Ontogenesis of functional platelet subpopulations from preterm and term neonates to adulthood: The PLINIUS study

Abstract

Erythrocytes undergo a well-defined switch from fetal to postnatal circulation, mainly reflected by stage-specific expression of hemoglobin chains. Perinatal alterations of thrombopoiesis remain poorly understood. We assessed the ontogenesis of platelet phenotype and function from early prematurity to adults. We recruited 64 subjects comprising 7 extremely preterm (27-31 weeks gestational age), 25 moderately preterm (32-36 weeks) and 10 term neonates, 8 infants (<2a), 5 children (2-13a) and 9 adults (>13a). Blood was withdrawn at up to 3 different time points in neonates (t1: 0-2, t2: 3-7, and t3: 8-14 days after birth).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 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. While CD62P and CD63 surface exposure upon stimulation with TRAP-6, ADP or U46619 was unaltered or just slightly reduced in neonates, GPIIb/IIIa inside-out and outside-in activation was blunted, but showed a continuous increase until adulthood, correlating with expression of the GPIIb/IIIa regulating tetraspanin CD151. Platelet subpopulation analysis by automated clustering revealed that neonates presented with a CD63+/PAC1- pattern, followed by a continuous increase of CD63+/PAC-1+ platelets until adulthood. Our findings reveal that the number of platelet-monocyte and -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 platelet phenotype and function evolve continuously from neonates until adulthood.

Phosphoproteomics reveals content and signaling differences between neonatal and adult platelets

“…MARCKS also regulates leukocyte degranulation [73], and MARCKS-derived peptides antagonize coagulation in vivo by inhibiting interactions between factor Xa and phosphatidylserine residues [71]. Future experiments will test whether increased MARCKS abundance and/or phosphorylation can mechanistically explain the recently described dissociation between degranulation and GPIIb/IIIa conformational change in activated neonatal platelets [74].…”

Advances in Platelet-Dysfunction Diagnostic Technologies

“…Despite these methodologies, challenges persist because of the need for large blood samples and the limited availability of advanced tests in specialized laboratories, hindering prompt and accurate IPD diagnosis. However, recent improvements in diagnostic standards and quality control, especially in pediatric patients, have made significant progress in the field [ 124 , 126 , 127 , 128 , 129 , 130 , 131 , 132 ].…”