Prostaglandin E₂ levels and platelet function are different in cord blood compared to adults

Summary

Neonatal platelets support primary haemostasis and thrombin generation as well as adult platelets, despite observable hypoaggregability in vitro. High prostaglandin E₂ levels at accouchement could account for inhibited platelet function via the EP4 receptor. We set out to determine prostaglandin E₂ plasma levels in cord blood of healthy neonates and evaluate the impact of prostaglandin E₂ on platelet function in adult and cord blood samples. Prostaglandin E₂ plasma levels were measured in cord blood and venous adult blood using GC-MS. Impact of prostaglandin E₂ on platelet aggregation was measured by spiking cord blood and adult samples. Contributions of EP₃ and EP₄ receptors were evaluated using respective antagonists. Intracellular cAMP concentrations were measured using a commercial ELISA-kit. Prosta-glandin E₂ plasma levels were substantially higher in cord blood than in adult samples. Spiking with prostaglandin E₂ resulted in a slight but consistent reduction of platelet aggregation in adult blood, but response to PGE₂ was blunted in cord blood samples. Aggregation response of spiked adult samples was still higher than with non-spiked cord blood samples. Blockage of EP4 receptors resulted in improved platelet aggregation in adult platelets upon prostaglandin E₂ spiking, while aggregation in cord blood samples remained unaltered. Intracellular cAMP concentrations after preincubation with prostaglandin E₂ were only increased in adult samples. In conclusion, very high prosta -glandin E₂ concentrations in cord blood affect platelet function. This effect may partially explain neonatal platelet hypoaggregability. Peak levels of prostaglandin E₂ can potentially protect against birth stressinduced platelet activation.

Keywords

Cyclic AMP - neonate - prostaglandin E₂ - prostanoid receptor EP4 - platelet aggregation

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