Cargando…

Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study

Erythrocytes undergo a well-defined switch from fetal to postnatal circulation, which is mainly reflected by the stage-specific expression of hemoglobin chains. Perinatal alterations in thrombopoiesis are poorly understood. We assessed the ontogenesis of platelet phenotype and function from early pr...

Descripción completa

Detalles Bibliográficos
Autores principales: Weiss, Lukas J., Drayss, Maria, Mott, Kristina, Beck, Sarah, Unsin, David, Just, Bastian, Speer, Christian P., Härtel, Christoph, Andres, Oliver, Schulze, Harald
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Hematology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432615/
https://www.ncbi.nlm.nih.gov/pubmed/37042931
http://dx.doi.org/10.1182/bloodadvances.2023009824
_version_ 1785091461514002432
author Weiss, Lukas J.
Drayss, Maria
Mott, Kristina
Beck, Sarah
Unsin, David
Just, Bastian
Speer, Christian P.
Härtel, Christoph
Andres, Oliver
Schulze, Harald
author_facet Weiss, Lukas J.
Drayss, Maria
Mott, Kristina
Beck, Sarah
Unsin, David
Just, Bastian
Speer, Christian P.
Härtel, Christoph
Andres, Oliver
Schulze, Harald
author_sort Weiss, Lukas J.
collection PubMed
description Erythrocytes undergo a well-defined switch from fetal to postnatal circulation, which is mainly reflected by the stage-specific expression of hemoglobin chains. Perinatal alterations in thrombopoiesis are poorly understood. We assessed the ontogenesis of platelet phenotype and function from early prematurity to adulthood. We recruited 64 subjects comprising 7 extremely preterm (27-31 weeks gestational age), 25 moderately preterm (32-36 weeks), 10 term neonates, 8 infants (<2 years), 5 children (2-13 years), and 9 adults (>13 years). Blood was withdrawn at up to 3 different time points in neonates (t(1): 0-2, t(2): 3-7, and t(3): 8-14 days after birth). We found that the expression levels of the major surface receptors for fibrinogen, collagen, vWF, fibronectin, and laminin were reduced but correlated with decreased platelet size, indicating a normal surface density. Although CD62P and CD63 surface exposure upon stimulation with TRAP-6, ADP, or U46619 was unaltered or only slightly reduced in neonates, GPIIb/IIIa inside-out and outside-in activation was blunted but showed a continuous increase until adulthood, correlating with the expression of the GPIIb/IIIa regulating tetraspanin CD151. Platelet subpopulation analysis using automated clustering revealed that neonates presented with a CD63(+)/PAC-1(–) pattern, followed by a continuous increase in CD63(+)/PAC-1(+) platelets until adulthood. Our findings revealed that the number of platelet-monocyte and platelet-neutrophil aggregates, but not platelet-lymphocyte aggregates, is increased in neonates and that neonatal aggregate formation depends in part on CD62P activation. Our PLatelets In Neonatal Infants Study (PLINIUS) provides several lines of evidence that the platelet phenotype and function evolve continuously from neonates to adulthood.
format Online
Article
Text
id pubmed-10432615
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher The American Society of Hematology
record_format MEDLINE/PubMed
spelling pubmed-104326152023-08-18 Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study Weiss, Lukas J. Drayss, Maria Mott, Kristina Beck, Sarah Unsin, David Just, Bastian Speer, Christian P. Härtel, Christoph Andres, Oliver Schulze, Harald Blood Adv Platelets and Thrombopoiesis Erythrocytes undergo a well-defined switch from fetal to postnatal circulation, which is mainly reflected by the stage-specific expression of hemoglobin chains. Perinatal alterations in thrombopoiesis are poorly understood. We assessed the ontogenesis of platelet phenotype and function from early prematurity to adulthood. We recruited 64 subjects comprising 7 extremely preterm (27-31 weeks gestational age), 25 moderately preterm (32-36 weeks), 10 term neonates, 8 infants (<2 years), 5 children (2-13 years), and 9 adults (>13 years). Blood was withdrawn at up to 3 different time points in neonates (t(1): 0-2, t(2): 3-7, and t(3): 8-14 days after birth). We found that the expression levels of the major surface receptors for fibrinogen, collagen, vWF, fibronectin, and laminin were reduced but correlated with decreased platelet size, indicating a normal surface density. Although CD62P and CD63 surface exposure upon stimulation with TRAP-6, ADP, or U46619 was unaltered or only slightly reduced in neonates, GPIIb/IIIa inside-out and outside-in activation was blunted but showed a continuous increase until adulthood, correlating with the expression of the GPIIb/IIIa regulating tetraspanin CD151. Platelet subpopulation analysis using automated clustering revealed that neonates presented with a CD63(+)/PAC-1(–) pattern, followed by a continuous increase in CD63(+)/PAC-1(+) platelets until adulthood. Our findings revealed that the number of platelet-monocyte and platelet-neutrophil aggregates, but not platelet-lymphocyte aggregates, is increased in neonates and that neonatal aggregate formation depends in part on CD62P activation. Our PLatelets In Neonatal Infants Study (PLINIUS) provides several lines of evidence that the platelet phenotype and function evolve continuously from neonates to adulthood. The American Society of Hematology 2023-04-13 /pmc/articles/PMC10432615/ /pubmed/37042931 http://dx.doi.org/10.1182/bloodadvances.2023009824 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Platelets and Thrombopoiesis
Weiss, Lukas J.
Drayss, Maria
Mott, Kristina
Beck, Sarah
Unsin, David
Just, Bastian
Speer, Christian P.
Härtel, Christoph
Andres, Oliver
Schulze, Harald
Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study
title Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study
title_full Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study
title_fullStr Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study
title_full_unstemmed Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study
title_short Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study
title_sort ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: the plinius study
topic Platelets and Thrombopoiesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432615/
https://www.ncbi.nlm.nih.gov/pubmed/37042931
http://dx.doi.org/10.1182/bloodadvances.2023009824
work_keys_str_mv AT weisslukasj ontogenesisoffunctionalplateletsubpopulationsfrompretermandtermneonatestoadulthoodthepliniusstudy
AT drayssmaria ontogenesisoffunctionalplateletsubpopulationsfrompretermandtermneonatestoadulthoodthepliniusstudy
AT mottkristina ontogenesisoffunctionalplateletsubpopulationsfrompretermandtermneonatestoadulthoodthepliniusstudy
AT becksarah ontogenesisoffunctionalplateletsubpopulationsfrompretermandtermneonatestoadulthoodthepliniusstudy
AT unsindavid ontogenesisoffunctionalplateletsubpopulationsfrompretermandtermneonatestoadulthoodthepliniusstudy
AT justbastian ontogenesisoffunctionalplateletsubpopulationsfrompretermandtermneonatestoadulthoodthepliniusstudy
AT speerchristianp ontogenesisoffunctionalplateletsubpopulationsfrompretermandtermneonatestoadulthoodthepliniusstudy
AT hartelchristoph ontogenesisoffunctionalplateletsubpopulationsfrompretermandtermneonatestoadulthoodthepliniusstudy
AT andresoliver ontogenesisoffunctionalplateletsubpopulationsfrompretermandtermneonatestoadulthoodthepliniusstudy
AT schulzeharald ontogenesisoffunctionalplateletsubpopulationsfrompretermandtermneonatestoadulthoodthepliniusstudy