Age‐related changes in thrombopoietin in children: reference interval for serum thrombopoietin levels

Abstract

Summary. We studied thrombopoietin (TPO, Mpl ligand) values using a sensitive ELISA in 254 serum samples obtained from disease-free children and adult volunteers. TPO was detected in all samples, and its values ranged widely from 0´25 to 9´18 fmol/ml. When analysed by dividing the subjects into 11 age groups, the mean TPO levels from birth to 1 month of age were increased (3´73±5´92 fmol/ml). The highest values were found 2 d after birth; TPO levels then gradually decreased to adult levels (0´83 fmol/ml). The relationship between TPO values and platelet counts was not signi®cant in all subjects (r 0´27) or in children alone (r 0´12). In children > 1 month of age a 95% reference interval for serum TPO values was determined from 0´58 to 3´27 fmol/ml. A signi®cant correlation was found between TPO values in serum and plasma; serum TPO values À0´257 4´039´plasma TPO values (r 0´951, P < 0´001, n 22). This study is the ®rst to report agedependent changes in blood TPO levels throughout child development. Serum TPO values were signi®cantly high up to 1 month of age and were correlated with plasma TPO levels.Keywords: thrombopoietin, children, cord blood, serum, plasma.Thrombopoietin (TPO, c-Mpl-ligand) is a glycoprotein that primarily regulates megakaryocyte development and platelet production (Kaushansky, 1998). The binding to c-Mpl on megakaryocytes/platelets regulates the blood levels of TPO (Kuter & Rosenberg, 1995), and the synthesis of TPO mRNA is constitutive in the liver and kidney (Kaushansky, 1998). Elevation of endogenous TPO values has been observed in disorders with reduced platelet/megakaryocyte mass, including aplastic anaemia (Emmons et al, 1996;Kojima et al, 1997;Marsh et al, 1996) and chemotherapy-induced thrombocytopenia (Chang et al, 1996;Meng et al, 1996;Nichol et al, 1995). Increased TPO levels precede thrombocytosis in an in¯ammatory disorder, Kawasaki disease (Ishiguro et al, 1998), and are caused by decreased expression of c-Mpl in essential thrombocythaemia (Horikawa et al, 1997) and idiopathic myelo®brosis (Moliterno et al, 1998).These effects of TPO in thrombopoiesis are similar to the key roles played by erythropoietin in erythropoiesis and by granulocyte colony-stimulating factor (G-CSF) in granulopoiesis (Kaushansky, 1998). In contrast to extensive studies on endogenous levels of erythropoietin and G-CSF (Ishiguro et al, 1996;Krafte-Jacobs et al, 1995;Ruth et al, 1990), the changes in blood TPO levels throughout child development remain unknown. The absence of age-adjusted reference values in children has hindered the interpretation of TPO values in sick children. To expand therapeutic trials from adults (Kaushansky, 1998) to children, basic data on TPO in disease-free populations are necessary. The recent development of a highly-sensitive ELISA has enabled detection of blood TPO in healthy individuals (Tahara et al, 1996;Tamura et al, 1998). We measured blood TPO levels from birth through adulthood. Our results revealed that changes in serum TPO values are age-dependent and are correlate...

Serum thrombopoietin level and thrombocytopenia during the neonatal period in infants with Down's syndrome

“…We compared our TPO results with reference intervals earlier evaluated in healthy infants. 20 We showed that TPO in DS infants rose from birth to day 2, and thereafter gradually decreased by the end of the neonatal period. This temporal change is concordant with kinetics in term non-DS infants.…”

“…Our study included two late preterm infants, but as they were just before term, they can be considered as term from a hematological perspective. 20 and found no differences of TPO concentrations between DS and historical non-DS subjects 20 at any sample periods. Figure 2 illustrates the kinetic changes of TPO concentration in 12 DS infants, dividing two subgroups: those without Thrombopoietin and thrombocytopenia in Down's syndrome K Matsubara et al thrombocytopenia (non-thrombocytopenic group, n ¼ 5) and those who had a platelet count <150 Â 10 9 per liter at least once (thrombocytopenic group, n ¼ 7).…”

“…As normal controls, we used the results of our earlier works, which evaluated the reference interval of serum TPO levels throughout childhood. 20 As significant correlation of TPO values between serum and plasma was shown, 20 we determined blood TPO levels in serum in this study.…”

Hematologic Abnormalities in Severe Neonatal Necrotizing Enterocolitis: 25 Years Later

“…24 Circulating levels of Tpo were high in cord blood and the first days of postnatal life, 25 but were relatively lower in thrombocytopenic neonates vs thrombocytopenic adults. 25,26 Serum Tpo levels in neonates were variable, but tended to be lower in sepsis or infection, 27,28 suggesting an inability to upregulate Tpo production in response to thrombocytopenia associated with these conditions. Data support that plasma Tpo levels in thrombocytopenic neonates are blunted in response to low platelet counts, similar to relatively low plasma Epo levels in the anemia of prematurity.…”

Developmental Changes in Soluble CD40 Ligand

“…Alternatively, differences in ligand levels might be simply attributed to differences in platelet number because historic studies of platelet ranges reveal that platelet counts in all pediatric age groups are statistically higher than in adults (25). Although there appeared to be no correlation between an individual adult's platelet count and the plasma sCD40L level in this study, the small sample size and wide confidence intervals undermine the confidence with which such a statement can be made.…”