Neonatal platelets: mediators of primary hemostasis in the developing hemostatic system

Abstract

The human hemostatic system is developmentally regulated, resulting in qualitative and quantitative differences in the mediators of primary and secondary hemostasis as well as fibrinolysis in neonates and infants. Although gestational age-related differences in coagulation factor levels occur, the existence of a unique neonatal platelet phenotype remains controversial. Complicated by difficulties in obtaining adequate neonatal blood volumes with which to perform functional assays, ambiguity surrounds the characterization of neonatal platelets. Thus, much of the current knowledge of neonatal platelet function has been based on studies from cord blood samples. Studies suggest that cord blood-derived platelets, as a surrogate for neonatal platelets, are hypofunctional when compared with adult platelets. This relative platelet dysfunction, combined with a propensity toward thrombocytopenia in the neonatal intensive care unit population, creates a clinical conundrum regarding the appropriate administration of platelet transfusions. This review provides an appraisal of the distinct functional phenotype of neonatal platelets. Neonatal platelet transfusion practices and the impact of the relatively hypofunctional neonatal platelet on those practices will be considered.

Figure 1

The mechanisms of platelet adhesion, activation and secretion. The platelet receptor complex GPIb/V/IX mediates platelet recruitment to VWF bound to exposed extracellular matrix proteins, such as collagen. Subsequent platelet activation results in an increase in an increase in intracellular calcium (1), increased phosphatidylserine exposure to create a negatively charged surface (2), alpha and dense granule release (3), conversion of the GPIIb/IIIa receptor to a high affinity state (4), thromboxane A₂ generation (5), and cytoskeletal rearrangement (6).

Figure 2

The Assessment of Platelet Interactions (hAPI) assay is being developed in order to characterize the functional phenotype of neonatal platelets obtained directly from the neonate. A representative neonatal sample is depicted here. Anti-coagulated whole blood obtained from a newborn via heelstick was layered over glass slides coated with collagen or fibrinogen. The degree of platelet adhesion and spreading was monitored by differential interference contrast microscopy (Nomarski microscopy). P-selectin expression was determined through the binding of a FITC-conjugated anti-P-selectin antibody (P-selectin), allowing for the assessment of P-selectin positive platelets (merge). Images are at 63×; scale bar = 10 μm.