Impaired platelet activity and hypercoagulation in healthy term and moderately preterm newborns during the early neonatal period

Abstract

BACKGROUND: Preterm newborns are at thrombohemorrhagic risk during the early neonatal period. Taking into account the lack of informative tools for the laboratory diagnosis of hemostasis disorders in newborns, our goal was to determine the baseline values of thrombodynamics and platelet functional activity in healthy term and moderately preterm newborns during the early neonatal period future potential clinical use of these tests. METHODS: Coagulation was assessed using an integral assay of thrombodynamics and standard coagulation assays, and platelet functional activity was estimated by flow cytometry. RESULTS: Hypercoagulation of newborns, represented by a significantly higher clot growth velocity and the presence of spontaneous clots in the thrombodynamics, was combined with platelet hypoactivity. Granule release, phosphatidylserine exposure, and the ability to change shape upon activation were decreased in the platelets of moderately preterm newborns. The platelet function remained at the same level over the first four days of life, whereas the hypercoagulation became less pronounced. CONCLUSIONS: The hemostasis of newborns is characterized by hypercoagulation combined with reduced platelet functional activity. Moderately preterm and term newborns do not differ in the parameters of coagulation, while some of the functional responses of platelets are lower in moderately preterm newborns than in term.

Impact of Reticulated Platelets on Platelet Reactivity in Neonates

“…While there are reports indicating hyporeactivity of neonatal platelets in response to agonists, such as ADP, epinephrine and collagen, there appears to be considerable data variability, which may be due to different sample types (cord blood verses peripheral blood), type of assay and procedures used to test platelet function. 3,23 In conditions associated with increased platelet turnover and higher levels of baseline platelet activation, such as immune thrombocytopenia patients, treatment with thrombopoietin receptor agonist resulted in a slight increase in platelet reactivity in response to thrombin, and the increase may be due to higher platelet count or higher platelet reactivity. 24 The reasons for the contrasting findings of platelet reactivity are unclear; however, neonates have higher immature platelet fraction, which are associated with lower threshold for granule exocytosis, increased expression of surface activation markers and hyperresponsiveness.…”

“…Neonates have a well-balanced hemostatic system, with shorter bleeding time and shorter closure times as demonstrated by platelet function analyzer-100 (PFA-100) measurements in response to collagen and ADP. 3,23 This apparently discordant finding of hypercoagulability and platelet hyporeactivity has been described to be due to the presence of large vWF multimers resulting from decreased cleavage activity of the zinc metalloprotease ADAMTS-13 in neonates. 1,3 The hyperaggregable milieu, from high levels of large vWF polymers, counterbalances the hyperstimulation of inhibitory signaling that contributes to the hyporeactivity of neonatal platelets.…”

“…Reticulated platelets are associated with reduced antiplatelet effects of aspirin and enhanced aspirin resistance, due to higher reactivity and uninhibited COX-1 activity. 23 As a result, an elevated count of immature reticulated platelets is inversely related to aspirin responsiveness. In addition, an elevated platelet turnover is associated with a greater-than-expected reduction in the antiplatelet effect, and consequently, increased platelet turnover could be a useful predictor of on-treatment platelet reactivity.…”

Specifities of the storage pool and morphology of platelets in children with unspecified hemorrhagic syndrome

“…Подходы к выявлению нарушений функции тромбоцитов у детей осложняются недостаточной изученностью возраст-зависимых различий. В частности, есть сообщения о том, что функциональные маркеры тромбоцитов, определяемые методом проточной цитометрии, могут быть значительно уменьшены [7,[18][19][20] или увеличены [20,21] у детей по сравнению со взрослыми.…”

Neonatal thrombosis: causes, pathogenesis, treatment features

“…Однако у детей наблюдается увеличение содержания тканевого фактора в периферических сосудах [22]. Одни исследователи относят это к механизмам, защищающим от травм, а другие полагают, что это следствие родового процесса и дальнейшего перерезания пуповины [23]. Кроме того, у новорожденных снижены концентрации естественных антикоагулянтов (антитромбина III и кофактора гепарина II) и уровни протеинов C и S, а концентрация α 2 -макроглобулина повышена [24,25].…”