consciousness, organ damage and the presence of schistocytes in peripheral blood. Due to the possibility of TMA, despite the very rare association with SCD, they were treated with fresh frozen plasma replacement and plasmapheresis, with good response. COMMENTS: TMA is a serious, life-threatening disease, characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. The association of SCD and TMA is difficult to diagnose, since they can share a similar clinical presentation. Recognizing this association and promptly instituting treatment may impact the survival of these patients.

Consensus of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) and the Brazilian Ministry of Health - General management of blood and blood products on the tests necessary for the release of exceptional medicines for sickle cell disease.

To date, hydroxyurea is the only effective and safe drug that significantly reduces morbidity and mortality of individuals with Sickle cell disease. Twenty years of real-life experience has demonstrated that hydroxyurea reduces pain attacks, vaso-occlusive events, including acute chest syndrome, the number and duration of hospitalizations and the need for transfusion. The therapeutic success of hydroxyurea is directly linked to access to the drug, the dose used and adherence to treatment which, in part, is correlated to the availability of hydroxyurea. This consensus aims to reduce the number of mandatory exams needed to access the drug, prioritizing the requesting physician's report, without affecting patient safety.

Factors related to the readiness of Brazilian chronic pediatric patients to transition to care in adult clinics

Abstract Objective Advances in medicine have increased the life expectancy of pediatric patients with chronic illnesses, and challenges with the guided transition of adolescents and young adults from pediatric clinics to adult clinics have grown. The aim of this study was to better understand readiness and factors related to this transition process in Brazil. Method In this cross-sectional study of 308 patients aged from 16 to 21 years under follow-up in pediatric specialties, the degree of readiness for transition was assessed using the Transition Readiness Assessment Questionnaire (TRAQ) and its domains. Associations with demographic data, clinical data, socio-economic level, medication adherence, family functionality, and parental satisfaction with health care were evaluated. Results The median TRAQ score was 3.7 (3.2 - 4.2). Better readiness was associated with female patients, socio-economic class A-B, current active employment, higher level of education, not failing any school year, attending medical appointments alone, functional family, and a good knowledge of disease and medications. A low correlation was observed between TRAQ and age. TRAQ presented good internal consistency (alpha-Cronbach 0.86). In the multiple linear regression, TRAQ score showed a significant association with female gender, advanced age, socio-economic class A-B, better knowledge of disease and medications, and independence to attend appointments alone. Conclusion TRAQ instrument can guide healthcare professionals to identify specific areas of approach, in order to support adolescents with chronic disease to set goals for their own personal development and improve their readiness to enter into the adult healthcare system. In this study, some factors were related to better TRAQ scores.

Clinical and laboratory differences between pediatric hospitalized patients with sickle cell disease infected or not by SARS-CoV-2.

OBJECTIVE: The aim of this study was to identify clinical and complete blood count differences between pediatric hospitalized patients with sickle cell disease infected or not by SARS-CoV-2 and compare the complete blood count of patients with sickle cell disease infected by SARS-CoV-2 before hospitalization and on admission. METHODS: This study was a single-center prospective cohort. Data were collected from medical records of pediatric inpatients with sickle cell disease under 18 years old infected or not with SARS-CoV-2 from the first visit to the hospital until discharge and from the last medical appointment. All patients were tested for SARS-CoV-2 by the real-time reverse transcription polymerase chain reaction. RESULTS: Among 57 pediatric patients with sickle cell disease hospitalized from March to November 2020 in a Brazilian academic hospital, 11 (19.3%) had a positive result for SARS-CoV-2. Patients infected by SARS-CoV-2 had a higher prevalence of comorbidities than the ones who were not infected (63.6 vs. 30.4%; p=0.046). During hospital stay, no clinical or complete blood count differences between groups were found. There was a decrease in eosinophil count on hospital admission in patients with sickle cell disease infected by SARS-CoV-2 (p=0.008). CONCLUSIONS: Pediatric hospitalized patients with sickle cell disease infected by SARS-CoV-2 had more comorbidities and had a decrease in eosinophil count between hospital admission and the last medical appointment.

