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Red blood cell regeneration induced by subcutaneous recombinant
erythropoietin: iron-deficient erythropoiesis in iron-replete subjects [see
comments]
C Brugnara, LA Chambers, E Malynn, MA Goldberg and MS Kruskall
Department of Pathology, Brigham and Women's Hospital, Boston, MA.
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.
Volume 81,
Issue 4,
pp. 956-964,
02/15/1993
Copyright © 1993 by The American Society of Hematology
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