Erythropoiesis Abnormalities Contribute to Early-Onset Anemia in Patients with Septic Shock

• Published in: American journal of respiratory and critical care medicine Vol. 174; no. 1; pp. 51 - 57
• Main Authors: Claessens, Yann-Erick, Fontenay, Michaela, Pene, Frederic, Chiche, Jean-Daniel, Guesnu, Martine, Hababou, Cyrla, Casadevall, Nicole, Dhainaut, Jean-Franccois, Mira, Jean-Paul, Cariou, Alain
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01.07.2006; American Lung Association; American Thoracic Society
• Subjects: Adult; Aged, 80 and over; Anemia; Anemia - blood; Anemia - etiology; Anemia - physiopathology; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Apoptosis; Apoptosis - physiology; Biological and medical sciences; Blood; Bone marrow; Case-Control Studies; Cellulose; Drug toxicity and drugs side effects treatment; Emergency and intensive care: infection, septic shock; Erythroid Precursor Cells - physiology; Erythropoiesis - physiology; Female; Flow cytometry; Hemoglobin; Humans; Intensive care medicine; Ligands; Male; Medical sciences; Microscopy; Middle Aged; Pharmacology. Drug treatments; Receptors, Death Domain - blood; Receptors, Erythropoietin - blood; Sepsis; Shock, Septic - blood; Shock, Septic - complications; Shock, Septic - physiopathology; Toxicity: blood; Tumor necrosis factor-TNF; France; Shock; Erythropoiesis; Human; Infection; Intensive care; septic shock; Erythropoietin; Polypeptide; Anemia; Hemopathy; Resuscitation; Apoptosis
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200504-561OC

The intimate mechanisms of early onset anemia observed in critically ill patients with septic shock remain unclear. We investigated erythropoiesis abnormalities in this setting by studying morphologic, functional, and biochemical patterns of erythroid lineage. 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. 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. 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.