Erythropoiesis abnormalities contribute to early-onset anemia in patients with septic shock.
BACKGROUND
The intimate mechanisms of early onset anemia observed in critically ill patients with septic shock remain unclear.


OBJECTIVE
We investigated erythropoiesis abnormalities in this setting by studying morphologic, functional, and biochemical patterns of erythroid lineage.


METHODS
Erythroid lineage in the bone marrow from patients with septic shock who developed early-onset anemia was compared with that of healthy control subjects. Survival and proliferation capacities were quantified in both groups. Biochemical and flow cytometry patterns of apoptosis were dissected by exploring antiapoptotic (erythropoietin [Epo] receptor-dependent) and proapoptotic (death receptor-dependent) pathways.


RESULTS
Erythroid lineage was morphologically similar in both groups. Apoptosis of glycophorin-A-positive erythroid precursors was increased in patients versus control subjects as assessed by labeling with annexin V (26.1 +/- 8.8 vs. 3.1 +/- 2.9%, p < 0.05) or 3-3'-dihexyloxacarbocyanine iodide (55.9 +/- 10.5 vs. 19.1 +/- 5.4%, p < 0.05), respectively. This was associated with significant overexpression of Fas on erythroid precursors and higher tumor necrosis factor-alpha plasma levels in patients with septic shock vs. control subjects. Moreover, growth capacities of late erythroid progenitors of burst-forming unit erythroids (BFU-Es) at Day 10 were impaired in the presence of serum from patients with septic shock as compared with the effect of serum from control subjects (27 +/- 12 vs. 109 +/- 27 per 10(5) seeded cells, respectively; p < 0.001). Saturating concentrations of recombinant human Epo (rHuEpo) restored growth capacity of patients' BFU-Es (72 +/- 14 per 10(5) seeded cells) in autologous conditions of serum.


CONCLUSIONS
Early-onset anemia that may be observed in patients with septic shock is associated with defective erythropoiesis related to an excess of apoptosis that can be counterbalanced in vitro by rHuEpo.
Medical Intensive Care Unit, Cochin Hospital, APHP Université Paris-Descartes, 27 rue du Faubourg Saint-Jacques, F-75679 Paris, Cedex 14, France. alain.cariou@cch.ap-hop-paris.fr.
Yann-Erick
YE
Claessens
Michaëla
M
Fontenay
Frédéric
F
Pene
Jean-Daniel
JD
Chiche
Martine
M
Guesnu
Cyrla
C
Hababou
Nicole
N
Casadevall
Jean-Francçois
JF
Dhainaut
Jean-Paul
JP
Mira
Alain
A
Cariou
D000328:Adult; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000209:etiology* / Q000503:physiopathology*; D017209:Apoptosis / Q000502:physiology; D016022:Case-Control Studies; D015672:Erythroid Precursor Cells / Q000502:physiology*; D004920:Erythropoiesis / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053218:Receptors, Death Domain / Q000097:blood; D017467:Receptors, Erythropoietin / Q000097:blood; D012772:Shock, Septic / Q000097:blood / Q000150:complications* / Q000503:physiopathology*
D053218:Receptors, Death Domain; D017467:Receptors, Erythropoietin