@article{8c24b7b7d4cb4c3bae35a933f1d34524,
title = "Assessment of neonatal, cord, and adult platelet granule trafficking and secretion",
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.",
keywords = "Hemostasis, neonatal hematology, platelet, protease-activated receptors",
author = "Ngo, {Anh T.P.} and Jawaad Sheriff and Rocheleau, {Anne D.} and Matthew Bucher and Jones, {Kendra R.} and Sepp, {Anna Liisa I.} and Malone, {Lisa E.} and Amanda Zigomalas and Alina Maloyan and Bahou, {Wadie F.} and Danny Bluestein and McCarty, {Owen J.T.} and Haley, {Kristina M.}",
note = "Funding Information: This work was supported by the National Heart, Lung, and Blood Institute: [grant numbers R01 HL119096-03, U01 HL131052-02, and R01HL101972]. The authors thank Dr. Cecilia Avila, Department of Obstetrics and Gynecology, Stony Brook University Hospital and Bailey Simon, Knight Cardiovascular Institute, Oregon Health and Science University for providing cord blood samples. We thank Michael Recht, Stewart Worthington and Alysia Cox, The Hemophilia Center, Oregon Health and Science University for providing neonatal peripheral heel-stick samples. They also thank Marisa L.D. Thierheimer, Department of Chemical Engineering, Oregon State University and Brianne Polehinke, Stony Brook University, for their assistance with the experiments. This work was supported by program income funds generated by participation in HRSA Award no. H30MC24049, and by grants from the National Institutes of Health (R01HL101972 to O.M., U01 HL131052-02 to D.B., and R01 HL119096-03 to W.F.B.). Funding Information: The authors thank Dr. Cecilia Avila, Department of Obstetrics and Gynecology, Stony Brook University Hospital and Bailey Simon, Knight Cardiovascular Institute, Oregon Health and Science University for providing cord blood samples. We thank Michael Recht, Stewart Worthington and Alysia Cox, The Hemophilia Center, Oregon Health and Science University for providing neonatal peripheral heel-stick samples. They also thank Marisa L.D. Thierheimer, Department of Chemical Engineering, Oregon State University and Brianne Polehinke, Stony Brook University, for their assistance with the experiments. This work was supported by program income funds generated by participation in HRSA Award no. H30MC24049, and by grants from the National Institutes of Health (R01HL101972 to O.M., U01 HL131052-02 to D.B., and R01 HL119096-03 to W.F.B.). Funding Information: This work was supported by the National Heart, Lung, and Blood Institute: [grant numbers R01 HL119096-03, U01 HL131052-02, and R01HL101972]. Publisher Copyright: {\textcopyright} 2019, {\textcopyright} 2019 Taylor & Francis Group, LLC.",
year = "2020",
month = jan,
day = "2",
doi = "10.1080/09537104.2019.1573314",
language = "English (US)",
volume = "31",
pages = "68--78",
journal = "Platelets",
issn = "0953-7104",
publisher = "Informa Healthcare",
number = "1",
}