PDF(Pubmed)
Abstract：
Erythrocytes undergo a well-defined switch from fetal to postnatal circulation, which is mainly reflected by the stage-specific expression of hemoglobin chains. Perinatal alterations in thrombopoiesis are poorly understood. We assessed the ontogenesis of platelet phenotype and function from early prematurity to adulthood. We recruited 64 subjects comprising 7 extremely preterm (27-31 weeks gestational age), 25 moderately preterm (32-36 weeks), 10 term neonates, 8 infants (<2 years), 5 children (2-13 years), and 9 adults (>13 years). Blood was withdrawn at up to 3 different time points in neonates (t1: 0-2, t2: 3-7, and t3: 8-14 days after birth). We found that the expression levels of the major surface receptors for fibrinogen, collagen, vWF, fibronectin, and laminin were reduced but correlated with decreased platelet size, indicating a normal surface density. Although CD62P and CD63 surface exposure upon stimulation with TRAP-6, ADP, or U46619 was unaltered or only slightly reduced in neonates, GPIIb/IIIa inside-out and outside-in activation was blunted but showed a continuous increase until adulthood, correlating with the expression of the GPIIb/IIIa regulating tetraspanin CD151. Platelet subpopulation analysis using automated clustering revealed that neonates presented with a CD63+/PAC-1- pattern, followed by a continuous increase in CD63+/PAC-1+ platelets until adulthood. Our findings revealed that the number of platelet-monocyte and platelet-neutrophil aggregates, but not platelet-lymphocyte aggregates, is increased in neonates and that neonatal aggregate formation depends in part on CD62P activation. Our PLatelets In Neonatal Infants Study (PLINIUS) provides several lines of evidence that the platelet phenotype and function evolve continuously from neonates to adulthood.
摘要：
红细胞经历了从胎儿到出生后循环的明确转换，主要表现为血红蛋白链的阶段性特异性表达。围产期血小板生成的改变仍然知之甚少。我们评估了从早期早产到成人的血小板表型和功能的个体发育。我们招募了64名受试者，包括7名极度早产（27-31周孕龄），25例中度早产（32-36周）和10例足月新生儿，8名婴儿（<2a），5名儿童（2-13a）和9名成人（>13a）。新生儿在多达3个不同的时间点（t1：0-2，t2：3-7和t3：出生后8-14天）抽取血液。我们发现纤维蛋白原的主要表面受体的表达水平，胶原蛋白，vWF,纤连蛋白,层粘连蛋白减少了，但与血小板大小减少相关，表明表面密度正常。虽然新生儿在用TRAP-6、ADP或U46619刺激后CD62P和CD63表面暴露没有改变或只是轻微减少，GPIIb/IIIa由内而外激活被钝化，但表现出持续的增长，直到成年，与GPIIb/IIIa调节四跨膜蛋白CD151的表达相关。通过自动聚类的血小板亚群分析显示，新生儿呈现CD63+/PAC1-模式，随后CD63+/PAC-1+血小板持续增加直至成年。我们的研究结果表明，血小板单核细胞和中性粒细胞聚集体的数量，但新生儿血小板-淋巴细胞聚集体不增加，新生儿聚集体的形成部分取决于CD62P的激活。我们的新生儿血小板研究（PLINIUS）提供了几条证据，表明血小板表型和功能从新生儿到成年期持续发展。
