Abstract

OBJECTIVE Red blood cell (RBC) transfusions can suppress erythropoiesis. On this basis, RBC transfusions administered to very low birth weight (VLBW) neonates potentially render them more likely to qualify for a subsequent transfusion.STUDY DESIGN We hypothesized that 'late' (>14 days after birth) RBC transfusions given to VLBW neonates result in a decrease in reticulocyte count persisting for at least 7 to 10 days. We also hypothesized that a single dose of darbepoetin given along with the transfusion would have the opposite effect, increasing the reticulocyte count for at least 7 to 10 days. To test this, we conducted a single-centered randomized trial with 20 VLBW neonates who, according to our transfusion guidelines, qualified for a late transfusion.RESULT VLBW infants about to receive a late RBC transfusion were randomized (1:1) to also receive vs not receive (controls) a single subcutaneous dose of darbepoetin (10 µgkg(-1)). Reticulocyte counts diminished significantly in the controls (a drop of 85±62 x 10(3) µl(-1) (mean±s.d.) at 7 to 10 days), but increased significantly in the darbepoetin recipients (an increase of 177±120 x 10(3) µl(-1) at 7 to 10 days, P<0.0001). At 7 to 10 days after the transfusion, hematocrits of the controls were 8.1±4.9 points above their pre-transfusion values and of the darbepoetin group were 12.4±2.7 points above their pre-transfusion values (P=0.033).CONCLUSION This was a limited-scope, single-centered, randomized trial intended to pilot-test a new concept in neonatal transfusion practice. Namely, we tested whether a late RBC transfusion suppressed reticulocytosis and whether a concomitant single dose of darbepoetin counteracted that suppression. Using the pilot data presented in this study, larger trials can now be designed to address meaningful clinical outcomes such as transfusion avoidance using this approach.

Abstract

Objective: Darbepoetin is longer acting and more potent than recombinant erythropoietin (rEpo). In certain situations, preterm neonates might benefit from rEpo, and for such patients darbepoetin would require fewer doses at a lower cost. However, the proper dose and dosing interval have not been established. Study design: We performed a prospective trial in two level III Neonatal Intensive Care Units. Patients <32 weeks gestation at birth, with a birth weight (BW) <1500g, were eligible for participation if they were >21-days-old and had a hemoglobin (Hgb) concentration <=10. 5g/dl. In all, 12 were to receive a single subcutaneous (s. c. ) dose at either 1 or 4 mug/kg. Once before the dose was given, and at two preset intervals after, blood was obtained for immature reticulocyte fraction (IRF) and absolute reticulocyte count (ARC). Once before and at four preset intervals after, blood was obtained for pharmacokinetic studies. Results: The 12 subjects had BWs of 1129+/-245g (mean+/-SD), were 29. 2+/-1. 2 weeks gestation at delivery, and were 43+/-12 days old with an Hgb concentration of 9. 6+/-1. 0g/dl when the darbepoetin was given. Six received 1 mu;g/kg and six 4 mug/kg. The IRF increased (p<0. 05) as did the ARC (p<0. 05). The increases in IRF were somewhat greater among the 4 mug/kg recipients (P =0. 06). The highest recorded concentrations of drug occurred 6 to 12 hours after administration. The combined 6 and 12 hours values were 185+/-106mU/ ml in the 1 mug/kg group vs 597+/-238 in the 4 mug/kg group (p<0. 002). The t 1/2 was 26 hours (range 10 to 50). The biovailability-normalized clearance was 19ml/hour/kg (range 5 to 54). Conclusions: A single s. c. dose of darbepoetin given to preterm neonates accelerated effective erythropoiesis. The pharmacodynamic and pharmacokinetic findings suggest that darbepoetin dosing in neonates would require a higher unit dose/kg and a shorter dosing interval than are generally used for anemic adults. Copyright © 2011 Elsevier B. V. , Amsterdam. All Rights Reserved.