Inflammation, anemia and Vitamin D status determine infant thrombocytosis risk

Abstract Extreme thrombocytosis (EXT, >1000×103 platelets/μl 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 (>500×103 platelets/μl) 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. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study was supported by the National Institutes of Health (T32 HL007150 to BMD, K99 HL156052 to CST, R00 HL177827 to CST) and the Childrens Hospital of Philadelphia. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of the University of Pennsylvania gave ethical approval for this work. The Institutional Review Board of the Childrens Hospital of Philadelphia gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes