SUMMARY
Background
Acquired and inherited bleeding disorders may present in the neonatal period with devastating lifelong effects. Diagnosing bleeding disorders in the neonatal population could aid in preventing and treating the associated complications. However, currently available platelet function testing is limited in neonates owing to difficulties obtaining adequate blood volume, lack of normal reference ranges, and an incomplete understanding of the neonatal platelet functional phenotype.
Objective
Develop small-volume, whole blood platelet function assays to quantify and compare neonatal and adult platelet function.
Methods and Results
Peripheral blood was obtained from healthy, full-term neonates at 24-hours of life. Platelet activation, secretion, and aggregation were measured via flow cytometry. Platelet adhesion and aggregation were assessed under static and flow conditions. As compared to adult platelets, peripheral neonatal platelet P-selectin expression and integrin glycoprotein (GP) IIbIIIa activation was significantly reduced in response to the G protein-coupled receptor (GPCR)-agonists thrombin receptor activator peptide-6 (TRAP-6), adenosine 5′-diphosphate (ADP), and U46619 and the immunoreceptor tyrosine-based activation motif (ITAM)-signaling pathway agonists collagen-related peptide (CRP) and rhodocytin. Neonatal platelet aggregation was markedly reduced in response to TRAP-6, ADP, U46619, CRP, and rhodocytin compared to adult platelets. The extent of neonatal and adult platelet adhesion and aggregate formation under static and shear conditions on collagen and von Willebrand factor (VWF) were similar.
Conclusions
As compared to adult platelets, we found neonatal platelet activation and secretion were blunted in response to GPCR- or ITAM-agonists, while the extent of neonatal platelet adhesion and aggregate formation was similar to adult platelets.