Assessment of neonatal, cord, and adult platelet granule trafficking and secretion

Anh T.P. Ngo, Jawaad Sheriff, Anne D. Rocheleau, Matthew Bucher, Kendra R. Jones, Anna Liisa I. Sepp, Lisa E. Malone, Amanda Zigomalas, Alina Maloyan, Wadie F. Bahou, Danny Bluestein, Owen J.T. McCarty, Kristina M. Haley

Research output: Contribution to journalArticle

Abstract

Despite the transient hyporeactivity of neonatal platelets, full-term neonates do not display a bleeding tendency, suggesting potential compensatory mechanisms which allow for balanced and efficient neonatal hemostasis. This study aimed to utilize small-volume, whole blood platelet functional assays to assess the neonatal platelet response downstream of the hemostatic platelet agonists thrombin and adenosine diphosphate (ADP). Thrombin activates platelets via the protease-activated receptors (PARs) 1 and 4, whereas ADP signals via the receptors P2Y1 and P2Y12 as a positive feedback mediator of platelet activation. We observed that neonatal and cord blood-derived platelets exhibited diminished PAR1-mediated granule secretion and integrin activation relative to adult platelets, correlating to reduced PAR1 expression by neonatal platelets. PAR4-mediated granule secretion was blunted in neonatal platelets, correlating to lower PAR4 expression as compared to adult platelets, while PAR4 mediated GPIIb/IIIa activation was similar between neonatal and adult platelets. Under high shear stress, cord blood-derived platelets yielded similar thrombin generation rates but reduced phosphatidylserine expression as compared to adult platelets. Interestingly, we observed enhanced P2Y1/P2Y12-mediated dense granule trafficking in neonatal platelets relative to adults, although P2Y1/P2Y12 expression in neonatal, cord, and adult platelets were similar, suggesting that neonatal platelets may employ an ADP-mediated positive feedback loop as a potential compensatory mechanism for neonatal platelet hyporeactivity.

Original languageEnglish (US)
Pages (from-to)68-78
Number of pages11
JournalPlatelets
Volume31
Issue number1
DOIs
StatePublished - Jan 2 2020

Keywords

  • Hemostasis
  • neonatal hematology
  • platelet
  • protease-activated receptors

ASJC Scopus subject areas

  • Hematology

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    Ngo, A. T. P., Sheriff, J., Rocheleau, A. D., Bucher, M., Jones, K. R., Sepp, A. L. I., Malone, L. E., Zigomalas, A., Maloyan, A., Bahou, W. F., Bluestein, D., McCarty, O. J. T., & Haley, K. M. (2020). Assessment of neonatal, cord, and adult platelet granule trafficking and secretion. Platelets, 31(1), 68-78. https://doi.org/10.1080/09537104.2019.1573314