Factors related to the readiness of Brazilian chronic pediatric patients to transition to care in adult clinics.

OBJECTIVE: Advances in medicine have increased the life expectancy of pediatric patients with chronic illnesses, and challenges with the guided transition of adolescents and young adults from pediatric clinics to adult clinics have grown. The aim of this study was to better understand readiness and factors related to this transition process in Brazil. METHOD: In this cross-sectional study of 308 patients aged from 16 to 21 years under follow-up in pediatric specialties, the degree of readiness for transition was assessed using the Transition Readiness Assessment Questionnaire (TRAQ) and its domains. Associations with demographic data, clinical data, socio-economic level, medication adherence, family functionality, and parental satisfaction with health care were evaluated. RESULTS: The median TRAQ score was 3.7 (3.2 - 4.2). Better readiness was associated with female patients, socio-economic class A-B, current active employment, higher level of education, not failing any school year, attending medical appointments alone, functional family, and a good knowledge of disease and medications. A low correlation was observed between TRAQ and age. TRAQ presented good internal consistency (alpha-Cronbach 0.86). In the multiple linear regression, TRAQ score showed a significant association with female gender, advanced age, socio-economic class A-B, better knowledge of disease and medications, and independence to attend appointments alone. CONCLUSION: TRAQ instrument can guide healthcare professionals to identify specific areas of approach, in order to support adolescents with chronic disease to set goals for their own personal development and improve their readiness to enter into the adult healthcare system. In this study, some factors were related to better TRAQ scores.

Clinical and laboratory differences between pediatric hospitalized patients with sickle cell disease infected or not by SARS-CoV-2 / Diferenças clínicas e laboratoriais entre pacientes pediátricos hospitalizados com doença falciforme infectados ou não por SARS-CoV-2

Abstract Objective: The aim of this study was to identify clinical and complete blood count differences between pediatric hospitalized patients with sickle cell disease infected or not by SARS-CoV-2 and compare the complete blood count of patients with sickle cell disease infected by SARS-CoV-2 before hospitalization and on admission. Methods: This study was a single-center prospective cohort. Data were collected from medical records of pediatric inpatients with sickle cell disease under 18 years old infected or not with SARS-CoV-2 from the first visit to the hospital until discharge and from the last medical appointment. All patients were tested for SARS-CoV-2 by the real-time reverse transcription polymerase chain reaction. Results: Among 57 pediatric patients with sickle cell disease hospitalized from March to November 2020 in a Brazilian academic hospital, 11 (19.3%) had a positive result for SARS-CoV-2. Patients infected by SARS-CoV-2 had a higher prevalence of comorbidities than the ones who were not infected (63.6 vs. 30.4%; p=0.046). During hospital stay, no clinical or complete blood count differences between groups were found. There was a decrease in eosinophil count on hospital admission in patients with sickle cell disease infected by SARS-CoV-2 (p=0.008). Conclusions: Pediatric hospitalized patients with sickle cell disease infected by SARS-CoV-2 had more comorbidities and had a decrease in eosinophil count between hospital admission and the last medical appointment.

