Assessment of neonatal platelet adhesion, activation, and aggregation

S. M. Baker-Groberg, S. Lattimore, Michael Recht, Owen McCarty, Kristina Haley

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Essentials: Assays are needed to aid in the diagnosis of platelet dysfunction in the neonatal population. We developed small-volume assays to assess neonatal platelet activation and aggregation. Compared to adult platelets, neonatal platelet activation and secretion was reduced. The extent of neonatal and adult platelet adhesion and aggregate formation were similar. Summary: Background: Acquired and inherited bleeding disorders may present in the neonatal period with devastating lifelong effects. Diagnosing bleeding disorders in the neonatal population could aid in preventing and treating the associated complications. However, currently available platelet function testing is limited in neonates, owing to difficulties in obtaining an adequate blood volume, a lack of normal reference ranges, and an incomplete understanding of the neonatal platelet functional phenotype. Objective: To develop small-volume, whole blood platelet function assays in order to quantify and compare neonatal and adult platelet function. Methods and Results: Peripheral blood was obtained from healthy, full-term neonates at 24 h of life. Platelet activation, secretion and aggregation were measured via flow cytometry. Platelet adhesion and aggregation were assessed under static and flow conditions. As compared with adult platelets, peripheral neonatal platelet P-selectin expression and integrin glycoprotein IIbIIIa activation were significantly reduced in response to the G-protein-coupled receptor (GPCR) agonists thrombin receptor activator peptide-6 (TRAP-6), ADP, and U46619, and the immunoreceptor tyrosine-based activation motif (ITAM) signaling pathway agonists collagen-related peptide (CRP) and rhodocytin. Neonatal platelet aggregation was markedly reduced in response to TRAP-6, ADP, U46619, CRP and rhodocytin as compared with adult platelets. The extents of neonatal and adult platelet adhesion and aggregate formation under static and shear conditions on collagen and von Willebrand factor were similar. Conclusions: As compared with adult platelets, we found that neonatal platelet activation and secretion were blunted in response to GPCR or ITAM agonists, whereas the extent of neonatal platelet adhesion and aggregate formation was similar to that of adult platelets.

Original languageEnglish (US)
JournalJournal of Thrombosis and Haemostasis
DOIs
StateAccepted/In press - 2016

Fingerprint

Platelet Activation
Platelet Aggregation
Blood Platelets
Immunoreceptor Tyrosine-Based Activation Motif
Thrombin Receptors
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
G-Protein-Coupled Receptors
Adenosine Diphosphate
Reference Values
Hemorrhage
P-Selectin
von Willebrand Factor
Blood Volume
Integrins
Population
Glycoproteins
Flow Cytometry
Collagen

Keywords

  • Neonate
  • Platelet activation
  • Platelet adhesiveness
  • Platelet aggregation
  • Platelet function tests

ASJC Scopus subject areas

  • Hematology

Cite this

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title = "Assessment of neonatal platelet adhesion, activation, and aggregation",
abstract = "Essentials: Assays are needed to aid in the diagnosis of platelet dysfunction in the neonatal population. We developed small-volume assays to assess neonatal platelet activation and aggregation. Compared to adult platelets, neonatal platelet activation and secretion was reduced. The extent of neonatal and adult platelet adhesion and aggregate formation were similar. Summary: Background: Acquired and inherited bleeding disorders may present in the neonatal period with devastating lifelong effects. Diagnosing bleeding disorders in the neonatal population could aid in preventing and treating the associated complications. However, currently available platelet function testing is limited in neonates, owing to difficulties in obtaining an adequate blood volume, a lack of normal reference ranges, and an incomplete understanding of the neonatal platelet functional phenotype. Objective: To develop small-volume, whole blood platelet function assays in order to quantify and compare neonatal and adult platelet function. Methods and Results: Peripheral blood was obtained from healthy, full-term neonates at 24 h of life. Platelet activation, secretion and aggregation were measured via flow cytometry. Platelet adhesion and aggregation were assessed under static and flow conditions. As compared with adult platelets, peripheral neonatal platelet P-selectin expression and integrin glycoprotein IIbIIIa activation were significantly reduced in response to the G-protein-coupled receptor (GPCR) agonists thrombin receptor activator peptide-6 (TRAP-6), ADP, and U46619, and the immunoreceptor tyrosine-based activation motif (ITAM) signaling pathway agonists collagen-related peptide (CRP) and rhodocytin. Neonatal platelet aggregation was markedly reduced in response to TRAP-6, ADP, U46619, CRP and rhodocytin as compared with adult platelets. The extents of neonatal and adult platelet adhesion and aggregate formation under static and shear conditions on collagen and von Willebrand factor were similar. Conclusions: As compared with adult platelets, we found that neonatal platelet activation and secretion were blunted in response to GPCR or ITAM agonists, whereas the extent of neonatal platelet adhesion and aggregate formation was similar to that of adult platelets.",
keywords = "Neonate, Platelet activation, Platelet adhesiveness, Platelet aggregation, Platelet function tests",
author = "Baker-Groberg, {S. M.} and S. Lattimore and Michael Recht and Owen McCarty and Kristina Haley",
year = "2016",
doi = "10.1111/jth.13270",
language = "English (US)",
journal = "Journal of Thrombosis and Haemostasis",
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T1 - Assessment of neonatal platelet adhesion, activation, and aggregation

AU - Baker-Groberg, S. M.

