Platelets in the neonate: Not just a small adult

Abstract

Neonates, particularly those born preterm, have a high incidence of thrombocytopenia and bleeding, most commonly in the brain. Because of this, it has historically been accepted that neonates should be transfused at higher platelet counts than older children or adults, to decrease their bleeding risk. However, a number of observational studies and a recent large, randomized trial found a higher incidence of bleeding and mortality in neonates who received more platelet transfusions. The mechanisms underlying the deleterious effects of platelet transfusions in neonates are unknown, but it has been hypothesized that transfusing adult platelets into the very different physiological environment of a neonate may result in a "developmental mismatch" with potential negative consequences. Specifically, neonatal platelets are hyporeactive in response to multiple agonists and upon activation express less surface P-selectin than adult platelets. However, this hyporeactivity is well balanced by factors in neonatal blood that promote clotting, such as the elevated hematocrit, elevated von Willebrand factor (VWF) levels, and a predominance of ultra-long VWF polymers, with the net result of normal neonatal primary hemostasis. So far, most studies on the developmental differences between neonatal and adult platelets have focused on their hemostatic functions. However, it is now clear that platelets have important nonhemostatic functions, particularly in angiogenesis, immune responses, and inflammation. Whether equally important developmental differences exist with regard to those nonhemostatic platelet functions and how platelet transfusions perturb those processes in neonates remain unanswered questions.

Keywords: hemostasis; inflammation; neonate; platelet; platelet transfusion.

FIGURE 1

Schematic representation of key developmental differences between neonatal and adult platelets, and potential effects on immune cells. Upon activation, human neonatal platelets express less P‐selectin and release their alpha granule content (including cytokines and chemokines) less effectively than adult platelets. Decreased P‐selectin surface expression results in a reduced ability to interact with and activate immune cells, including neutrophils and monocytes. A neutrophil is shown as an example. The reduced NET formation in neonates is due to the presence of a placenta‐derived NET inhibitor. Abbreviations: NET, neutrophil extracellular trap; PSGL‐1, P‐selectin glycoprotein ligand‐1