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Treatment of Experimental Acute Severe Anemia with Recombinant Human Erythropoietin

Treatment of Experimental Acute Severe Anemia with Recombinant Human Erythropoietin

Anesthesiology Abstracts of Scientific Papers Annual Meeting (2000): Abstract No 495

INTRODUCTIONS: Unpredictable significant blood loss is encountered in cases of severe trauma and/or major surgery. Clinically, the perioperative administration of recombinant human erythropoietin (rHuEPO) is still restricted to selective operations in which patients' Hb level is between 10 and 13 grams/dL. The benefits of rHuEPO therapy is unclear when stated after surgical and/or traumatic blood loss. The purpose of this study was to investigate the potential application and efficacy of rHuEPO after experimental severe acute anemia. METHODS: 50 Sprague-Dawley rats, weighing 350g, were used in the study. Blood was removed through a carotid catheter and replaced with 6% hetastarch. The Hb was reduced to 50% of baseline on the first day. The following day, blood depletion continued until Hb was reduced to 30% (4mg/dL) of baseline. Blood pressure and heart rate were maintained within normal range during the phlebotomy. The anemic rats were randomly divided into two groups: the control group without any treatment (dietary iron) and the rHuEPO group, in which rats received rHuEPO (300 U/kg/day) subcutaneously daily for 10 days postphlebotomy. Hb, hematocrit (Hct), and reticulocyte counts (Ret) as well as serum iron were measured from baseline to 28 days postphlebotomy. RESULTS: Hb in both groups showed a gradual increase after phlebotomy. The Hb in the rHuEPO group grew much faster than that in the control group between days 6 and 14 (p < 0.05). It took 12 days for Hb's in the rHuEPO group recovery to return to baseline compared with 14 days in the control group. The pattern of Hct parallels the change of reticulocytes and began to increase on day 3, peaked on day 7 (34.37 +- 4.33 % in the control group; 46.84 +- 4.34 % in the rHuEPO group), and returned to baseline levels (3.74 +- 2.56 %) on day 21 in both groups. The rHuEPO group experienced a greater rate of increase in the mean reticulocyte count starting before day 3 to day 7 (p < 0.05). The decrease of circulating iron after phlebotomy was induced in both groups, but much lower levels were reached in the rHuEPO-treated group (p < 0.05). CONCLUSIONS: Post hemorrhage administration of rHuEPO in experimental severe acute anemia leads to faster restoration of reticulocytosis and hemoglobin. Normal iron stores are unable to keep up with the enhanced response to rHuEPO. Iron supplement is needed to optimizes the erythropoiesis enhanced by rHuEPO. This study suggests the potential application of rHuEPO trauma in severe blood loss setting and could reduce the possibility of patients' exposure to allogeneic transfusion.

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