AU - Lattimore, S.

AU - Recht, Michael

AU - McCarty, Owen

AU - Haley, Kristina

PY - 2016

Y1 - 2016

N2 - Essentials: Assays are needed to aid in the diagnosis of platelet dysfunction in the neonatal population. We developed small-volume assays to assess neonatal platelet activation and aggregation. Compared to adult platelets, neonatal platelet activation and secretion was reduced. The extent of neonatal and adult platelet adhesion and aggregate formation were similar. Summary: Background: Acquired and inherited bleeding disorders may present in the neonatal period with devastating lifelong effects. Diagnosing bleeding disorders in the neonatal population could aid in preventing and treating the associated complications. However, currently available platelet function testing is limited in neonates, owing to difficulties in obtaining an adequate blood volume, a lack of normal reference ranges, and an incomplete understanding of the neonatal platelet functional phenotype. Objective: To develop small-volume, whole blood platelet function assays in order to quantify and compare neonatal and adult platelet function. Methods and Results: Peripheral blood was obtained from healthy, full-term neonates at 24 h of life. Platelet activation, secretion and aggregation were measured via flow cytometry. Platelet adhesion and aggregation were assessed under static and flow conditions. As compared with adult platelets, peripheral neonatal platelet P-selectin expression and integrin glycoprotein IIbIIIa activation were significantly reduced in response to the G-protein-coupled receptor (GPCR) agonists thrombin receptor activator peptide-6 (TRAP-6), ADP, and U46619, and the immunoreceptor tyrosine-based activation motif (ITAM) signaling pathway agonists collagen-related peptide (CRP) and rhodocytin. Neonatal platelet aggregation was markedly reduced in response to TRAP-6, ADP, U46619, CRP and rhodocytin as compared with adult platelets. The extents of neonatal and adult platelet adhesion and aggregate formation under static and shear conditions on collagen and von Willebrand factor were similar. Conclusions: As compared with adult platelets, we found that neonatal platelet activation and secretion were blunted in response to GPCR or ITAM agonists, whereas the extent of neonatal platelet adhesion and aggregate formation was similar to that of adult platelets.

AB - Essentials: Assays are needed to aid in the diagnosis of platelet dysfunction in the neonatal population. We developed small-volume assays to assess neonatal platelet activation and aggregation. Compared to adult platelets, neonatal platelet activation and secretion was reduced. The extent of neonatal and adult platelet adhesion and aggregate formation were similar. Summary: Background: Acquired and inherited bleeding disorders may present in the neonatal period with devastating lifelong effects. Diagnosing bleeding disorders in the neonatal population could aid in preventing and treating the associated complications. However, currently available platelet function testing is limited in neonates, owing to difficulties in obtaining an adequate blood volume, a lack of normal reference ranges, and an incomplete understanding of the neonatal platelet functional phenotype. Objective: To develop small-volume, whole blood platelet function assays in order to quantify and compare neonatal and adult platelet function. Methods and Results: Peripheral blood was obtained from healthy, full-term neonates at 24 h of life. Platelet activation, secretion and aggregation were measured via flow cytometry. Platelet adhesion and aggregation were assessed under static and flow conditions. As compared with adult platelets, peripheral neonatal platelet P-selectin expression and integrin glycoprotein IIbIIIa activation were significantly reduced in response to the G-protein-coupled receptor (GPCR) agonists thrombin receptor activator peptide-6 (TRAP-6), ADP, and U46619, and the immunoreceptor tyrosine-based activation motif (ITAM) signaling pathway agonists collagen-related peptide (CRP) and rhodocytin. Neonatal platelet aggregation was markedly reduced in response to TRAP-6, ADP, U46619, CRP and rhodocytin as compared with adult platelets. The extents of neonatal and adult platelet adhesion and aggregate formation under static and shear conditions on collagen and von Willebrand factor were similar. Conclusions: As compared with adult platelets, we found that neonatal platelet activation and secretion were blunted in response to GPCR or ITAM agonists, whereas the extent of neonatal platelet adhesion and aggregate formation was similar to that of adult platelets.

KW - Neonate

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KW - Platelet adhesiveness

KW - Platelet aggregation

KW - Platelet function tests

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