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

Abstract

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.