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High-Dimensional Single-Cell Mass Cytometry Demonstrates Differential Platelet Functional Phenotypes in Infants With Congenital Heart Disease.
Gu, Sean X; Marcus, Brian S; Gu, Vivian W; Varghese, Adarsh P; Hwa, John; Faustino, E Vincent S.
Afiliación
  • Gu SX; Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT. (S.X.G.).
  • Marcus BS; Department of Pediatrics, Yale University School of Medicine, New Haven, CT. (B.S.M., E.V.S.F.).
  • Gu VW; Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT. (V.W.G., A.P.V., J.H.).
  • Varghese AP; Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT. (V.W.G., A.P.V., J.H.).
  • Hwa J; Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT. (V.W.G., A.P.V., J.H.).
  • Faustino EVS; Department of Pediatrics, Yale University School of Medicine, New Haven, CT. (B.S.M., E.V.S.F.).
Arterioscler Thromb Vasc Biol ; 2024 Aug 22.
Article en En | MEDLINE | ID: mdl-39171400
ABSTRACT

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, 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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos