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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society of Hematology
2023
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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 |
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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 Blood was withdrawn at up to 3 different time points in neonates (t(1): 0-2, t(2): 3-7, and t(3): 8-14 days after birth).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 |
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