EFFICACY OF DIFFERENT DOSING REGIMENS FOR RECOMBINANT-HUMAN-ERYTHROPOIETIN IN A SIMULATED PERISURGICAL SETTING - THE IMPORTANCE OF IRON AVAILABILITY IN OPTIMIZING RESPONSE

PURPOSE: The goal of this study was to develop a short-term, practical , yet effective regimen for the perioperative use of recombinant human erythropoietin (r-HuEPO) as an alternative to autologous blood donati on and/or homologous transfusion. In addition, changes in iron kinetic s during accelerated erythropoiesis were examined. PATIENTS AND METHOD S: A randomized trial was performed on 24 healthy, iron-replete men. S ubjects were given r-HuEPO in one of three dosage schedules, receiving a total dose of 1200 U/kg r-HuEPO subcutaneously: Group I-300 U/kg on Days 1, 4, 7, and 10; Group II-400 U/kg on Days 1, 5, and 9; Group II I--600 U/kg on Days 1 and 10, All subjects received 300 mg of elementa l iron orally each day for 10 days beginning on Day 1. Complete blood counts (CBC), absolute reticulocyte counts, serum ferritin, serum iron , serum total iron-binding capacity (TIBC), and serum transferrin rece ptor protein concentrations were measured periodically during the 24-d ay study period. RESULTS: All groups showed a statistically significan t increase in hematocrit, hemoglobin, and absolute reticulocyte count. There was no significant difference in response among the three group s with respect to hemoglobin and hematocrit. The mean maximum increase s in hematocrit were 5.4 +/- 1.7, 6.0 +/- 2.1, and 7.2 +/- 2.6 in grou ps I, II, and III, respectively. The increase in hematocrit positively correlated with log baseline ferritin (r = 0.682, p <0,001). Administ ration of r-HuEPO was associated with a highly significant (p less tha n or equal to 0.0005) 74% decrease in serum ferritin, as well as a mar ked decrease in percent saturation of TIBC from 39% +/- 14% to 14% +/- 4% (p less than or equal to 0.0005). This was despite the fact that s ubjects lost less than 250 mL of blood as a result of venipunctures du ring the entire course of the study. CONCLUSION: Each of these r-HuEPO dose schedules provides an effective, convenient regimen for perisurg ical use. However, ''normal'' iron stores for basal erythropoiesis may not always be sufficient to supply optimal amounts of iron for the ac celerated erythropoiesis associated with acute r-HuEPO administration, even with oral iron supplementation. Nonetheless, these findings prov ide support for further study of the use of r-HuEPO as an alternative to autologous blood donation in the perisurgical setting.