RESUMO Objetivo: Identificar diferenças clínicas e laboratoriais entre pacientes pediátricos hospitalizados com doença falciforme infectados ou não por SARS-CoV-2 e comparar o hemograma completo de pacientes com doença falciforme infectados por SARS-CoV-2 antes da hospitalização e durante a admissão. Métodos: Coorte prospectiva unicêntrica, cujos dados foram coletados em prontuários de pacientes pediátricos internados com doença falciforme, menores de 18 anos, infectados ou não com SARS-CoV-2, desde a primeira visita ao hospital até a alta e desde a última consulta médica. Todos os pacientes foram testados para SARS-CoV-2 pela transcrição reversa seguida de reação em cadeia da polimerase em tempo real. Resultados: Dos 57 pacientes pediátricos com doença falciforme internados de março a novembro de 2020 em um hospital universitário brasileiro, 11 (19,3%) apresentaram resultado positivo para SARS-CoV-2. Pacientes infectados pelo SARS-CoV-2 apresentaram maior prevalência de comorbidades do que aqueles não infectados (63,6 vs. 30,4%; p=0,046). Durante a internação hospitalar, não foram encontradas diferenças clínicas ou laboratoriais entre os grupos. Houve diminuição da contagem de eosinófilos na admissão hospitalar em pacientes com doença falciforme infectados pelo SARS-CoV-2 (p=0,008). Conclusões: Pacientes pediátricos hospitalizados com doença falciforme infectados pelo SARS-CoV-2 apresentaram mais comorbidades e diminuição da contagem de eosinófilos entre a admissão hospitalar e a última consulta médica.

Levels of angiotensin-converting enzyme 1 and 2 in serum and urine of children with Sickle Cell Disease / Níveis de enzima conversora da angiotensina 1 e 2 no soro e na urina de crianças com Doença Falciforme

Abstract Introduction: Sickle cell nephropathy begins in childhood and presents early increases in glomerular filtration, which, over the long term, can lead to chronic renal failure. Several diseases have increased circulating and urinary angiotensin-converting enzyme (ACE) activity, but there is little information about changes in ACEs activity in children with sickle cell disease (SCD). Objective: We examined circulating and urinary ACE 1 activity in children with SCD. Methods: This cross-sectional study compared children who were carriers of SCD with children who comprised a control group (CG). Serum and urinary activities of ACE were evaluated, as were biochemical factors, urinary album/creatinine rates, and estimated glomerular filtration rate. Results: Urinary ACE activity was significantly higher in patients with SCD than in healthy children (median 0.01; range 0.00-0.07 vs median 0.00; range 0.00-0.01 mU/mL·creatinine, p < 0.001. No significant difference in serum ACE activities between the SCD and CG groups was observed (median 32.25; range 16.2-59.3 vs median 40.9; range 18.0-53.4) mU/m`L·creatinine, p < 0.05. Conclusion: Our data revealed a high urinary ACE 1 activity, different than plasmatic level, in SCD patients suggesting a dissociation between the intrarenal and systemic RAAS. The increase of urinary ACE 1 activity in SCD patients suggests higher levels of Ang II with a predominance of classical RAAS axis, that can induce kidney damage.

Resumo Introdução: A nefropatia falciforme começa na infância e apresenta aumentos precoces na filtração glomerular, que, em longo prazo, podem levar à insuficiência renal crônica. Várias doenças têm aumentado a atividade da enzima conversora da angiotensina (ECA) urinária e circulante, mas há pouca informação sobre alterações na atividade das ECAs em crianças com doença falciforme (DF). Objetivo: Examinamos a atividade da ECA-1 circulante e urinária em crianças com DF. Métodos: Este estudo transversal comparou crianças que eram portadoras de DF com crianças que compunham um Grupo Controle (GC). As atividades séricas e urinárias da ECA foram avaliadas, assim como os fatores bioquímicos, a relação albumina/creatinina urinária e a taxa de filtração glomerular estimada. Resultados: A atividade urinária da ECA foi significativamente maior em pacientes com DF do que em crianças saudáveis (mediana 0,01; intervalo 0,00-0,07 vs mediana 0,00; intervalo 0,00-0,01 mU/mL·creatinina, p < 0,001. Não foi observada diferença significativa nas atividades séricas da ECA entre os grupos DF e GC (mediana 32,25; intervalo 16,2-59,3 vs mediana 40,9; intervalo 18,0-53,4) mU/mL·creatinina, p < 0,05. Conclusão: Nossos dados revelaram uma alta atividade urinária da ECA-1, diferente do nível plasmático, em pacientes com DF, sugerindo uma dissociação entre o Sistema Renina Angiotensina Aldosterona (SRAA) intra-renal e sistêmico. O aumento da atividade urinária da ECA-1 em pacientes com DF sugere níveis mais elevados de Ang II com predominância do eixo clássico do SRAA, que pode induzir lesão renal.

