High-Dimensional Single-Cell Mass Cytometry Demonstrates Differential Platelet Functional Phenotypes in Infants With Congenital Heart Disease

血小板 血小板活化 血管性血友病因子 免疫学 医学 细胞因子 心脏病 全血 表型 内科学 流式细胞术 内分泌学 生物 基因 生物化学
作者
Sean X. Gu,Brian S. Marcus,Vivian W. Gu,Adarsh Varghese,John Hwa,E. Vincent S. Faustino
出处
期刊:Arteriosclerosis, Thrombosis, and Vascular Biology [Ovid Technologies (Wolters Kluwer)]
卷期号:44 (12): 2530-2539 被引量:3
标识
DOI:10.1161/atvbaha.124.321131
摘要

BACKGROUND: Congenital heart disease (CHD) is a group of complex heart defects associated with hematologic abnormalities, including increased risk of thrombotic and bleeding events. Past studies have observed evidence of platelet hyperreactivity, while other studies showed decreased platelet activation in patients with CHD. The goal of this study was to develop a mass spectrometry approach to characterize single platelets in infants with CHD and identify potential etiology for such discrepant results. METHODS: We enrolled 19 infants with CHD along with 21 non-CHD controls at Yale New Haven Children’s Heart Center. A single-cell high-dimensional mass cytometry method was developed to quantitatively interrogate platelet surface markers in whole blood. Additionally, plasma cytokine analysis was performed through a multiplexed panel of 52 vascular and inflammatory markers to assess for platelet releasates. RESULTS: We found that infants with CHD had significant differences in platelet activation and functional markers by mass cytometry compared with non-CHD controls. Based on cell surface markers, we classified the platelets into 8 subpopulations (P0 to P7). Distinct subpopulations of platelets (P1, P4, and P5) exhibiting decreased aggregatory phenotype but altered secretory phenotypes were also identified and found to be more abundant in the blood of infants with CHD. Electron microscopy identified increased proportion of hypogranular platelets in CHD. Moreover, cytokine analysis demonstrated an overall increase in plasma cytokines and biomarkers in CHD, including IL (interleukin)-6, IL-8, IL-27, RANTES (regulated upon activation, normal T cell expressed and secreted), and VWF (von Willebrand factor), which are expressed in platelet granules and can be released upon activation. CONCLUSIONS: We developed a robust mass cytometry approach to identify platelet phenotypic heterogeneity. Infants with CHD had alterations in distinct subpopulations of platelets with overall reduced aggregatory phenotype and secretory dysfunction. These findings suggest that platelets in infants with CHD may be exhausted due to persistent stimulation and may explain both bleeding and thrombotic vascular complications associated with CHD.
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