ArticleThrombosis and haemostasis2018
Significant Hypo-Responsiveness to GPVI and CLEC-2 Agonists in Pre-Term and Full-Term Neonatal Platelets and following Immune Thrombocytopenia.
Article in Thrombosis and haemostasis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Optimizing platelet transfusion thresholds in preterm infants: a systematic review and narrative synthesis of impacts on survival and neurodevelopment.Blood transfusion = Trasfusione del sanguePooled it
- Analysis of plasma exosomal differential proteins and bioinformatics in intrahepatic cholestasis of pregnancy.Frontiers in global women's health · 2026Article
- Enhanced regenerative and developmental potential of embryonal and stem cell-derived platelets compared to adult platelets.Cell reports. Medicine · 2025Article
- Demographic diversity in platelet function and response to antiplatelet therapy.Trends in pharmacological sciences · 2025Review
- Quantitative label-free mass spectrometry reveals content and signaling differences between neonatal and adult platelets.Journal of thrombosis and haemostasis : JTH · 2024Article
- Composition of thrombi in zebrafish: similarities and distinctions with mammals.Journal of thrombosis and haemostasis : JTH · 2024Article
- The Hemostatic System in Newborns and the Risk of Neonatal Thrombosis.International journal of molecular sciences · 2023Review
- Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study.Blood advances · 2023Article
- Platelet transfusions in a murine model of neonatal polymicrobial sepsis: Divergent effects on inflammation and mortality.Transfusion · 2022Article
- Fruitflow inhibits platelet function by suppressing Akt/GSK3β, Syk/PLCγ2 and p38 MAPK phosphorylation in collagen-stimulated platelets.BMC complementary medicine and therapies · 2022Article
- Platelets in the neonate: Not just a small adult.Research and practice in thrombosis and haemostasis · 2022Article
- Neonatal platelet physiology and implications for transfusion.Platelets · 2022Review
- Platelets in pediatric and neonatal sepsis: novel mediators of the inflammatory cascade.Pediatric research · 2022Review
- Curcumin-Based Inhibitors of Thrombosis and Cancer Metastasis Promoting Factor CLEC 2 from Traditional Medicinal SpeciesEvidence-based complementary and alternative medicine : eCAM · 2022Article
- Expanding the genetic spectrum of TUBB1-related thrombocytopenia.Blood advances · 2021Article
- Age-Dependent Control of Collagen-Dependent Platelet Responses by Thrombospondin-1-Comparative Analysis of Platelets from Neonates, Children, Adolescents, and Adults.International journal of molecular sciences · 2021Article
- Qualitative and Quantitative Comparison of Plasma Exosomes from Neonates and Adults.International journal of molecular sciences · 2021Article
- Hemostatic Challenges in Neonates.Frontiers in pediatrics · 2021Review
- The Role of CLEC-2 and Its Ligands in Thromboinflammation.Frontiers in immunology · 2021Review
- Morphometric image analysis of placental C-type lectin domain family 2, member D (CLEC2D) immuno-expression in HIV associated pre-eclampsia.European journal of obstetrics & gynecology and reproductive biology: X · 2019Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 4 countries.
Funding
Abstract
Neonatal platelets are hypo-reactive to the tyrosine kinase-linked receptor agonist collagen. Here, we have investigated whether the hypo-responsiveness is related to altered levels of glycoprotein VI (GPVI) and integrin α2β1, or to defects in downstream signalling events by comparison to platelet activation by C-type lectin-like receptor 2 (CLEC-2). GPVI and CLEC-2 activate a Src- and Syk-dependent signalling pathway upstream of phospholipase C (PLC) γ2. Phosphorylation of a conserved YxxL sequence known as a (hemi) immunotyrosine-based-activation-motif (ITAM) in both receptors is critical for Syk activation. Platelets from human pre-term and full-term neonates display mildly reduced expression of GPVI and CLEC-2, as well as integrin αIIbβ3, accounted for at the transcriptional level. They are also hypo-responsive to the two ITAM receptors, as shown by measurement of integrin αIIbβ3 activation, P-selectin expression and Syk and PLCγ2 phosphorylation. Mouse platelets are also hypo-responsive to GPVI and CLEC-2 from late gestation to 2 weeks of age, as determined by measurement of integrin αIIbβ3 activation. In contrast, the response to G protein-coupled receptor agonists was only mildly reduced and in some cases not altered in neonatal platelets of both species. A reduction in response to GPVI and CLEC-2, but not protease-activated receptor 4 (PAR-4) peptide, was also observed in adult mouse platelets following immune thrombocytopenia, whereas receptor expression was not impaired. Our results demonstrate developmental differences in platelet responsiveness to GPVI and CLEC-2, and also following immune platelet depletion leading to reduced Syk activation. The rapid generation of platelets during development or following platelet depletion is achieved at the expense of signalling by ITAM-coupled receptors.
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Registered trials
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