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The Anemia of Primary Autonomic Failure and its Reversal with Recombinant Erythropoietin

Italo Biaggioni, MD; David Robertson, MD; Sanford Krantz, MD; Mark Jones, MD; and Virginia Haile, RN
[+] Article and Author Information

From Vanderbilt University and the Department of Veterans Affairs Medical Center, Nashville, Tennessee. Requests for Reprints: Italo Biaggioni, MD, Clinical Research Center, AA-3228 MCN, Vanderbilt University, Nashville, TN 37232-2195. Acknowledgments: The authors thank Mrs. Dorothea Boemer and Jane Estrada for editorial assistance in the preparation of this manuscript. Grant Support: In part by National Institutes of Health grants RR00095, HL14192, and HL 36984, and National Aeronautics and Space Administration grants NAGW-3854 and NCG 9-563.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1994;121(3):181-186. doi:10.7326/0003-4819-121-3-199408010-00004
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Objective: To determine if chronic sympathetic deprivation is associated with anemia and a low erythropoietin response.

Design: Survey of the prevalence and characteristics of anemia in patients with severe primary autonomic failure.

Setting: A referral service for autonomic failure in a tertiary teaching hospital.

Patients: 84 patients with primary autonomic failure who had symptomatic orthostatic hypotension.

Intervention: Open-label trial with human recombinant erythropoietin.

Results: Anemia was present in 32 of 84 patients (38%; 95% CI, 27% to 50%). Plasma norepinephrine levels, measured in patients standing upright, were lower in the patient group with lower hemoglobin levels. Mean values in 22 patients with a hemoglobin level of less than 120 g/L were as follows: hemoglobin, 108 g/L (range, 87 to 118 g/L); hematocrit, 0.33; corrected reticulocyte counts, 0.008; mean corpuscular volume, 89 fL (89 microns3); serum iron, 16.5 µmol/L (92 µg/dL); total iron binding capacity, 43.3 µmol/L (242 µg/dL); ferritin, 184 µg/L; serum vitamin B12, 410 pmol/L (556 pg/mL); and serum folate, 22.7 nmol/L (10 ng/mL). No relation was found between serum erythropoietin and blood hemoglobin levels. In seven of nine patients with autonomic failure who had hemoglobin levels less than 120 g/L, serum erythropoietin levels decreased below the 95% confidence interval corresponding to patients with iron deficiency anemia. Therapy with recombinant erythropoietin improved mean hemoglobin levels (from 108 to 133 g/L) in all patients treated (n = 5) at relatively low doses (25 to 50 units/kg body weight, subcutaneously, three times a week).

Conclusions: Our data support the hypothesis that the sympathetic nervous system stimulates erythropoiesis in humans because anemia is a frequent occurrence in patients with severe autonomic failure and is associated with a blunted erythropoietin response.

Figures

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Figure 1.
Relation between hemoglobin concentrations and serum immunoreactive erythropoietin concentrations in 27 patients with autonomic failure.EPOPP

Individual values are shown by solid circles. No linear association was noted between serum erythropoietin ( ) and hemoglobin levels in patients with autonomic failure (r = −0.3; = 0.13). For comparison, the linear regression and 95% confidence intervals from a control group composed of patients with iron deficiency anemia and normal persons are shown by dashed lines (EPO = 112 −7.5 x hemoglobin; r = −0.7; = 0.003).

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Figure 2.
Plasma norepinephrine levels in patients standing upright according to severity of anemia.PAFMSANEP

Open bars indicate patients with pure autonomic failure ( ), hatched bars indicate those with multiple system atrophy ( ), and closed bars indicate all patients. Blood hemoglobin levels were less than 12 g/dL in group 1, were 12 to 13 g/dL in group 2, and were greater than 13 g/dL in group 3. Plasma norepinephrine ( ) levels were measured in patients standing upright for 30 minutes. A difference was noted in plasma norepinephrine levels among groups ( = 0.002 by ANOVA). To convert norepinephrine levels to SI units (nmol/L), divide by 169.2.

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