Unexpected persistence of platelet hyporeactivity beyond the neonatal period: a flow cytometric study in neonates, infants and older children.
ABSTRACT Previous studies, using flow cytometry, have reported a lower platelet reactivity in neonates compared to adults. Only few studies were carried out in older children, and results were controversial in terms of age to reach adult platelet function. We studied a total of 125 healthy neonates, infants and older children, and 15 adults. alphaIIbbeta3 expression on resting and activated platelets was lower in all children, with an impaired capability of alphaIIbbeta3 activation (PAC1 and bound fibrinogen). This defect was observed until the age of fifteen with a gradual recovery with age. In neonates, we observed a defect of GPIalpha internalization, and demonstrated that this defect persisted in older children as well. In contrast with alphaIIbbeta3 integrin activation, we did not observe a gradual age-dependent recovery. These unexpected results point out the need for reference values in childhood.
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ABSTRACT: Platelets are subcellular fragments which circulate in blood and have well established roles in thrombosis and haemostasis in adults. Upon activation, platelets undergo granule exocytosis and express P-Selectin on the cell membrane which binds a ligand on monocytes, leading to monocyte-platelet aggregation. Elevated circulating monocyte-platelet aggregates in adults are linked to atherothrombosis, but have not been investigated in children where thrombosis is less common. This study aimed to measure monocyte-platelet aggregate formation in children using whole blood flow cytometry. Monocyte-platelet aggregates as well as activation and granule exocytosis of platelets were measured in healthy adults (n = 15, median age 28 years) and healthy children (n = 28, median age 7 years). Monocyte-platelet aggregates in healthy children were elevated compared to healthy adults (37.8±4.4% vs 15.5±1.9% respectively, p<0.01). However, this was not accompanied by any difference in platelet activation (PAC-1 binding 6.8±1.5% vs 6.3±2.0% respectively, p = ns) or granule exocytosis (P-selectin expression 4.4±0.5% vs 3.1±0.5% respectively, p = ns). Despite comparable numbers of platelets bound per monocyte (GPIb MFI 117.3±13.7 vs 130.9±28.6 respectively, p = ns), surface P-selectin expression per platelet-bound monocyte was lower in children compared to adults. We therefore provide the first data of elevated monocyte-platelet aggregates in healthy children.PLoS ONE 01/2013; 8(6):e67416. · 3.73 Impact Factor
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ABSTRACT: This prospective, single-center study aimed to evaluate the platelet response during cardiopulmonary bypass (CPB) surgery in a large cohort of children up to 6 years of age. Blood samples were drawn at four time points: after induction of anesthesia, after initiation of the CPB, before protamine, and immediately after chest closure. The study recruited 60 children requiring CPB for surgical repair of congenital heart defects. The platelet count decreased throughout CPB surgery, but during the same period, platelet activity increased. The more pronounced decrease in platelet count observed in children younger than 1 year compared with that of children 1 to 6 years of age was not associated with an age-specific change in platelet activity. The overall increase in platelet function observed in this study could provide a mechanism that compensates for the decrease in platelet count. This study provides a new foundation for future studies investigating requirements of platelet supplementation in the setting of pediatric CPB surgery.Pediatric Cardiology 08/2011; 33(1):55-9. · 1.20 Impact Factor
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ABSTRACT: Little data on pediatric percent platelet aggregation (%PA) exist in the literature, particularly in cardiac patients and in response to clopidogrel. The objectives were to estimate the %PA range expected in pediatric patients and to measure the clopidogrel effect on %PA in the PICOLO (Platelet Inhibition in Children on Clopidogrel) trial. To estimate a neonatal/infant %PA response range, %PA induced by 5 µM adenosine diphosphate (ADP) was assessed using light transmission aggregometry in 16 cord and 11 normal adult blood samples and prior to clopidogrel therapy in 49 neonatal and 49 infant/toddler cardiac patients enrolled in PICOLO. The %PA induced by 5 µM thrombin receptor-activating peptide (TRAP) was also assessed for 10 neonates and 21 infants/toddlers enrolled in PICOLO and compared with 11 adult samples. Percent inhibition of platelet aggregation (%IPA) induced by 5 µM ADP at steady-state clopidogrel levels was assessed in 33 neonates and 39 infants/toddlers. ADP-induced %PA was lowest in cord blood samples, intermediate in study neonates and infants/toddlers, and highest in adults. Similarly, TRAP-induced platelet aggregation was lower in neonates and infants/toddlers than adults. For all groups, %PA and %IPA were highly variable, with 11% of neonates and 13% of infants/toddlers showing <10% IPA. In conclusion, ADP- and TRAP-induced %PA is lower in pediatric cardiac patients than normal adults, but highly variable in both. The lower baseline %PA may explain why the pediatric clopidogrel dose providing 30-50% IPA (0.20 mg/kg/day) is lower than a simple weight-based extrapolation of the adult dose (75 mg/day) providing similar inhibition.Platelets 02/2012; 23(6):430-8. · 2.24 Impact Factor