Newborn platelets: lower levels of protease-activated receptors cause hypoaggregability to thrombin.
Newborn platelets show in vitro hypoaggregability to thrombin. Sensitivity of platelets to such a potent agonist is crucial for a functional clot formation. Nevertheless, newborns have an excellent hemostasis. We wanted to investigate the reason for this impairment by comparatively analysing levels of receptors known to be involved in thrombin signaling in newborn and adult platelets. Platelets of adult and cord blood were isolated, washed, and lysed. Resulting protein samples were separated by SDS-PAGE and blotted on nitrocellulose membranes. Receptors were visualized using immunodetection and evaluated densitometrically. Thrombin receptor activating peptide induced platelet aggregation was measured in citrated whole blood on a Multiplate analyzer. Statistical analysis was performed using SPSS 16.0. Significantly lower levels of protease-activated receptors (PAR1, PAR4) and higher levels of glycoprotein Ibα (GPIbα) were found in newborn platelets as compared to adult platelets. Platelet aggregation was lower in newborn samples than in adult controls and values correlated with the corresponding PAR levels. Our results suggest that lower levels of protease-activated receptors contribute to the poor thrombin induced aggregation observed with newborn platelets, which can not be compensated by higher levels of GPIbα.
Schlagenhauf
A
A
Department of Pediatrics, Medical University of Graz, Austria.
Schweintzger
S
S
Birner-Gruenberger
R
R
Leschnik
B
B
Muntean
W
W
D000328:Adult; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D010446:Peptide Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism*; D044463:Receptor, PAR-1 / Q000378:metabolism*; D018179:Receptors, Thrombin / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology*
D010446:Peptide Fragments; D019038:Platelet Glycoprotein GPIb-IX Complex; D020033:Protein Isoforms; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; C086309:thrombin receptor peptide SFLLRNP; D013917:Thrombin; C112908:protease-activated receptor 4