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The authors examined the impact of parenteral iron and recombinant human erythropoietin-β (rHuEPO-β) administered in the bilateral total knee replacement arthroplasty (TKRA), on postoperative anemia and transfusion requirements in iron-deficient patients.A total of 108 iron-deficient patients were randomly assigned to two groups: Group C (control) or Group IE (200 mg of iron sucrose intravenously over 1 hr and 3000 IU of rHuEPO-β subcutaneously during the operation and during the postoperative period if the hemoglobin [Hb] level was 70-80 g/L). One or 2 units of blood were transfused to patients in both groups according to postoperative Hb level (between 60 and 70 g/L or betweeen 50 and 60 g/L, respectively). Perioperative laboratory and clinical outcomes (Hb, iron variables, postoperative bleeding amount, and number of units of RBCs transfused and incidences) were documented.Although preoperative Hb and the amount of postoperative bleeding were comparable in the two groups, Hb levels at 1, 2, and 3 days and at 2 and 6 weeks postoperation were significantly higher in Group IE. Furthermore, the transfusion rate was significantly lower in Group IE (20.4% vs. 53.7%, p = 0.011) and the mean number of red blood cell units transfused was markedly lower in Group IE (0.2 ± 0.5 vs. 0.8 ± 0.8, p = 0.005). Postoperative iron, ferritin, and transferrin saturation levels were significantly higher in Group IE.Treatment with parenteral iron and low-dose rHuEPO-β in bilateral TKRA effectively attenuated anemia and decreased transfusion requirements in iron-deficient patients.