Environmental Research, Section B

Abstract

C-mpl ligand or thrombopoietin (Tpo) is increasingly recognised as the major regulator of platelet homeostasis in humans. Relatively little is known about Tpo in the fetus and neonate but no evidence has yet been found to suggest any fundamental difference in Tpo structure, function and regulation in the fetus and neonate compared to older age groups. Tpo mRNA transcripts have been detected in the fetus as early as 6 weeks post conception and the liver appears to be the main site of Tpo production in both the fetus and neonate. The vast majority of healthy newborns have detectable levels of circulating Tpo and raised Tpo levels are commonly, but not consistently, found in thrombocytopenic neonates. In adults receptor binding and subsequent metabolism of Tpo is proposed as the main method of regulation of the circulating Tpo level. Preliminary studies in neonates showing increased Tpo levels most often during thrombocytopenia accompanied by reduced megakaryocytopoiesis supports this concept. In addition to this demonstrable fetal and neonatal endogenous Tpo production megakaryocyte progenitor and precursor cells from the fetus and from preterm and term newborns proliferate and differentiate extensively in-vitro in response to exogenous Tpo. Furthermore a recent study has shown a marked rise in platelet count in newborn rhesus monkeys administered one form of recombinant Tpo. Although these studies remain at an early stage together these findings strongly suggest that, as in adults, Tpo is the major regulator of platelet homeostasis in the fetus and neonate. Thrombocytopenia is common in sick neonates and progress in understanding this important clinical problem is likely to be greatly enhanced by the current and future research into Tpo production, function and regulation in the healthy and thrombocytopenic fetus and neonate.