Levels of angiotensin-converting enzyme 1 and 2 in serum and urine of children with Sickle Cell Disease.

INTRODUCTION: Sickle cell nephropathy begins in childhood and presents early increases in glomerular filtration, which, over the long term, can lead to chronic renal failure. Several diseases have increased circulating and urinary angiotensin-converting enzyme (ACE) activity, but there is little information about changes in ACEs activity in children with sickle cell disease (SCD). OBJECTIVE: We examined circulating and urinary ACE 1 activity in children with SCD. METHODS: This cross-sectional study compared children who were carriers of SCD with children who comprised a control group (CG). Serum and urinary activities of ACE were evaluated, as were biochemical factors, urinary album/creatinine rates, and estimated glomerular filtration rate. RESULTS: Urinary ACE activity was significantly higher in patients with SCD than in healthy children (median 0.01; range 0.00-0.07 vs median 0.00; range 0.00-0.01 mU/mL·creatinine, p < 0.001. No significant difference in serum ACE activities between the SCD and CG groups was observed (median 32.25; range 16.2-59.3 vs median 40.9; range 18.0-53.4) mU/m`L·creatinine, p < 0.05. CONCLUSION: Our data revealed a high urinary ACE 1 activity, different than plasmatic level, in SCD patients suggesting a dissociation between the intrarenal and systemic RAAS. The increase of urinary ACE 1 activity in SCD patients suggests higher levels of Ang II with a predominance of classical RAAS axis, that can induce kidney damage.

Hemoglobinopathy and pediatrics in the time of COVID-19

ABSTRACT Introduction: It is important to know if patients with hemoglobinopathy could be more susceptible to COVID-19. Objective: Analyze SARS-CoV-2 infection in pediatric patients with hemoglobinopathy. Methods: Using the online platforms LILACS, PUBMED and EMBASE, on 17- JUL-2020 a search was made for the terms COVID-19 and SARS-CoV-2 associated with "sickle cell", "thalassemia" and "hemoglobinopathy". Results: There were 623 pediatric and adult patients with sickle cell disease (SCD) or beta thalassemia (BT) and COVID-19. Total mortality rate was 6.42%. No pediatric patient with BT has been described. So, our analysis focused on children and adolescents with SCD: there were 121 pediatric patients, one adolescent died, prophylactic anticoagulation was prescribed to six patients, 11.76% needed intensive care unit, blood transfusion was prescribed in 29.70%. Vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) were the main clinical manifestations in SCD. Discussion: Pediatric patients with SCD and COVID-19 have a low mortality rate when compared to adults, although is higher than the global pediatric population with COVID-19 (0−0.67%). The comorbidities associated with age and the long-term complications inherent to hemoglobinopathies may contribute to the increased mortality outside the pediatric age group. In SCD the clinical manifestations, both in children and adults, are VOC and ACS, and there was increase in blood requirement. Pediatric SCD patients with COVID-19 need more intensive care unit than the global pediatric population (3.30%). Conclusion: Despite pediatric population with SCD needs more intensive care, the outcome after infection by COVID-19 is favorable.

BEHAVIORAL CHARACTERISTICS OF CHILDREN WITH SICKLE CELL DISEASE.

