Suppression of erythropoiesis in patients with chronic heart failure and anaemia of unknown origin: evidence of an immune basis

Abstract Aims Anaemia is a prevalent and adverse comorbidity in chronic heart failure (CHF) but its origins are frequently elusive. Diffuse inflammation is also prominent in CHF and a potent inhibitor of erythrocyte production. We tested the hypothesis that unexplained anaemia in CHF might be subseq...

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Bibliographic Details
Published in:International journal of cardiology 2013-07, Vol.166 (3), p.664-671
Main Authors: Okonko, Darlington O, Marley, Stephen B, Anker, Stefan D, Poole-Wilson, Philip A, Gordon, Myrtle Y
Format: Article
Language:English
Subjects:
Aged
Anaemia
Anemia - diagnosis
Anemia - epidemiology
Anemia - immunology
Anemias. Hemoglobinopathies
Biological and medical sciences
Cardiology. Vascular system
Cardiovascular
Cells, Cultured
Chronic Disease
Diseases of red blood cells
Erythropoiesis - immunology
Female
Heart
Heart failure
Heart Failure - diagnosis
Heart Failure - epidemiology
Heart Failure - immunology
Heart failure, cardiogenic pulmonary edema, cardiac enlargement
Hematologic and hematopoietic diseases
Humans
Inflammation
Male
Medical sciences
Middle Aged
Monocytes - immunology
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Summary:Abstract Aims Anaemia is a prevalent and adverse comorbidity in chronic heart failure (CHF) but its origins are frequently elusive. Diffuse inflammation is also prominent in CHF and a potent inhibitor of erythrocyte production. We tested the hypothesis that unexplained anaemia in CHF might be subsequent to diminished erythropoiesis as a result of an immune-mediated suppression of erythroid colony formation. Methods We studied 61 CHF patients and 20 healthy control subjects. Circulating primitive haematopoietic (CD34+ ) and erythroid precursor cells were quantified by flow cytometry. Circulating erythroid progenitors (BFU-E) were cultured in methylcellulose in the presence and absence of monocytes and sera, and with anti-TNFα neutralising antibodies. Results Despite higher erythropoietin levels, anaemic patients exhibited lower absolute reticulocyte counts and reticulocyte production indices (P < 0.001) than non-anaemic patients and healthy controls. Diminished erythropoiesis was paralleled by attenuated circulating CD34+ , erythroid progenitor and precursor cells in anaemic patients (all P < 0.01). Depletion of monocytes from cultures derived only from anaemic patients enhanced BFU-E growth (P = 0.03). Only the addition of monocytes and sera from anaemic patients suppressed autologous or allogeneic BFU-E colony formation (P = 0.02). Serum TNFα levels were highest in anaemic patients and anti-TNFα neutralising antibodies partly abrogated the inhibitory effects of anaemic sera on erythroid colony growth (P = 0.03). Conclusion Unexplained anaemia in patients with CHF results partly from suppressed erythropoiesis and monocytes, via a direct effect of TNFα on erythroid cells, orchestrate a degree of this suppression.
ISSN:0167-5273
1874-1754
DOI:10.1016/j.ijcard.2011.11.081