Abstract 2361: Bone Marrow Dysfunction In Chronic Heart Failure Patients Contributes To Impaired Erythropoiesis
Background: We hypothesised that anemia in chronic heart failure (CHF) patients is caused by bone marrow dysfunction.
Methods: Bone marrow was harvested during cardiac surgery from 17 patients with CHF (LVEF 32 ± 1.8 %) and 17 age matched control patients with normal cardiac function (LVEF ≥ 55%). Early hematopoietic progenitor cells (CD34+) and committed erythroid cells (CD71bright), apoptosis (Annexin-V+/DAPI+) and EPO-receptor (EPO-R) density were quantified by FACS. Erythroid and myeloid colony formation of isolated CD34+ cells was assessed in methylcellulose containing incrementing doses of erythropoietin (EPO) or myeloid cytokines. After 14 days Burst Forming Units Erythroid (BFU-E) or granulocyte and monocyte colonies were quantified.
Results: Patients with CHF had lower hemoglobin levels and 35% of CHF patients had anemia. The numbers of CD34+ and CD71bright cells were 2 fold lower in CHF patients (P < 0.05). Throughout the EPO dose-response range, CD34+ cells of CHF patients produced a 3-fold lower number of BFU-E colonies than controls (figure 1⇓, P < 0.02). Concomittantly, myeloid colony formation was 2 fold lower in CHF patients as well (P < 0.05). This was associated with markedly increased apoptosis (P < 0.01), but equivalent EPO-receptor expression. Lower BFU-E numbers were independently associated with higher NTproBNP levels (R = − 0.5, P = 0.03). However, BFU-E formation was comparable in anemic and non-anemic CHF patients (P = 0.8).
Conclusions: General bone marrow dysfunction in CHF patients contributes to impaired erythropoiesis. Although this might render patients more susceptible to anemia, it does not exclusively explain its occurrence.