OBJECTIVE: To evaluate sociodemographic and clinical aspects of children with sickle cell disease (SCD) and their behavioral characteristics. METHODS: Interview with parents of patients with SCD from four to ten years old, addressing socioeconomic aspects and other health conditions, and using the Strengths and Difficulties Questionnaire (SDQ). Clinical data were obtained from medical records. Exclusion criteria were the use of hydroxyurea, previous diagnosis of stroke, chronic encephalopathy and/or intellectual disability. RESULTS: 45 patients (19 girls and 26 boys) were assessed. The median age was seven years. Diagnosis of SCD: 26 hemoglobinopathy SC; 19 hemoglobinopathy SS. Socioeconomic class: D: 24.4%; C2: 44.4%; C1: 28.9%; B2: 2.2%. Clinical history: acute chest syndrome: 40%; transfusions: 66.7%; hospitalizations: 82.2%. SDQ findings: 88.9% clinical impact (emotional subscale: 68.9%); total score: impact in 48.9%. It was not possible to establish a relation between the severity of the disease and the results of the SDQ. Regarding socioeconomic class: among individuals of classes B2 and C1, 21.4% had impact at the total score; in classes C2 and D, this percentage was 61.3%. Regarding the schooling of the head of the family, with Elementary School at least, 39.3% of the children had impacts; for fewer education, this percentage was 64.7%. CONCLUSIONS: Behavioral impacts are highly prevalent in children with SCD. Individuals in socioeconomic classes C2 and D suffered more behavioral impacts than individuals in classes B2 and C1.

Hemoglobinopathy and pediatrics in the time of COVID-19.

INTRODUCTION: It is important to know if patients with hemoglobinopathy could be more susceptible to COVID-19. OBJECTIVE: Analyze SARS-CoV-2 infection in pediatric patients with hemoglobinopathy. METHODS: Using the online platforms LILACS, PUBMED and EMBASE, on 17- JUL-2020 a search was made for the terms COVID-19 and SARS-CoV-2 associated with "sickle cell", "thalassemia" and "hemoglobinopathy". RESULTS: There were 623 pediatric and adult patients with sickle cell disease (SCD) or beta thalassemia (BT) and COVID-19. Total mortality rate was 6.42%. No pediatric patient with BT has been described. So, our analysis focused on children and adolescents with SCD: there were 121 pediatric patients, one adolescent died, prophylactic anticoagulation was prescribed to six patients, 11.76% needed intensive care unit, blood transfusion was prescribed in 29.70%. Vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) were the main clinical manifestations in SCD. DISCUSSION: Pediatric patients with SCD and COVID-19 have a low mortality rate when compared to adults, although is higher than the global pediatric population with COVID-19 (0-0.67%). The comorbidities associated with age and the long-term complications inherent to hemoglobinopathies may contribute to the increased mortality outside the pediatric age group. In SCD the clinical manifestations, both in children and adults, are VOC and ACS, and there was increase in blood requirement. Pediatric SCD patients with COVID-19 need more intensive care unit than the global pediatric population (3.30%). CONCLUSION: Despite pediatric population with SCD needs more intensive care, the outcome after infection by COVID-19 is favorable.

Behavioral characteristics of children with sickle cell disease / Características comportamentais de crianças com doença falciforme

ABSTRACT Objective: To evaluate sociodemographic and clinical aspects of children with sickle cell disease (SCD) and their behavioral characteristics. Methods: Interview with parents of patients with SCD from four to ten years old, addressing socioeconomic aspects and other health conditions, and using the Strengths and Difficulties Questionnaire (SDQ). Clinical data were obtained from medical records. Exclusion criteria were the use of hydroxyurea, previous diagnosis of stroke, chronic encephalopathy and/or intellectual disability. Results: 45 patients (19 girls and 26 boys) were assessed. The median age was seven years. Diagnosis of SCD: 26 hemoglobinopathy SC; 19 hemoglobinopathy SS. Socioeconomic class: D: 24.4%; C2: 44.4%; C1: 28.9%; B2: 2.2%. Clinical history: acute chest syndrome: 40%; transfusions: 66.7%; hospitalizations: 82.2%. SDQ findings: 88.9% clinical impact (emotional subscale: 68.9%); total score: impact in 48.9%. It was not possible to establish a relation between the severity of the disease and the results of the SDQ. Regarding socioeconomic class: among individuals of classes B2 and C1, 21.4% had impact at the total score; in classes C2 and D, this percentage was 61.3%. Regarding the schooling of the head of the family, with Elementary School at least, 39.3% of the children had impacts; for fewer education, this percentage was 64.7%. Conclusions: Behavioral impacts are highly prevalent in children with SCD. Individuals in socioeconomic classes C2 and D suffered more behavioral impacts than individuals in classes B2 and C1.

