title: Reticulocyte count is the most important predictor of acute cerebral ischemia and high-risk transcranial Doppler in a newborn cohort of 395 children with sickle cell anemia.
abstract: Stroke is a severe clinical manifestation of sickle cell anemia (SCA). Despite the prognostic relevance of transcranial Doppler (TCD), more accurate tools to assess stroke risk in children with SCA are required. Here, we describe the effect of clinical, laboratory, and molecular features on the risk of stroke and high-risk TCD in children from the newborn cohort of Minas Gerais, Brazil. Outcomes studied were acute cerebral ischemia and high-risk TCD. Clinical and hematological data were retrieved from children's records. Genetic markers, which were known for their association with stroke risk, were genotyped by polymerase chain reaction/restriction fragment length polymorphism and sequencing. The cumulative incidence of acute cerebral ischemia by the age of 8 years was 7.4 % and that of high-risk TCD by the age of 11.5 years was 14.2 %. The final multivariate model for acute cerebral ischemia risk included high white blood cell count and reticulocyte count, acute chest syndrome rate, and the single nucleotide polymorphisms (SNPs) TEK rs489347 and TNF-α rs1800629. The model for high-risk TCD included high reticulocyte count and the SNPs TEK rs489347 and TGFBR3 rs284875. Children with risk factors should be considered for intensive risk monitoring and for intervention therapy.
authors: Centro de Tecidos Biológicos de Minas Gerais, Fundação Hemominas, Rua das Goiabeiras, 779, Lagoa Santa, Minas Gerais, 33400-000, Brazil. andrebelisario@yahoo.com.br.|Faculdade de Medicina/NUPAD, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. andrebelisario@yahoo.com.br.
authors: André Rolim
authors: AR
authors: Belisário
authors: Serviço de Pesquisa, Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil.
authors: Rahyssa Rodrigues
authors: RR
authors: Sales
authors: Serviço de Pesquisa, Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil.
authors: Nayara Evelin
authors: NE
authors: Toledo
authors: Faculdade de Medicina/NUPAD, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors: Maristela Braga de Sousa Rodrigues
authors: MB
authors: Muniz
authors: Departamento Básico-Área de Saúde, Universidade Federal de Juiz de Fora (UFJF), Governador Valadares, Minas Gerais, Brazil.
authors: Cibele
authors: C
authors: Velloso-Rodrigues
authors: Serviço de Pesquisa, Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil.
authors: Célia Maria
authors: CM
authors: Silva
authors: Faculdade de Medicina/NUPAD, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors: Marcos Borato
authors: MB
authors: Viana
mesh_terms: D056586:Acute Chest Syndrome / Q000209:etiology; D000208:Acute Disease; D000755:Anemia, Sickle Cell / Q000150:complications*; D002545:Brain Ischemia / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007958:Leukocyte Count; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011509:Proteoglycans / Q000235:genetics; D042787:Receptor, TIE-2 / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D017701:Reticulocyte Count; D012306:Risk; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D017585:Ultrasonography, Doppler, Transcranial; D055544:beta-Globins / Q000235:genetics
chemical_list: D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D055544:beta-Globins; C071736:betaglycan; D042787:Receptor, TIE-2
keywords: Prognosis; Risk factors; Sickle cell anemia; Stroke; Transcranial Doppler ultrasound