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.

Transfusion of Adult, but Not Neonatal, Platelets Promotes Monocyte Trafficking in Neonatal Mice

“…If platelets are properly considered part of the immune cell family, this makes sense, because the early postnatal period is a time when immune development and immune tolerance must be properly balanced. Neonatal platelets have decreased aggregation in response to most agonists, but neonates have normal primary hemostasis, 20 further indicating that the developmental program of neonatal platelets is skewed toward being less inflammatory but with normal functional hemostasis. Further study and model development are needed to understand the physiology of delayed platelet immune development and the implications of its disruption.…”

Immunologic effects of red blood cell and platelet transfusions in neonates

“…When transfusing platelets into neonates, it is important to consider the substantial biological differences that exist between neonates and adults in regard to every organ system, including platelet function [41]. Human neonatal platelets are hyporeactive in response to most agonists and exhibit a degranulation defect and less P-selectin expression upon activation compared to adult platelets [42,43].…”

EBNEO commentary: Platelet transfusions in neonates and brain development: The new frontier

“…Platelets are critical regulators of immune and inflammatory responses, and it has been hypothesised that adult (transfused) platelets are more pro-inflammatory than neonatal platelets. [5][6][7][8] In support of this hypothesis, pre-clinical studies suggest platelet transfusions trigger inflammation or dysregulated immune responses in neonates, in a context-dependent manner. 9 Whether NDI results from the direct effects of transfused platelets on the developing brain or is mediated by higher rates of IVH and BPD observed in infants randomised to the high threshold group EBNEO commentaries on manuscripts relevant to evidence-based neonatal practice are welcomed and published after a formal peer-review process.…”

“…The mechanisms underlying increased morbidity and mortality associated with platelet transfusions are likely related to non‐hemostatic effects of platelets. Platelets are critical regulators of immune and inflammatory responses, and it has been hypothesised that adult (transfused) platelets are more pro‐inflammatory than neonatal platelets 5–8 . In support of this hypothesis, pre‐clinical studies suggest platelet transfusions trigger inflammation or dysregulated immune responses in neonates, in a context‐dependent manner 9 .…”