title: Prostaglandin E2 levels and platelet function are different in cord blood compared to adults.
abstract: 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. Prostaglandin 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 prostaglandin 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 stress-induced platelet activation.
authors.affiliation: Axel Schlagenhauf, PhD, Department of General Pediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 34/II, A-8036 Graz, Austria, Tel.: +43 316 385 14031, Fax: +43 316 385 13264, E-mail: axel.schlagenhauf@medunigraz.at.
authors.forename: Axel
authors.initials: A
authors.lastname: Schlagenhauf
authors.forename: Harald
authors.initials: H
authors.lastname: Haidl
authors.forename: Bettina
authors.initials: B
authors.lastname: Leschnik
authors.forename: Hans-Joerg
authors.initials: HJ
authors.lastname: Leis
authors.forename: Akos
authors.initials: A
authors.lastname: Heinemann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Muntean
mesh_terms: D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000097:blood; D015232:Dinoprostone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation; D010979:Platelet Function Tests; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000037:antagonists & inhibitors / Q000097:blood; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000037:antagonists & inhibitors / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; C545647:PTGER3 protein, human; C545650:PTGER4 protein, human; D011448:Prostaglandin Antagonists; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D000242:Cyclic AMP; D015232:Dinoprostone
keywords: Cyclic AMP; neonate; platelet aggregation; prostaglandin E2; prostanoid receptor EP4