Current issues of ACP Journal Club are published in Annals of Internal Medicine


Recombinant human erythropoietin reduced the need for transfusions in adults who had elective hip arthroplasty

ACP J Club. 1993 Sept-Oct;119:46. doi:10.7326/ACPJC-1993-119-2-046

Source Citation

Canadian Orthopedic Perioperative Erythropoietin Study Group. Effectiveness of perioperative recombinant human erythropoietin in elective hip replacement. Lancet. 1993 May 15;341:1227-32.



To compare the effectiveness of perioperative erythropoietin with placebo on transfusion requirements in patients who had elective hip arthroplasty.


Randomized, double-blind, placebo-controlled trial with 3-week follow-up after surgery.


5 university centers in Canada.


208 patients (mean age 63 y, 104 men) scheduled for elective unilateral arthroplasty who were < 86 years of age. Exclusion criteria were preoperative hemoglobin concentration ≤ 110 or ≥ 160 g/L, systolic blood pressure (BP) > 180 mm Hg, diastolic BP > 100 mg Hg, history of seizure or deep venous thrombosis (DVT), myocardial infarction or stroke in the previous year, any condition that might interfere with response to erythropoietin, or severe systemic illness.


All patients received oral iron sulfate for 21 days before surgery and injection of either placebo or erythropoietin (300 mg/kg body weight subcutaneously up to a maximum of 30 000 mg per dose) starting 10 days before surgery. Group 1 (n = 78) received 14 days of placebo. Group 2 (n = 77) received 14 days of erythropoietin. Group 3 (n = 53) received placebo for days 10 to 6 preoperatively and erythropoietin for the next 9 days. Study drugs were stopped if systolic BP increased > 40 mm Hg in 1 day or was > 200 mm Hg, diastolic BP was > 105 mm Hg, seizures occurred, or if hemoglobin levels were > 180 g/L or > 30 g/L over baseline.

Main outcome measures

Intraoperative or postoperative transfusion or hemoglobin < 80 g/L. Secondary outcomes were mean perioperative transfusion needs, hemoglobin, reticulocyte counts, pain by visual analog scales, length of hospital stay, patient-reported well-being, and DVT by venogram or ultrasonography.

Main results

Transfusion or low hemoglobin values occurred in 46% of patients in group 1, 23% in group 2, and 32% in group 3 (P = 0.003). The change (placebo) in hemoglobin levels from baseline to the day before surgery was -2.6 for group 1, +8.8 for group 2, and +2.2 g/L for group 3. The corresponding reticulocyte counts were 72, 327, and 170 × 10/L. The groups did not differ for self-reported pain, shortness of breath, energy level, mean length of hospital stay, nursing intensity scores, incidence of DVT, blood pressure, or adverse events.


Erythropoietin was well tolerated and reduced the need for intraoperative or postoperative transfusions in adults who had elective hip arthroplasty.

Sources of funding: Medical Research Council of Canada and Robert Wood Johnson Pharmaceutical Research Institute, Canada.

For article reprint: Dr. A. Laupacis, Clinical Epidemiology Unit, Loeb Research Institute, Ottawa Civic Hospital, 1053 Carling Avenue, Ottawa, Ontario K1Y 4E9, Canada. FAX 613-761-5351.


In 1989, Levine and colleagues reported on the successful perioperative use of erythropoietin in an animal model (1). Now, the Canadian Orthopedic Perioperative Erythropoietin Study Group has done a placebo-controlled, randomized clinical trial on the perioperative use of recombinant human erythropoietin. The study showed that erythropoietin was effective in decreasing the need for red cell transfusion in patients who had elective hip arthroplasty. These data are important.

Because blood transfusion will never be totally free from risk, current transfusion medicine philosophies are emphasizing decreased exposure to allogeneic (homologous) blood. Autologous collection, directed donor programs, and blood salvage programs have all increased dramatically in the past decade. These approaches, however, have their own inherent problems. Even autologous collection is not without risk and, for many reasons, not all patients are able to take advantage of this option.

Erythropoietin has been used successfully to treat various types of anemia as well as to increase the number of autologous units collected from an individual patient (2). One of the biggest drawbacks to using erythropoietin is its cost, but as the clinical indications for erythropoietin expand and become better defined, it may be possible for more patients to avoid allogenic blood transfusion. Further study is required, but I think we are just now seeing the tip of the erythropoietin iceberg.

Ronald E. Domen, MD
Cleveland Clinic FoundationCleveland, Ohio, USA


1. Levine EA, Gould SA, Rosen AL, et al. Perioperative recombinant human erythropoietin. Surgery. 1989;106:432-8.

2. Tabbara IA. Erythropoietin: biology and clinical applications. Arch Intern Med. 1993;153:298-304.