Circulating thrombopoietin levels in neonates with infection

Thrombocytopenia is a commonly encountered hematologic complication in neon ates with sepsis. Thrombopoietin (TPO) is the principal physiologic regulat or of megakariocytopoiesis and platelet production. This study was carried out to determine whether variations in circulating TPO levels would occur i n infected neonates and/or if they would correlate with platelet counts. In a prospective study of 36 sick neonates (gestational age 24-42 wk) admitte d to a regional Neonatal Intensive Care Unit (NICU), blood was collected fo r TPO measurements and platelet counts on admission to the NICU, if infecti on was inferred, and at recovery before discharge. An additional group of 1 5 apparently healthy neonates was also studied (median postnatal age at the time of blood sampling for TPO assessment:4 d, range 1-10) as control. TPO was measured on plasma samples using a commercially available enzyme-immun osorbent assay (ELISA). On admission, the majority (21/36) of the sick neon ates had non-infectious diseases, 2 had early onset sepsis, and 13 had infe ction (defined as the presence of clinical signs of sepsis, abnormal leukoc yte counts or C-reactive protein values, and positive results on local cult ures, but negative blood culture results). During the hospital stay, 5 neon ates developed sepsis (positive blood culture) and 6 had infection (as prev iously defined) or necrotizing enterocolitis (NEC). The median TPO level (1 704 pg/ml, range 51-3912) was higher during sepsis (either early or late) t han during infection (included NEC) (198 pg/ml, range 21-2504), or non-infe ctious disease (659 pg/ml, range 0-2533), while platelet counts (median val ue 37,000 cell/mu l, range 15,000-486,000) were lower than during either in fection (included NEC) (median value 238,000 cells/mu l, range 49,000-655,0 00) or non-infectious disease (median value 110,000 cells/mu l, range 45,00 0-549,000). When infants had recovered from these illnesses, TPO concentrat ions markedly dropped (median value 59 pg/ml, range 0-825). These values we re similar to those found in the control neonates (median TPO level 85 pg/m l, range 43-620). In infected neonates (sepsis plus infection), TPO levels inversely correlated with platelet counts (r=-0.634, p=0.001) as did those of infants with non-infectious disease (r=-0.574, p=0.006), while there was no significant correlation between TPO levels and platelet counts in the s amples obtained after recovery or in the control infants. We conclude that infected neonates have high circulating TPO levels in the face of low plate let counts. Whether larger TPO concentrations following exogenous administr ation of recombinant TPO would restore the number of circulating platelets warrants further investigation.