New insights into thrombopoiesis in neonatal sepsis

Thrombocytopenia is one of the most frequent hematologic abnormalities in the neonatal period, affecting about 18-35% of all patients admitted to the Neonatal Intensive Care Unit (NICU), with sepsis being among the most common causes of severe neonatal thrombocytopenia. It is unclear whether decreased platelet production or increased platelet consumption contributes to thrombocytopenia of septic neonates. To answer this question, we evaluated the effects of sepsis on neonatal thrombopoiesis using a panel of tests. This prospective case-control study was conducted on 50 neonates with culture-proven sepsis admitted to NICU at the Pediatrics Department, Ain Shams University Hospitals. Thirty healthy newborns were included as controls. The enrolled neonates were subjected to detailed history taking, thorough clinical examination, and laboratory investigations including complete blood count, C-reactive protein, blood cultures, and tests of thrombopoiesis; namely serum thrombopoietin (TPO) assay, flow cytometric analysis of reticulated platelet percentage (RP%), and calculation of absolute RP counts. Septic neonates comprised 24 males and 26 females with a mean gestational age of 36.0 +/- 3.1 weeks. Twenty-eight (56%) of the septic neonates were thrombocytopenic (platelets < 150 000/mu l). While platelet and RP counts were decreased, TPO and RP% were increased in septic neonates compared to healthy controls. Neonates with Gram-negative sepsis had the lowest platelet and RP counts and the highest TPO and RP% followed by those with fungal septicemia. Platelet counts showed inverse correlations with TPO and RP% and direct correlation with RP count. Our findings suggest that neonates respond to sepsis by up-regulating thrombopoiesis, where thrombocytopenia ensues when the rate of platelet consumption exceeds the rate of platelet production. Simultaneous measurements of serum TPO levels and RP% are helpful in discriminating hyperdestructive from hypoplastic thrombocytopenia among septic neonates.