The evolving knowledge on primary hemostasis in neonates

Neonatologists spend considerable effort with the aim of preventing neonatal bleeding. Traditionally, platelet failure has been widely considered a crucial determinant of neonatal hemorrhage. However, recent research challenges this view and suggests that platelet hyporeactivity may be part of a carefully balanced hemostatic system. This review explores the broader process of primary hemostasis in both term and preterm infants, beyond platelet function alone, integrating evidence from in-vitro, laboratory and point-of-care studies. Overall, studies raise concerns about the possible contribution of platelet dysfunction to an increased bleeding risk, especially in preterm infants. The clinical relevance of these findings remains uncertain, owing to methodological heterogeneity and the limited correlation with meaningful outcomes. Although platelet hyporeactivity has been largely attributed to a developmental impairment, it might also depend on prevailing up-regulated inhibitory pathways. Nevertheless, functional differences in plasma proteins provide enhanced adhesive capacities, supporting platelet-subendothelium interaction, further facilitated by higher hematocrit levels. Molecular explanations for platelet singularities are being uncovered thanks to omics studies. Advanced technologies such as microfluidics are enabling the study of cross-talking endothelium and platelets. Yet, the details of the interactions between platelets, erythrocytes, and white blood cells remain to be elucidated in the setting of developmental hemostasis. Emerging evidence on distinct pathways driving a lower pro-inflammatory tendency of the neonatal milieu might explain the poorer outcomes of those preterm infants receiving multiple transfusions of adult blood products. Awareness of the unique equilibrium of neonatal primary hemostasis calls for further research into the impact of neonatal therapies on hemostatic balance.