OC 39.1 - Phenotypic switch of platelet function from preterm to term neonates – daily life data from the Platelets In Neonatal Infants Study (PLINIUS)

Background: Prematurity is a major risk factor for neonatal hemorrhage, sepsis, and thrombosis. Platelet receptor function in premature infants and its transformation from fetal to postnatal reactivity is yet incompletely understood.

Aims: Platelet receptor expression and reactivity to agonists were studied in premature and term infants and correlated with their respective gestational age (GA).

Methods: We recruited a cohort of 68 subjects comprising seven early preterm (27-31 weeks GA), 26 preterm (32–36 weeks GA) and 13 term neonates. Eight Infants ( < 2 years), five children (2–12 years) and nine adolescents/adults (>12 years) served as controls. After informed consent, blood was drawn at three different time points (days 0–2, 3–7, and 8–14 respectively) and analyzed by flow cytometry. The study was approved by the local ethics committee.

Results: Expression levels of the major surface receptors for fibrinogen (CD41/CD61), collagen (GPVI; CD29/CD49b), von-Willebrand factor (CD42a/CD42b), and TLR-4 were overall reduced, but showed a strong linear correlation with decreased platelet size (forward scatter), indicating an unaltered surface density. P-selectin (CD62P) surface neo-exposition (figure 1A) upon stimulation with ADP or GPVI-activating antibody HY101 increased significantly with rising GA, whereas reactivity towards TRAP-6 stimulation was unaltered (figure 1B). Unexpectedly, integrin activation (PAC-1 binding, figure 2) upon ADP or TRAP-6 was blunted in neonates and infants. In contrast, the proportion of platelet-leukocyte (CD45+/CD41+) and platelet-monocyte aggregates (CD14+/CD41+) were significantly increased in preterm and term neonates without clinical signs of infection (mean 41% vs. 20%, p< 0.001, and 7% vs. 5%, p< 0.05, respectively).

Conclusion(s): Our findings imply that platelet signaling maturation from fetal to neonatal platelet function is uncoupled and is not directly associated with receptor surface expression. Development of alpha granule release precedes GPIIb/IIIa integrin activation, an observation which might be exploited to better understand this phenotypic switch. Our data suggest an immune modulatory role of neonatal platelets beyond hemostasis.