KINETICS OF RETICULOCYTE MATURITY FRACTIONS AND INDEXES AND IRON STATUS DURING THERAPY WITH EPOETIN-BETA (RECOMBINANT-HUMAN-ERYTHROPOIETIN)IN CARDIAC-SURGERY PATIENTS

We evaluated the changes in reticulocyte maturity fractions and indice s, as measured by flow cytometry, during preoperative treatment with r ecombinant human erythropoietin (epoetin beta) in cardiac surgery pati ents, A total of 72 patients was enrolled in this double-blind, random ized, placebo-controlled clinical trial and assigned to the two treatm ent groups (5 x 500 U/kg bodyweight epoetin beta or placebo intravenou sly over 14 days preoperatively). Therapy with epoetin beta produced c ontinuous increases in hematocrit/hemoglobin, in the most mature fract ion of reticulocytes (LR), and in reticulocyte count, In the first tre atment week there were parallel increases in the fraction of most imma ture reticulocytes (HR) and in the reticulocyte mean cell volume, Duri ng the second week of treatment the reticulocyte mean cell hemoglobin content (CHr) decreased, but CHr was independent of all iron parameter s, affecting neither the reticulocyte fractions nor the hematocrit/hem oglobin increase, The total preoperative rise in hematocrit correlated with the rises in LR fraction (P = 0.0270) and reticulocyte count (P = 0.0486) during the first week of treatment, Whereas in the epoetin b eta patients the preoperative change in HR fraction showed negative co rrelations with transferrin saturation at baseline (P = 0.0058) and wi th the preoperative change in iron (P = 0.0113), the preoperative chan ge in the LR fraction correlated positively with transferrin at baseli ne (P = 0.0115). Postoperatively, the reticulocyte parameters revealed that the onset of increased stimulation of erythropoiesis did not occ ur in the placebo patients until the second postoperative day, whereas erythropoietic activity in the epoetin beta patients was much higher during the postoperative period as well, as a result of the preoperati ve stimulation of erythropoiesis. The reticulocyte parameters measured by flow cytometry permitted an objective analysis of erythropoietic a ctivity during treatment with epoetin beta and in all patients postope ratively. Further studies in various types of epoetin beta therapy are needed in order to clarify the value of these reticulocyte parameters for identification of iron deficiency and optimization of epoetin bet a treatment regimen. (C) 1997 Wiley-Liss, Inc.