Newborn platelets: Lower levels of protease-activated receptors cause hypoaggregability to thrombin

Abstract

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.

Thrombin receptor levels in platelet concentrates during storage and their impact on platelet functionality

“…We could show that PAR1 and PAR4 levels are lower in newborn PLTs compared to adult controls and that PAR receptor levels do correlate with PLT aggregation, when initiated with the specific agonist 14 . For the first time we could find a plausible explanation for the hyporeactivity of newborn PLTs to thrombin.…”

Platelet Transfusions in the Neonatal Intensive Care Unit

“…12 Recently, decreased expression of PAR-1 and PAR-4 receptors was described in neonatal platelets, thus explaining the decreased response to thrombin. 16,17 While this platelet hyporeactivity would have been expected to result in a bleeding tendency, Andrew et al . in 1999 reported that full term neonates had shorter bleeding times (BTs) than healthy adults.…”

Significant Hypo-Responsiveness to GPVI and CLEC-2 Agonists in Pre-Term and Full-Term Neonatal Platelets and following Immune Thrombocytopenia

“…The reduced response to adrenaline and thrombin has been attributed to decreased receptor expression, and in the case of thromboxane A 2 mimetic U46619, to defective G protein-coupled activity. 10 17 18 …”