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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

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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.

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Acknowledgments

The authors acknowledge all subjects and parents for their cooperation in the study. The authors also thank the financial support of Fundação Hemominas, Núcleo de Ações e Pesquisa em Apoio Diagnóstico (Nupad-UFMG), Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG; grant no. PPM-00266-13), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; grant no. 304530/2011-5), and Coordenação deAperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Authors and Affiliations

  1. Centro de Tecidos Biológicos de Minas Gerais, Fundação Hemominas, Rua das Goiabeiras, 779, Lagoa Santa, Minas Gerais, 33400-000, Brazil

    André Rolim Belisário

  2. Faculdade de Medicina/NUPAD, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil

    André Rolim Belisário, Maristela Braga de Sousa Rodrigues Muniz & Marcos Borato Viana

  3. Serviço de Pesquisa, Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil

    Rahyssa Rodrigues Sales, Nayara Evelin Toledo & Célia Maria Silva

  4. Departamento Básico—Área de Saúde, Universidade Federal de Juiz de Fora (UFJF), Governador Valadares, Minas Gerais, Brazil

    Cibele Velloso-Rodrigues

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  1. André Rolim Belisário
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  2. Rahyssa Rodrigues Sales
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  3. Nayara Evelin Toledo
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Correspondence to André Rolim Belisário.

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Belisário, A.R., Sales, R.R., Toledo, N.E. et al. 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. Ann Hematol 95, 1869–1880 (2016). https://doi.org/10.1007/s00277-016-2789-5

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