Haematology Research, Murdoch Childrens Research Institute, Melbourne, Vic., Australia; The University of Melbourne, Parkville, Vic., Australia.
Br J Haematol. 2015 Feb;168(4):526-32. doi: 10.1111/bjh.13153. Epub 2014 Sep 30.
Platelets are crucial subcellular elements of haemostasis at sites of vascular injury and are also known to be immune mediators in pathological thrombosis. Despite the integral role of platelets in many disease processes, there is very little information available on platelet function and response to agonists in healthy children. We recently reported important differences in the interaction of platelets with monocytes in the circulation, including increased formation of monocyte-platelet aggregates (MPAs) without concomitant increase in P-selectin expression. Our current study investigates parameters of platelet activation (PAC-1 binding and P-selectin expression) and MPA formation in response to a range of physiologically relevant platelet agonists in healthy children compared to healthy adults. All parameters were significantly higher in children in response to sub-maximal concentrations of thrombin receptor activator peptide and adenosine diphosphate, reflecting an age-specific difference in agonist-stimulated platelet reactivity in children. The results of our study challenge the general assumption that platelet reactivity in children is similar to adults. This finding is fundamental to investigating the role of platelets in diseases of childhood and pathogenesis of adult-based diseases that have their origins in childhood. Our findings underscore the need for age-specific reference ranges for platelet function in children rather than extrapolation from adult data.
血小板是血管损伤部位止血的关键亚细胞成分,也是病理性血栓形成中的免疫介质。尽管血小板在许多疾病过程中都起着重要作用,但关于健康儿童血小板功能和对激动剂的反应的信息却非常有限。我们最近报道了血小板与循环中的单核细胞相互作用的重要差异,包括单核细胞-血小板聚集体(MPA)的形成增加,而 P-选择素表达没有相应增加。我们目前的研究调查了与健康成年人相比,健康儿童对一系列生理相关血小板激动剂的血小板活化(PAC-1 结合和 P-选择素表达)和 MPA 形成的参数。在儿童中,对低浓度的血栓酶受体激活肽和二磷酸腺苷的所有参数均显著升高,这反映了儿童在激动剂刺激的血小板反应性方面存在年龄特异性差异。我们研究的结果对儿童血小板反应性与成年人相似的一般假设提出了挑战。这一发现对于研究儿童期疾病中血小板的作用以及起源于儿童期的成年疾病的发病机制具有重要意义。我们的研究结果强调了在儿童中建立血小板功能的年龄特异性参考范围的必要性,而不是从成人数据推断。