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Red Blood Cell Precursor Mass as an Independent
Determinant of Serum Erythropoietin Level
Mario Cazzola,
Roberta Guarnone,
Paola Cerani,
Esther Centenara,
Andrea Rovati, and
Yves Beguin
From the Department of Internal Medicine and Medical Therapy, Section
of Internal Medicine and Medical Oncology, and the Department of
Medicine, Division of Hematology, University of Liège,
Liège, Belgium.
Serum erythropoietin (sEpo) concentration is primarily related to
the rate of renal production and, under the stimulus of hypoxia,
increases exponentially as hemoglobin (Hb) decreases. Additional
factors, however, appear to influence sEpo, and in this work, we
performed studies to evaluate the role of the red blood cell precursor
mass. We first compared the relationship of sEpo with Hb in patients
with low versus high erythroid activity. The first group included 27 patients with erythroid aplasia or hypoplasia having serum transferrin
receptor (sTfR) levels < 3 mg/L (erythroid activity < 0.6 times
normal), while the second one included 28 patients with  -thalassemia
intermedia having sTfR levels > 10 mg/L (erythroid activity > 2 times normal). There was no difference between the two groups with
respect to Hb (8.3 ± 1.6 v 8.0 ± 1.3 g/dL, P > .05), but sEpo levels were notably higher in patients with low
erythroid activity (1,601 ± 1,542 v 235 ± 143 mU/mL,
P < .001). In fact, multivariate analysis of variance
(ANOVA) showed that, at any given Hb level, sEpo was higher in patients with low erythroid activity (P < .0001).
Twenty patients undergoing allogeneic or autologous bone marrow
transplantation (BMT) were then investigated. A marked increase in sEpo
was seen in all cases at the time of marrow aplasia, disproportionately high when compared with the small decrease in Hb level. Sequential studies were also performed in five patients with iron deficiency anemia undergoing intravenous (IV) iron therapy. Within 24 to 72 hours after starting iron treatment, marked decreases in sEpo (up
to one log magnitude) were found before any change in Hb level. Similar
observations were made in patients with megaloblastic anemia and in a
case of pure red blood cell aplasia. These findings point to an inverse
relationship between red blood cell precursor mass and sEpo: at any
given Hb level, the higher the number of red blood cell precursors, the
lower the sEpo concentration. The most likely explanation for this is
that sEpo levels are regulated not only by the rate of renal
production, but also by the rate of utilization by erythroid cells.
Blood, Vol. 91 No. 6 (March 15), 1998:
pp. 2139-2145
© 1998 by The American Society of Hematology.
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