Clinical and hematological profile in a newborn cohort with hemoglobin SC / Perfil clínico e hematológico em uma coorte neonatal com hemoglobina SC

Abstract Objectives: Hemoglobin SC is the second most common variant of sickle-cell disease worldwide, after hemoglobin SS. The objectives of the study were to describe the clinical and laboratory characteristics of hemoglobin SC disease in children from a newborn screening program and treated at a blood center. Methodology: This study assessed a cohort of 461 infants born between 01/01/1999 and 12/31/2012 and followed-up until 12/31/2014. Clinical events were expressed as rates for 100 patient-years, with 95% confidence intervals. Kaplan-Meier survival curves were created. Results: The median age of patients was 9.2 years; 47.5% were female. Mean values of blood tests were: hemoglobin, 10.5 g/dL; reticulocytes, 3.4%; white blood cells, 11.24 × 109/L; platelets, 337.1 × 109/L; and fetal hemoglobin, 6.3%. Clinical events: acute splenic sequestration in 14.8%, blood transfusion 23.4%, overt stroke in 0.2%. The incidence of painful vaso-occlusive episodes was 51 (48.9-53.4) per 100 patient-years and that of infections, 62.2 episodes (59.8-64.8) per 100 patient-years. Transcranial Doppler ultrasonography (n = 71) was normal given the current reference values for SS patients. Hydroxyurea was given to ten children, all of whom improvement of painful crises. Retinopathy was observed in 20.3% of 59 children who underwent ophthalmoscopy. Avascular necrosis was detected in seven of 12 patients evaluated, predominantly in the left femur. Echocardiogram compatible with pulmonary hypertension was recorded in 4.6% of 130 children, with an estimated average systolic pulmonary artery pressure of 33.5 mmHg. The mortality rate from all causes was 4.3%. Conclusions: Clinical severity is variable in SC hemoglobinopathy. Several children have severe manifestations similar to those with SS disease.

Resumo Objetivos: A hemoglobinopatia SC é a segunda variante mais comum da doença falciforme no mundo, após a hemoglobinopatia SS. Os objetivos do estudo foram descrever as características clínicas e laboratoriais da hemoglobinopatia SC em recém-nascidos diagnosticados por programa de triagem neonatal e encaminhados para acompanhamento em hemocentro. Metodologia: Coorte de 461 recém-nascidos SC nascidos entre 01/01/1999 e 31/12/2012 e seguidos até 31/12/2014. A incidência de eventos clínicos foi expressa por taxas relativas a 100 pacientes-ano, com limites de confiança a 95%. Curvas de sobrevida foram construídas segundo Kaplan-Meier. Resultados: Mediana de idade, 9,2 anos; 47,5%, feminino. Médias dos valores hematológicos: hemoglobina 10,5 g/dL; reticulócitos 3,4%; leucometria 11,24 x 109/L; plaquetometria 337,1x109/L; hemoglobina fetal 6,3%. Eventos clínicos: sequestro esplênico agudo em 14,8%, hemotransfusão 23,4%, AVC isquêmico 0,2%. A incidência de episódios vaso-oclusivos dolorosos foi de 51 (48,9-53,4) por 100 pacientes-ano; a de infecções, 62,2 episódios (59,8-64,8) por 100 pacientes-ano. Doppler transcraniano (n = 71) foi normal, se usados os valores de referência de crianças SS. Dez pacientes usaram hidroxiureia, todos com melhoria das crises dolorosas. Retinopatia foi observada em 20,3% das 59 crianças que fizeram fundoscopia. Necrose avascular foi detectada em 7 de 12 pacientes avaliados, com predomínio no fêmur esquerdo. Ecocardiograma compatível com hipertensão pulmonar foi registrado em 4,6% de 130 crianças, com média estimada de 33,5 mm Hg de pressão arterial pulmonar. A taxa de mortalidade por todas as causas foi de 4,3%. Conclusões: A hemoglobinopatia SC tem gravidade variável; várias crianças apresentam manifestações clínicas intensas, semelhantes às da hemoglobinopatia SS.

Bone marrow necrosis and fat embolism syndrome: a dreadful complication of hemoglobin sickle cell disease

Sickle cell disease encompasses a wide range of genotypic presentation with particular clinical features. The entity affects millions of people, particularly those whose ancestors came from sub-Saharan Africa and other countries in the Western Hemisphere, Saudi Arabia, and India. Currently, the high frequency of S and C genes reflects natural selection through the protection of heterozygotes against severe malaria, the high frequency of consanguineous marriages, improvement of some public health policies and the nutritional standards in the poorer countries where newborns are now living long enough to present for diagnosis and management. Although there is a high burden of the disease, in many countries, the new-born sickle cell screening test is being performed and is rendering an early diagnosis; however, it is still difficult for sickle cell patients to find proper treatment and adequate follow-up. Moreover, in many countries, patients are neither aware of their diagnosis nor the care they should receive to prevent complications; also, they do not receive adequate genetic counseling. Hemoglobin SC (HbSC) disease is the most frequent double sickle cell heterozygosis found in Brazil. The clinical course tends to be more benign with fewer hospitalizations compared with double homozygotic SS patients. However, HbSC patients may present severe complications with a fatal outcome. We report the case of a 36-year-old man who presented to the emergency care facility with symptoms consistent with the diagnosis of sickling crisis. The outcome was unfavorable and death occurred just hours after admission. The autopsy revealed a generalized vaso-occlusive crisis by sickled red cells, bone marrow necrosis, and fat embolism syndrome.

