Apollonsky Nataly, Lerner Norma B, Zhang Fengqing, Raybagkar Deepti, Eng Jennifer, Tarazi Reem
Section of Hematology, St. Christopher's Hospital for Children, Philadelphia, PA, USA.
Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute/NIH, Bethesda, Maryland, USA.
Adv Hematol. 2020 Feb 26;2020:8181425. doi: 10.1155/2020/8181425. eCollection 2020.
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. . 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.
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.
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.
本初步研究旨在描述脑血管病变的假定标志物，并在一组神经功能正常的镰状细胞病（SCD）儿童样本中，研究这些标志物、人口统计学因素与认知功能之间的关系。纳入了38名年龄在4至11岁的纯合子HbS儿童。获取了估计智商、凝血和内皮激活标志物、溶血和炎症标志物、经颅多普勒速度、羟基脲使用情况以及人口统计学信息。
通过多元回归分析，生物标志物或血流速度与估计智商之间几乎没有显著的独立关联。乳酸脱氢酶（LDH）独立预测认知功能，但血流速度并未介导这种关系。母亲教育程度、患者年龄和羟基脲使用情况是认知的独立预测因素。鉴于样本量较小，采用套索（LASSO）统计模型进一步确定智商的潜在预测因素，该模型确定LDH、绝对中性粒细胞计数（ANC）、血小板计数、凝血酶 - 抗凝血酶复合物（TAT）、组织因子（TF）、母亲教育程度、年龄和羟基脲为认知的潜在预测因素。
除了年龄和母亲教育程度的影响外，一些血管病变标志物与SCD幼儿的认知功能相关，并且这些关系似乎并非通过血流速度介导。尽管某些变量之间缺乏预期的关联，但研究结果为进一步研究血管病变标志物对无中风的SCD儿童认知功能的影响提供了支持，特别是血管内溶血和凝血/内皮激活，以及羟基脲治疗在预防或逆转认知衰退方面可能发挥的作用。
