Effects of subcutaneous recombinant human erythropoietin in normal subjects: development of decreased reticulocyte hemoglobin content and iron-deficient erythropoiesis.
The present study evaluates the properties of the reticulocytes produced in healthy volunteers after treatment with different regimens of recombinant human erythropoietin (r-HuEPO). Twenty-four subjects were randomly assigned to one of three different subcutaneous (SC) r-HuEPO (Protcrit; Ortho Biotech) administration protocols (I: 300 U/kg on days 1, 4, 7, 10; II: 400 U/kg on days 1, 5, 9; III: 600 U/kg on days 1, 10) with oral iron supplementation (Niferex; 150 mg, twice a day). The characteristics of the reticulocytes produced were examined with a flow cytometry method that allows measurements of individual reticulocyte cell volume, hemoglobin concentration, and hemoglobin content. Administration of SC r-HuEPO was associated with a significant increase in the production of reticulocytes. The hemoglobin content of reticulocytes (CHr, in picograms of hemoglobin per cell) in the three groups was 28.5 +/- 1.0, 28.2 +/- 0.5, and 28.5 +/- 1.3, respectively, at baseline, decreased to 24.6 +/- 1.6 (p < 0.001), 24.5 +/- 2.3 (p < 0.001), and 27.5 +/- 1.8 (not significant) at day 10, and returned to baseline after r-HuEPO was discontinued (28.8 +/- 0.9, 28 +/- 0.8, and 28.8 +/- 1.4, respectively, at day 22). The percentage of reticulocytes with cell hemoglobin content less than 23 pg was taken as an indicator of iron-deficient erythropoiesis. At baseline, 5.6% +/- 2.7%, 6.9% +/- 3.4%, and 8.3% +/- 3.8% of reticulocytes had less than 23 pg hemoglobin in groups I, II, and III, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Brugnara
C
C
Department of Pathology, Brigham and Women's Hospital.
Colella
G M
GM
Cremins
J
J
Langley
R C
RC
Schneider
T J
TJ
Rutherford
C J
CJ
Goldberg
M A
MA
D004920:Erythropoiesis; D004921:Erythropoietin / Q000494:pharmacology*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007279:Injections, Subcutaneous; D000090463:Iron Deficiencies; D008297:Male; D009994:Osmolar Concentration; D011994:Recombinant Proteins; D012016:Reference Values; D012156:Reticulocytes / Q000166:cytology / Q000378:metabolism*
D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin