Background Associations among inflammatory cytokines, erythropoietin, and anemia in critically ill septic patients remain unclear. This study tested the hypothesis that elevated inflammatory cytokines and decreased erythropoietin would be associated with iron-restricted anemia while accounting for operative blood loss, phlebotomy blood loss, and red blood cell (RBC) transfusion volume. Methods Prospective observational cohort study of 42 critically ill septic patients. Hemoglobin (Hb) at sepsis onset and hospital discharge were used to calculate ΔHb. Operative blood loos, phlebotomy blood loss, and RBC transfusion volume were used to calculate adjusted ΔHb (AdjΔHb) assuming 300 mL RBC = 1 g/dL Hb. Patients with AdjΔHb >0 (+AdjΔHb, n=18) were compared to patients with AdjΔHb ≤0 (-AdjΔHb, n=24). Results Plasma TNF-alpha, G-CSF, IL-6, IL-8, and erythropoietin, erythrocyte mean corpuscular volume (MCV), and serum transferrin receptor (sTfR) were measured on days 0, 1, 4, 7, and 14. Patients with –AdjΔHb had significantly higher day 14 levels of IL-6 (37.4 vs. 15.2 pg/mL, p
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