Published ahead of print on March 30, 2006, doi:10.1164/rccm.200504-561OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200504-561OC
Erythropoiesis Abnormalities Contribute to Early-Onset Anemia in Patients with Septic ShockMedical Intensive Care Unit, INSERM U567, Department of Emergency Medicine, and Laboratory of Hematology, Hôpital Cochin; Faculté de Médecine, Université Paris-Descartes; Laboratory of Hematology, Hôtel-Dieu, Paris; and Ortho Biotech France, Inc., Issy-les-Moulineaux, France Correspondence and requests for reprints should be addressed to Alain Cariou, M.D., Medical Intensive Care Unit, Cochin Hospital, APHP Université Paris-Descartes, 27 rue du Faubourg Saint-Jacques, F-75679 Paris, Cedex 14, France. E-mail: alain.cariou{at}cch.ap-hop-paris.fr Rationale: The intimate mechanisms of early onset anemia observed in critically ill patients with septic shock remain unclear. Objectives: 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.
Measurements and Main 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- 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.
Key Words: anemia • apoptosis • erythropoiesis • erythropoietin • septic shock This article has been cited by other articles:
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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 105 seeded cells, respectively; p < 0.001). Saturating concentrations of recombinant human Epo (rHuEpo) restored growth capacity of patients' BFU-Es (72 ± 14 per 105 seeded cells) in autologous conditions of serum. 
