Inflammation, anemia and Vitamin D status determine infant thrombocytosis risk

Extreme thrombocytosis (EXT, >1000x103 platelets/l blood) occurs in infants due to infection, inflammation, and/or anemia. EXT can present diagnostic dilemmas, sometimes prompting invasive testing and anticoagulation therapy. Our prior worked identified heightened EXT rates in hospitalized infants compared with older children, but this analysis largely excluded expreterm infants at increased risk for infections and anemia - factors that promote thrombocytosis and EXT. The objectives of this study were 1) to define EXT rates, etiologies, and sequelae among infants hospitalized in tertiary neonatal intensive care units (NICUs) to assist clinical decision-making and 2) to ascertain factors that drive thrombocytosis and EXT in preterm and full-term patients. Retrospective analysis of thrombocytosis (>500x103 platelets/l) and EXT cases among 20,818 infants hospitalized in tertiary NICUs from 2011-2023 revealed thrombocytosis in 3% of all patients (8% of preterm infants). Both estimates were significantly lower than the incidence of thrombocytosis in pediatric patients in a quaternary NICU (15%). EXT rates were also markedly diminished in our tertiary unit (0.08% vs 0.5% in our quaternary NICU). Thrombocytosis was associated with leukocytosis and relative anemia, but not with thrombotic or bleeding complications. Vitamin D deficiency can drive thrombocytosis in adults and Vitamin D level was inversely corelated with platelet count among infants with thrombocytosis. Our findings suggest that Vitamin D supplementation among ex-preterm infants reduces thrombocytosis and EXT incidence, as opposed to developmental differences and/or organ immaturity in these patients. These results provide important context for clinical interpretations and responses to thrombocytosis in the preterm infant population.