Background: Platelet function is driven by the expression of specialized surface markers. The concept of distinct circulating subpopulations of platelets has emerged in recent years, but their exact nature remains debatable.
Objectives: To design a spectral flow cytometry-based phenotyping workflow to provide a more comprehensive characterization, at a global and individual level, of surface markers in resting and activated healthy platelets, and to apply this workflow to investigate how responses differ according to platelet age.
Background: Assessment of platelet function is key in diagnosing bleeding disorders and evaluating antiplatelet drug efficacy. However, there is a prevailing "one-size-fits-all" approach in the interpretation of measures of platelet reactivity, with arbitrary cutoffs often derived from healthy volunteer responses.
Objectives: Our aim was to compare well-used platelet reactivity assays.
Background: Major trauma results in dramatic changes in platelet behavior. Newly formed platelets are more reactive than older platelets, but their contributions to hemostasis and thrombosis after severe injury have not been previously evaluated.
Objectives: To determine how immature platelet metrics and plasma thrombopoietin relate to clinical outcomes after major injury.
Research into the natural aging process of platelets has garnered much research interest in recent years, and there have long been associations drawn between the proportion of newly formed platelets in the circulation and the risk of thrombosis. However, these observations have largely been demonstrated in patient groups in which there may be underlying systemic changes that effect platelet function. Recent advances in technology have allowed in-depth analysis of differently aged platelets isolated from the peripheral blood of healthy individuals and have demonstrated that aged platelets, often referred to as senescent platelets, undergo extensive changes in the transcriptome and proteome.
View Article and Find Full Text PDFPlatelet ageing is an area of research which has gained much interest in recent years. Newly formed platelets, often referred to as reticulated platelets, young platelets or immature platelets, are defined as RNA-enriched and have long been thought to be hyper-reactive. This latter view is largely rooted in associations and observations in patient groups with shortened platelet half-lives who often present with increased proportions of newly formed platelets.
View Article and Find Full Text PDFThe proportion of young platelets, also known as newly formed or reticulated, within the overall platelet population has been clinically correlated with adverse cardiovascular outcomes. However, our understanding of this is incomplete because of limitations in the technical approaches available to study platelets of different ages. In this study, we have developed and validated an in vivo temporal labeling approach using injectable fluorescent antiplatelet antibodies to subdivide platelets by age and assess differences in functional and molecular characteristics.
View Article and Find Full Text PDFBackground: Platelets circulate in the blood of healthy individuals for approximately 7-10 days regulated by finely balanced processes of production and destruction. As platelets are anucleate we reasoned that their protein composition would change as they age and that this change would be linked to alterations in structure and function.
Objective: To isolate platelets of different ages from healthy individuals to test the hypothesis that changes in protein content cause alterations in platelet structure and function.
We have identified a rare missense variant on chromosome 9, position 125145990 (GRCh37), in exon 8 in PTGS1 (the gene encoding cyclo-oxygenase 1, COX-1, the target of anti-thrombotic aspirin therapy). We report that in the homozygous state within a large consanguineous family this variant is associated with a bleeding phenotype and alterations in platelet reactivity and eicosanoid production. Western blotting and confocal imaging demonstrated that COX-1 was absent in the platelets of three family members homozygous for the PTGS1 variant but present in their leukocytes.
View Article and Find Full Text PDFTrauma hemorrhage is a leading cause of death and disability worldwide. Platelets are fundamental to primary hemostasis, but become profoundly dysfunctional in critically injured patients by an unknown mechanism, contributing to an acute coagulopathy which exacerbates bleeding and increases mortality. The objective of this study was to elucidate the mechanism of platelet dysfunction in critically injured patients.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
August 2017
Objectives: The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists. This, however, seems contradictory with the platelet hyper-reactivity that is associated with several pathological conditions that are associated with increased circulating levels of molecules that are LXR and FXR ligands, such as hyperlipidemia, type 2 diabetes mellitus, and obesity.
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