Laboratory Biomarkers, Cerebral Blood Flow Velocity, and Intellectual Function in Children with Sickle Cell Disease.

Nataly Apollonsky,Deepti Raybagkar,Reem Tarazi,Norma B Lerner,Fengqing Zhang,Jennifer Eng

doi:10.1155/2020/8181425

Abstract

Objective The aim of this preliminary study was to describe putative markers of cerebral vasculopathy and investigate relationships among these markers, demographic factors, and cognitive function in a young sample of neurologically normal children with SCD. Study Design. Thirty-eight children with homozygous HbS, aged 4–11 years, were included. Estimated IQ and markers of coagulation and endothelial activation, hemolysis, and inflammation, as well as transcranial Doppler velocities, hydroxyurea use, and demographic information were obtained. Results Using multiple regression analyses, there were few significant independent associations between biomarkers or blood flow velocity and estimated IQ. Lactic dehydrogenase (LDH) independently predicted cognitive function, but blood flow velocity did not mediate this relationship. Maternal education, patient age, and hydroxyurea status were independent predictors of cognition. Given the small sample size, a LASSO statistical model was employed to further identify potential predictors of IQ, which identified LDH, absolute neutrophil count (ANC), platelet count, thrombin-antithrombin (TAT), tissue factor (TF), maternal education, age, and hydroxyurea as potential predictors of cognition. Conclusions In addition to effects of age and maternal education, some vasculopathic markers are associated with cognitive function in young children with SCD, and these relationships do not appear to be mediated through blood flow velocity. Although the lack of association among certain variables was not as predicted, results provide support for further research regarding the influence of vasculopathic markers on cognitive function in children with SCD without stroke, especially intravascular hemolysis and coagulation/endothelial activation, and a possible role for HU treatment in preventing or reversing cognitive decline.

Highlights

Sickle cell disease (SCD) is one of the most prevalent hematological genetic disorders, which could affect multiple organ systems, including the central nervous system (CNS)
Considering that the risk of cerebrovascular disease is high in very young children with SCD [1] and that cognitive function tends to decline in this population even in the absence of stroke [16], the purpose of this study is to investigate the potential relevance of markers of vasculopathy on cognitive function in a relatively young cohort of high-risk children with SCD. e study aims to evaluate if laboratory biomarkers are directly associated with general cognitive ability or if these relationships are mediated by cerebral blood flow velocity, measured by transcranial Doppler ultrasonography (TCD)
Hematologic and TCD data are presented in Table 1. e time-averaged maximum mean (TAMM) velocity represents the right or left middle cerebral artery (MCA) velocity in 84% of cases; for the remaining cases, the right or left internal carotid artery (ICA) value was included

Summary

Introduction

Sickle cell disease (SCD) is one of the most prevalent hematological genetic disorders, which could affect multiple organ systems, including the central nervous system (CNS). Most common CNS manifestations include overt and silent stroke and neurocognitive dysfunction. Silent cerebral infarctions are associated with small vessel disease and occur in up to 37% of children before the age of 14 [3]. Overt stroke risk can be demonstrated by elevation of blood flow velocity measured by transcranial Doppler ultrasonography (TCD). Since the publication of the Stroke Prevention Trial in Sickle Cell Anemia in 1998 and introduction of TCD screening, prophylactic blood transfusions, and hydroxyurea, the incidence of stroke has decreased.

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