Decreasing reticulocyte counts associated with declining post-dose erythropoietin plasma levels in anaemia of prematurity.

A prospective sequential, multicentre trial was conducted to determine the association between erythropoietin (EPO) plasma levels and the erythropoietic response to recombinant human erythropoietin (r-HuEPO) during long-term treatment of premature infants. Twenty-nine infants, gestational ages 26-34 weeks and postnatal ages more than 14 days, received 600 IU r-HuEPO per kg per week divided into three doses subcutaneously for haemoglobin levels less than 120 g/l or haematocrit less than 36% over a period of 4 weeks. Eight additional patients were studied for a total of 10 weeks. EPO plasma concentrations and haematologic parameters were measured prior to the onset of treatment and at 2-weekly intervals thereafter. Treatment with r-HuEPO resulted in a median increase in corrected reticulocyte counts of 2.5% (range 0.2-4.6%) above patient's baseline, thereafter a decrease was observed. In the 8 patients followed for 10 weeks reticulocyte counts declined significantly during weeks 6-10 when compared with the first 4 weeks (p < 0.005). Median 72-hour post-dose EPO plasma levels increased significantly (p < 0.0001) to 57.3 mU/ml (range 5.0-160) above patient's baseline after the first injection, but declined progressively thereafter until they approached baseline values at week 10. Conclusion: R-HuEPO treatment after the first month was associated with a decrease in post-injection plasma levels and a decrease in erythropoietic response. This decrease in erythropoietin's efficacy and the decline observed in post-dose EPO plasma levels may be causally related.