Plasma Proteomic Analysis Reveals Age-Specific Changes in Platelet- and Endothelial Cell-Derived Proteins and Regulators of Plasma Coagulation and Fibrinolysis.

This post hoc study of a plasma proteomic database investigated hemostatic proteins in the context of developmental hemostasis. Twenty-seven hemostatic proteins changed expression with age, and the hemostatic profile of neonates was unique. Appreciating developmental hemostasis through proteomics may lead to more personalized medicine for hospitalized children.

Age-specific differences in the in vitro anticoagulant effect of Bivalirudin in healthy neonates and children compared to adults.

Bivalirudin is a reversible direct thrombin inhibitor that inhibits both bound and free thrombin and binds to the active (catalytic) and fibrinogen-binding sites of thrombin, with high affinity and specificity. Off-label use of bivalirudin in the paediatric population has increased, as an alternative to heparin, particularly in the setting of anticoagulation for patients undergoing coronary bypass surgery (CPB), extracorporeal life support (ECLS) and those on ventricular assist devices (VAD). This study aimed to determine the age-specific in vitro effect of bivalirudin in children compared to adults. Age-specific pools (neonates, ≤2 years, >2 to 5 years, 6 to 10 years, 11 to 17 years and Adults) were prepared using platelet poor plasma samples from 20 individuals per age group. Pooled plasma was spiked with increasing concentrations of Bivalirudin (from 0 g/mL to 10µg/mL), and thrombin inhibition was measured using standard coagulation assays. There was a significantly increased response to bivalirudin across all paediatric age groups as compared to adults. The age-specific difference in response to bivalirudin was specifically evident in neonates, where the potential to generate thrombin was decreased 2-fold compared to adults (p < 0.001). Our findings support the concept of age-specific pharmaco-dynamic responses to Bivalirudin and support the need for further ex vivo studies in hospitalised children to determine accurate clinical dosing recommendations.

Guidelines for panel design, optimization, and performance of whole blood multi-color flow cytometry of platelet surface markers.

Flow cytometry is a valuable tool in determining the phenotype and function of platelets accurately. The emergence of platelet flow cytometry in recent years provides an attractive alternative to other platelet analytical techniques, with advantages such as requiring small volumes and being highly sensitive to minimal changes in receptor function and expression. Here we present a methodical approach encompassing the stages in the development and optimization of platelet flow cytometry panels based on our extensive experience in this area.