RESUMO Objetivo: Avaliar aspectos sociodemográficos e clínicos de crianças com doença falciforme (DF) e suas características comportamentais. Métodos: Aplicação de entrevista sobre aspectos socioeconômicos e outras condições de saúde e do questionário de capacidades e dificuldades (SDQ) em pais de pacientes de quatro a dez anos com DF, em um ambulatório de referência. Dados clínicos foram obtidos dos prontuários médicos. Critérios de exclusão: uso de hidroxiureia, diagnóstico prévio de acidente vascular cerebral, encefalopatia crônica e/ou deficiência intelectual. Resultados: Analisados 45 pacientes (19 meninas e 26 meninos). Mediana de idade=7 anos. Diagnóstico da DF=26 hemoglobinopatia SC; 19 hemoglobinopatia SS. Classe econômica (SES): D=24,4%; C2=44,4%; C1=28,8%; B2=2,2%. Antecedentes clínicos: síndrome torácica aguda=40%; transfusões=66,7%; internações=82,2%. Achados SDQ=88,9% alteração clínica (subescala emocional=68,9%); pontuação total=alterada em 48,9%. Não foi possível estabelecer relação entre gravidade da doença e os resultados do SDQ. Com relação à SES, entre indivíduos das classes B2 e C1, 21,4% tiveram alteração na pontuação total; nas classes C2 e D, esse percentual foi de 61,3%. Quanto à escolaridade do chefe da família, com no mínimo ensino fundamental completo, 39,3% das crianças tiveram alteração; para menor escolaridade, esse percentual foi 64,7%. Conclusões: Alterações comportamentais são altamente prevalentes em crianças com DF. Indivíduos das classes C2 e D tiveram mais alterações comportamentais em relação aos indivíduos das classes B2 e C1.

Asthma, allergic sensitization and lung function in sickle cell disease.

BACKGROUND: Pulmonary disease is a frequent acute and chronic manifestation in sickle cell disease (SCD), presenting high morbidity and mortality. OBJECTIVES: To identify the prevalence and association of asthma, allergic sensitization and altered pulmonary function in patients with SCD (SS and Sßo). METHODS: A single-center, cross-sectional study was conducted, in which 70 patients with SCD and 44 controls, aged six to 18 years, responded to the questionnaire of the International Study of Asthma and Allergies in Childhood (ISAAC), complemented with an anamnesis regarding the associated clinical outcomes. All patients underwent immediate hypersensitivity skin tests with aeroallergens and a pulmonary function evaluation (spirometry). Regarding the statistical analysis, parametric and non-parametric methods were used, depending on the variables studied. Tests were considered significant when p<0.05. RESULTS: There was no significant difference between the patients and controls regarding the prevalence of asthma and allergic sensitization (p>0.05). The number of occurrences of acute chest syndrome per patient per year was significantly higher for asthmatic patients than for non-asthmatic patients (p=0.04). Obstructive pulmonary function occurred in 30.9% of the patients and in 5.4% of the controls, and restrictive pulmonary function occurred in 5.5% of the patients and 5.4% of the controls. Asthma and wheezing in the last 12months had significant associations with obstructive pulmonary function (p=0.014 and p=0.027, respectively). CONCLUSIONS: The occurrence of asthma, allergic sensitization and alteration in lung function in patients with SCD reinforces the importance of routine monitoring of these diagnoses, which allows for early treatment and prevention of the evolution of pulmonary disease in adulthood.