title: Red blood cell regeneration induced by subcutaneous recombinant erythropoietin: iron-deficient erythropoiesis in iron-replete subjects.
abstract: Limited red blood cell (RBC) regeneration often prevents collection of sufficient blood from autologous donors. We studied the effects of subcutaneous recombinant erythropoietin (rEPO) in subjects making frequent blood donations. Six healthy iron-replete male subjects took rEPO (200 U/kg) subcutaneously daily, and donated blood (450 mL) twice a week for 3 weeks. During a control study, these subjects also attempted twice-weekly blood donations without rEPO. Four other males given rEPO, including one with idiopathic hemochromatosis, waited until day 8 to begin blood donations. All healthy subjects took oral ferrous sulfate. Subcutaneous rEPO given with blood donations resulted in a marked reticulocytosis (mean peak value 568 +/- 159 x 10(9)/L v 235 +/- 77 x 10(9)/L, control study; P < .05), and enhanced RBC production at 28 days (1,208 +/- 227 mL v 719 +/- 161 mL, P < .05). rEPO in advance of blood donations was slightly less effective in normal subjects (941 +/- 139 mL, P < .05); however, the subject with hemochromatosis produced substantially more RBCs (1,764 mL) than any normal subject. rEPO-treated normal subjects (but not the rEPO-treated patient with hemochromatosis or untreated controls) produced iron-deficient RBCs with elevated zinc protoporphyrin levels and low hemoglobin content. These cells appeared within 1 week of rEPO administration and before laboratory confirmation of depleted iron stores. Thus, subcutaneous rEPO is an effective stimulant of erythropoiesis in nonanemic blood donors. However, in addition to eventual depletion of iron stores, early functional iron deficiency affects response to the drug.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA.
authors.forename: C
authors.initials: C
authors.lastname: Brugnara
authors.forename: L A
authors.initials: LA
authors.lastname: Chambers
authors.forename: E
authors.initials: E
authors.lastname: Malynn
authors.forename: M A
authors.initials: MA
authors.lastname: Goldberg
authors.forename: M S
authors.initials: MS
authors.lastname: Kruskall
mesh_terms: D001782:Blood Donors; D004906:Erythrocyte Count; D004909:Erythrocyte Indices; D004920:Erythropoiesis; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005293:Ferritins / Q000378:metabolism; D005296:Ferrous Compounds / Q000008:administration & dosage; D005492:Folic Acid / Q000097:blood; D006400:Hematocrit; D006432:Hemochromatosis / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000097:blood; D000090463:Iron Deficiencies; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012156:Reticulocytes / Q000166:cytology; D014168:Transferrin / Q000378:metabolism; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D005296:Ferrous Compounds; D006454:Hemoglobins; D011994:Recombinant Proteins; D014168:Transferrin; D004921:Erythropoietin; C020748:ferrous sulfate; D005293:Ferritins; D005492:Folic Acid; D007501:Iron; D014805:Vitamin B 12