Impaired Mobilization of Intracellular Calcium in Neonatal Platelets

Abstract

Abnormalities in platelet functions including aggregation and the release reaction have long been recognized to be present in neonatal platelets. Because calcium is an important mediator of many platelet functions, we have investigated the mobilization of calcium in neonatal platelets. All umbilical cord blood samples were obtained from healthy, full term gestations. Changes in cytoplasmic calcium levels were monitored using Fura-2 as a fluorescent probe. Fura-2-loaded washed platelets were stimulated with the agonists collagen (2 micrograms/mL) or thrombin (1.0 U/mL). When compared with adult controls, intracellular calcium release in the platelets of the neonate was significantly impaired in response to these agonists. Mean levels for calcium release in adults versus neonates in response to collagen were 168 +/- 120 nM (+/-SD, n = 10), and 61 +/- 69 nM (n = 7, p < 0.05). A decrease in response to thrombin was also observed [1296 +/- 503 nM (n = 8) in adults versus 603 +/- 482 nM (n = 7) in neonates, p < 0.025]. Results similar to those observed with unpaired neonatal and adult platelets were also obtained when neonatal platelets (n = 5) were compared with their paired maternal controls. In further studies, we have documented that the calcium content of the dense tubular system was normal in the neonatal platelet, indicating that the observed impairment in calcium mobilization in the neonate was not due to a decrease in calcium stores. The previously documented abnormalities in neonatal platelet function appear to be due to the impaired mobilization of this important intracellular mediator.

Platelet Function of Newborns as Tested by Cone and Plate(let) Analyzer Correlates with Gestational Age

“…Platelet aggregation depends mainly on the GPIIb-IIIa receptor, which presents at lower levels in neonatal platelets compared to adults. This is compatible with previous studies that showed relative neonatal platelet function impairment [8, 9, 11,23,24,25,26]. …”

“…Some of these alterations recently studied include impaired platelet-dense granule release in neonates [7], a decreased number of GPIIb/IIIa receptors upon resting neonatal platelets, a defect of GPIb internalization [11, 21, 22], a reduced number of α-adrenergic receptors in newborn platelets [23] and deficient TxA 2 synthesis and response [24]. The poor response of neonatal platelets to TxA 2 may be related to impaired postreceptor signal transduction pathway [25, 26]. Interestingly, when compared to full-term neonatal platelets, the platelets obtained from premature neonates showed an even poorer response [9].…”

Platelet Transfusions in the Neonatal Intensive Care Unit

“…12,13 The underlying mechanisms responsible for the decreased platelet responses are different for each agonist. Specifically, the lack of response to epinephrine is explained by the presence of fewer α2-adrenergic receptors on neonatal platelets, 14 the diminished response to collagen is likely a consequence of impaired calcium mobilization, 15 and the reduced response to thromboxane is due to differences in signaling downstream from the receptor in neonatal platelets. 12 Recently, decreased expression of PAR-1 and PAR-4 receptors was described in neonatal platelets, thus explaining the decreased response to thrombin.…”

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

“…Cord blood-derived neonatal and adult platelets had similar levels of baseline calcium (11). However, intracellular calcium release in neonatal platelets was reduced when compared to adult platelets in response to either collagen or thrombin.…”

“…However, intracellular calcium release in neonatal platelets was reduced when compared to adult platelets in response to either collagen or thrombin. These differences were hypothesized to be secondary to a deficiency in IP 3 production and interaction of IP 3 with its receptor on the dense tubular system that ultimately is required for calcium release (11). Mobilization of calcium was found to be impaired in neonatal platelets in response to a thromboxane analogue.…”