Nucleated Red Blood Cell Emergence-Time in Newborn Lambs Following a Dose of Darbepoetin Alfa

Background: Nucleated red blood cells (NRBC) are very uncommon in the blood of children and adults, but small numbers are not rare in neonates on the day of birth. Elevated NRBC counts in neonates can be seen following erythropoietin dosing. Limited studies in human neonates suggest the time-interval between erythropoietin dosing and the first appearance of NRBC in the blood (the “NRBC emergence-time”) is in excess of 24 hours. Methods: We made serial blood counts (Sysmex veterinary analyzer) on ten newborn lambs; five were dosed with darbepoetin (10 μg/kg), and five were dosed with a vehicle-control to assess the NRBC emergence time under relatively controlled laboratory conditions. Results: The first appearance of NRBC was at 24 h (2757 ± 3210 NRBC/μL vs. 0/μL in controls). Peak was 48-72 h (16,758 ± 8434/μL vs. 0/μL in controls), followed by fewer at 96 hours (7823 ± 7114/μL vs. 0/μL in controls). Similarly, reticulocytes peaked at 48-72 h (113,094 ± 3210/μL vs. 10,790 ± 5449/μL in controls), with no changes in platelets or leukocytes. Conclusion: The NRBC emergence time in newborn lambs is similar to reports from newborn humans. By extrapolation, if a neonate has a high NRBC at birth, the erythropoietic stimulus likely occurred within the interval 24 to perhaps 96+ hours prior to birth.