Velocidade de fluxo sanguíneo cerebral em crianças em crianças e adolescentes com doença falciforme em Salvador, Bahia / Cerebral blood flow velocity in children and adolescents with sickle cell disease in Salvador, Bahia

INTRODUÇÃO: A doença falciforme (DF) é caracterizada por complicações agudas e crônicas. Entre as agudas podemos citar: episódios álgicos, síndrome torácica aguda (STA), priapismo, crise hemolítica, infecções agudas e acidente vascular cerebral (AVC), sendo este útimo responsavel por complicações a longo prazo na infância. A velocidade do fluxo sanguíneo cerebral (VFSC) elevada é o fator de risco mais importante para o desenvolvimento do AVC em crianças com anemia falciforme. A identificação de pacientes de risco associados a velocidades de fluxo sanguíneos cerebrais anormais é realizada pelo Doppler transcraniano (DTC), exame fundamental à prevenção primária do AVC. OBJETIVOS: Avaliar as velocidades de fluxo sanguíneo cerebral em crianças e adolescentes com DF em Salvador-Bahia, para identificar aqueles com risco alto de AVC, além de correlacionar as velocidades de fluxo cerebral com os perfis clínico e hematológico dos pacientes. PACIENTES E MÉTODOS: O DTC por insonação, utilizando uma sonda de 2 MHZ...

BACKGROUND: Sickle cell disease (SCD) is characterized by acute episodes of illnesses (crises) such as bone pain crisis, acute chest syndrome (ACS), priapism, hemolytic crisis, acute infections; and acute and long term complications such as cerebrovascular accident (CVA). Abnormally high cerebral blood flow velocity is the most important risk factor for development of stroke in pediatric patients with sickle cell anemia, and its detection by transcranial Doppler (TCD) is fundamental in primary stroke prevention. Other clinical, hematologic and genetic risk factors of stroke have also been identified. OBJECTIVES: The study aimed at evaluating the cerebral blood flow velocities of children and adolescents with SCD in Salvador, Brazil, detect those at high risk of stroke and correlate the flow velocities with clinical and hematological profiles of the patients. PATIENTS AND METHODS: Transcranial Doppler was performed on subjects aged 2 to 16 years who fulfilled the inclusion criteria, using a 2 MHz...

Acidente vascular cerebral na hemoglobinopatia SC(HBB glu6val e glu6lys): avaliação de marcadores de prognóstico / hemoglobinopathy (HBB glu6val and glu6lys): evaluation of prognostic markers

O acidente vascular cerebral (AVC) é uma complicação clínica grave da doença falciforme (DF). Poucos estudos avaliaram a velocidade do fluxo sanguíneo cerebral utilizando o Doppler transcraniano (DTC) e marcadores preditores do AVC na hemoglobinopatia SC (HbSC) e, desta forma, as velocidades consideradas de risco para os indivíduos com esta hemoglobinopatia são baseadas em velocidades descritas para a anemia falciforme (AF) e para a Sβ talassemia (HbS/β). Assim, o objetivo do presente estudo foi identificar marcadores preditores do AVC em indivíduos com HbSC, estabelecendo subfenótipos da doença pela associação de biomarcadores genéticos, hematológicos, bioquímicos e imunológicos com o valor da velocidade do fluxo sanguíneo cerebral. Para tanto, foi realizado um estudo transversal, onde foram investigados 68 indivíduos com HbSC. A velocidade média máxima do fluxo sanguíneo cerebral nas artérias cerebral média, carótida anterior e cerebral anterior foi determinada utilizando o DTC...

Stroke is a serious clinical complication of sickle cell disease (SCD). Only few studies have evaluated the rate of cerebral blood flow by transcranial Doppler (TCD) and stroke predictor markers on hemoglobinopathy SC (HbSC), thus, velocity considered as risk for stroke that is used to diagnose HbSC individuals are based on velocities described for the sickle cell anemia (SCA) and Sβ thalassemia. The objective of this study was to identify predictors markers of stroke in individuals with HbSC, establishing subphenotypes disease by the association of genetic biomarkers, hematological, biochemical and immunological with the value of the velocity of cerebral blood flow. For that, we conducted a cross-sectional study, which were investigated 68 HbSC individuals. The average maximum rate of cerebral blood flow in the middle cerebral artery, anterior cerebral artery and anterior carotid artery was determined using the DTC...

Protocolo para portadores de síndromes falciformes / Protocol for management of patients with sickle cell syndrome

Este protocolo aborda pacientes, crianças e adultos, portadores de Síndromes Falciformes, definidos como tendo em comum a herança do gen da globina beta falciforme (HBS). Inclui, portanto, as hemoglobinopatias SS, SC, S beta O e S beta + talassemia. Visa uma uniformizaçäo de condutas, proporcionando um melhor atendimento desses pacientes, bem como a realizaçäo de estudos prospectivos e retrospectivos.