Platelet Activation during the Early Neonatal Period

İrken, Gülersu; Mutafoglu, Kamer; Olgun, Nur; Ündar, Bülent; Akkoç, Nurullah; Özkan, Hasan; Akyol, Faize; Çevik, Necla

doi:10.1159/000013974

Cited by 12 publications

(6 citation statements)

References 20 publications

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“…The neonatal platelet phenotype differs from that of adults in-vitro , exhibiting hypoaggregability with many commonly used agonists such as ADP, epinephrine, thrombin, and thromboxane analogs (Mull and Hathaway, 1970 ; Israels et al, 1990 ; Rajasekhar et al, 1994 ). Platelet preactivation during accouchement and resultant refractoriness has been proposed, but in agreement with other research groups we found no increase in activation markers on neonatal platelets after delivery (Nicolini et al, 1994 ; Grosshaupt et al, 1997 ; Irken et al, 1998 ). Instead, multifactorial impairments in signal transduction of neonatal platelets have been shown to cause hyporeactivity.…”

Section: Introductionsupporting

confidence: 93%

Polyphosphate in Neonates: Less Shedding from Platelets and Divergent Prothrombotic Capacity Due to Lower TFPI Levels

et al. 2017

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Background: The neonatal hemostatic system exhibits a fragile balance featuring lower levels of clotting factors as well as inhibitors. Neonatal platelets show in-vitro hypoaggregability, but neonates exhibit well-functioning primary and secondary hemostasis despite this impairment. Recently, polyphosphate shed by activated platelets has been shown to induce a prothrombotic shift on the plasmatic coagulation system of adults. The impact of platelet derived polyphosphate might differ in neonates due to aforementioned peculiarities.Aims: We aimed to comparatively determine polyphosphate content and release from adult and neonatal platelets and to determine its impact on thrombin generation in plasma from adult and cord blood.Methods: Polyphosphate was extracted from adult and neonatal platelet lysates and releasates using silica spin-columns and quantified with a DAPI based fluorescence assay. The impact of exogenous polyphosphate in various concentrations (208–0.026 μg/ml) on thrombin generation was evaluated in plasma from adult and cord blood as well as in adult plasma with reduced tissue factor pathway inhibitor (TFPI) levels using calibrated automated thrombography.Results: Polyphosphate content was comparable in both groups, but the fraction of released polyphosphate upon stimulation with thrombin receptor activating peptide was lower in neonatal samples (adult: 84.1 ± 12.9%; cord: 58.8 ± 11.2%). Relative impact of polyphosphate on lag time of thrombin generation was higher in adult samples compared to samples from cord blood (adult: 41.0% [IQR: 35.2–71.8%] of vehicle; cord: 73.4% [IQR: 70.2–91.4%] of vehicle). However, in samples from cord blood, lower concentrations of polyphosphate were required to obtain maximal impact on thrombin generation (adult: 26 μg/ml; cord: 0.814 μg/ml). PolyP affected thrombin generation in adult plasma similarly to cord plasma, when the TFPI concentration was reduced to neonatal levels.Conclusion: Differences in the impact of polyphosphate on adult and neonatal coagulation are largely caused by differences in TFPI levels. Lower polyphosphate release from neonatal platelets, but lower optimum concentration to drive neonatal plasmatic hemostasis emphasizes the well-matched, but fragile interplay between platelets and coagulation in newborns. A potential developmental mismatch should be considered when transfusing adult platelets into neonates.

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Section: Introductionsupporting

confidence: 93%

Polyphosphate in Neonates: Less Shedding from Platelets and Divergent Prothrombotic Capacity Due to Lower TFPI Levels

et al. 2017

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“…It has been argued that degranulation of neonatal platelets occurs during delivery and that platelets become refractory and consequently hyporesponsive to potent agonists. However, in agree-ment with other research groups we could find no signs of partial activation of neonatal platelets during delivery (11)(12)(13).…”

Section: Introductionsupporting

confidence: 92%

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

Schlagenhauf¹,

Haidl²,

Leschnik³

et al. 2015

Thromb Haemost

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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.

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“…34 More recent studies using flow cytometric measurements of activation markers found no increase in the numbers of circulating degranulated platelets in either the fetus or the neonate, and the mode of delivery did not influence these findings. 67,69,70,[73][74][75] The hyporesponsiveness of neonatal platelets therefore does not appear to be the result of partial activation or degranulation during labor or delivery.…”

Section: Platelet Activation During Deliverymentioning

confidence: 99%

Neonatal Platelet Function

Israels

Rand²,

Michelson³

2003

Semin Thromb Hemost

102

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Healthy newborns maintain normal circulating platelet counts, with a platelet ultrastructure that does not differ from adults. In vitro assessments of intrinsic platelet function, however, have demonstrated transient hyporesponsiveness that is most marked in platelets from preterm infants. Decreased responses were originally considered to be the result of platelet activation and degranulation during labor and delivery, but more recent studies of platelet activation markers have not supported this theory. Decreased activation responses are due to relative deficiencies of phospholipid metabolism, calcium mobilization, granule secretion, and aggregation. These result in turn from differences in intrinsic signal transduction in the neonatal platelet compared with the adult. In contrast, there is enhanced platelet adhesion due to the presence in neonatal plasma of larger, more functionally potent von Willebrand factor multimers. These ultralarge multimers may result from decreased activity of von Willebrand factor-cleaving protease in neonatal plasma and are associated with shorter bleeding times and Platelet Function Analyser-100 closure times in neonates. In the immediate newborn period, this enhanced platelet adhesion may compensate for the decreased intrinsic platelet activation in healthy neonates, but may leave sick neonates at increased risk of bleeding.

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Platelet Activation during the Early Neonatal Period

Cited by 12 publications

References 20 publications

Polyphosphate in Neonates: Less Shedding from Platelets and Divergent Prothrombotic Capacity Due to Lower TFPI Levels

Polyphosphate in Neonates: Less Shedding from Platelets and Divergent Prothrombotic Capacity Due to Lower TFPI Levels

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

Neonatal Platelet Function

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