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Blood Transfusion In Primary Hip And Knee Arthroplasty. Preoperative Treatment With Recombinant Human Erythropoietin

 Luis A. Gómez-Navalón*, Pedro Zorrilla*, Antonio Marín*, Cristóbal Martínez*, Jose A. Salido*

* General Hospital of Ciudad Real. Ciudad Real. Spain

Address for Correspondence:

Dr. Luis Alejandro Gómez-Navalón
Residencial vergel, 9
13004-Ciudad Real. Spain
Tel: 0034- 926-231626


J.Orthopaedics 2007;4(4)e5


Joint prosthetic surgery, particularly of the hip and knee, is one of the most common orthopedic procedures performed today. The increase in life expectancy and an aging population demanding an increasingly higher quality of life are factors that have contributed to this phenomenon. This type of surgery is known to cause a loss of blood that often requires a blood transfusion,1 which is not without potential risks and complications such as transmission of infectious diseases (mainly hepatitis and AIDS),2,3 manipulation errors, fever, increased rate of infections, etc., without forgetting that a proportion of the population refuses to have a blood transfusion because of religious beliefs.4 In order to palliate these problems, it is attempted to reduce blood transfusion needs as much as possible by various procedures, including preoperative autologous blood donation, the use of blood recovery systems, agents that reduce bleeding, minimally invasive surgery and stimulation of erythrocyte production with erythropoietin (EPO) among others.

          The present study analyzed the reduction in transfusion requirements achieved by preoperative administration of EPO in patients undergoing primary hip and knee arthroplasty.

Material and Methods :

From December 1, 2001 to July 31, 2005, 717 primary total prostheses (426 total knee and 291 total hip prostheses) were implanted in our Orthopedics Department (Figure 1). Of these, 93 implanted patients (12.9%) had preoperative hemoglobin (Hb) levels less than or equal to 13 g/dl, and were included initially in the study. These patients were applied the exclusion criteria for treatment with EPO listed in Table 1.

          Four patients were excluded for poorly controlled hypertension, 1 for acute medical disease, 11 for cardiovascular disease, 2 for blood disease, and 8 for concomitant immunosuppressant medication (high-dose corticosteroids and/or immunosuppressants).

          The remaining 67 patients received treatment with EPO on days -21, -14 and -7 prior to surgery at a dose of 40,000 IU epoetin alpha. On day 0 (24 hours before surgery), a new blood test was done and if Hb levels were lower than 15 g/dl patients received a fourth dose. All patients received oral supplements of 200 mg iron/day.

          In order to harmonize the transfusion criteria on an objective and statistically quantifiable basis, the indication to perform blood transfusion was considered to be Hb levels <8.5 g/dl, as these levels are widely accepted in the literature5-7 as indication for transfusion. The patients receiving transfusion with Hb>8.5 g/dl were excluded from the study. Patients meeting the exclusion criteria indicated by Salido8 (Table 2) were also excluded, as this removes possible causes of Hb reduction other than surgery itself. In this way, 2 patients who had liver cirrhosis and 4 patients who were transfused during resuscitation in the operating room with Hb levels > 8.5 g/dl were excluded from the study.

A total of 61 patients met all the above requirements and were included in the study.

          All patients received antithrombotic prophylaxis with calcium nadroparin (Sanofi Winthrop) from 12 hours before to 2 months after surgery.

The study was approved by our Institutional Review Board and the subjects gave informed consent to participate in the study.

Pre- and postoperative Hb levels, the increase in Hb levels after administration of EPO, and the rate of blood transfusion were analyzed.

TABLE 1:Exclusion criteria for treatment with recombinant human erythropoietin.

Allergy to epoetin alpha

Significant bleeding or hemolysis

Uncontrolled hypertension

Acute infection or medical disease

Cardiovascular or blood disease

Need for concomitant administration of medication that may suppress erythropoiesis (eg, cytotoxic agents)

Patients in whom adequate antithrombotic prophylaxis cannot be performed


TABLE 2 :Exclusion criteria used by Salido8.


Prior anticoagulant treatment

Chronic hematological or liver disease

Postoperative hemorrhagic complications not attributable to surgery

Patients who were transfused with a postoperative hemoglobin >8.5 g/dl

TABLE 3 : Demographic data 




Number of patients



Mean age

69 years (range 30-85)

71 years (range 67-75)

Knee prosthesis



Hip prosthesis



Mean preoperative Hb* (g/dl)

12.3 (range 10.2-13)

12.4 (range 12.2-12.8)

Mean Hb on admission (g/dl)**

14.3 (range 11.3-15.9)

14.6 (range 13.9-15.3)

Mean postoperative Hb (g/dl)***

11.3 (range 8.4-13.5)

11.6 (range 11.6-11.6)



 *Mean preoperative Hb = mean Hb of the patients before starting treatment with EPO.

**Mean Hb on admission=mean Hb 24 hours before surgery.

***Mean post-operative Hb = mean Hb at 12 hours following surgery

Results :

A total of 61 patients were studied (Table 3), 44 with total knee prostheses (TKP) and 17 with total hip prostheses (THP). Mean age was 70 years (range 30-85). There were 58 women and 3 men. The affected side was the right in 32 and the left in 29. The femoral component was cemented in 6 and the tibial component in 39 of the TKP, while all the THP were cementless. Initial mean preoperative hemoglobin (Hb) was 12.3 g/dl (range 10.2-13). Mean Hb after administering 3 doses of EPO rose to 14.3 g/dl (range 11.3-15.9). Forty-one patients (67.2%) received a fourth dose of EPO on admission. Mean postoperative Hb, measured 12 hours after the procedure, decreased to 11.4 (range 8.5-13.5). Three patients (4.9%) were transfused, 2 undergoing TKP and 1 THP, with Hb of 8.4, 7.7 and 8.2 g/dl, respectively. Iron supplements were well tolerated in all patients and of the possible complications where EPO can act as a risk factor, there was only 1 case of postoperative deep venous thrombosis (1.6%) confirmed by echo-Doppler.


There is a current consensus that preoperative Hb levels are a predictive factor for the need for blood transfusion after primary hip and knee arthroplasty.8-14 . Salido8 reported that 69% of patients with a preoperative Hb level less than 13 g/dl were transfused and that they had 4 times greater risk of blood transfusion than those with a preoperative Hb level between 13-15 g/dl and 15.3 times greater risk than those with a Hb level greater than 15 g/dl.

          These conclusions, together with the already known risks of blood transfusion, 2, 4,8, 15,16 have led to attempts to minimize this problem through the use of measures such as blood recovery, controlled hypotension,4 fibrin spray,17 aprotinin,18  and particularly autologous blood donation and EPO,19 the latter two sometimes used in combination, among others.

Autologous blood donation has been and is one of the most widely used alternatives both in orthopedic surgery3,16,20-22 and other types of surgery that involve large blood losses such as thoracic or cardiac surgery,23 etc. However, we consider that though autologous donation removes the risk of transmission of contagious diseases its use is associated with other negative factors such as a greater number of transfusions,4,20 which, although less than with allogenic blood transfusion,21 is not free of risks, such as immunosuppression and increased risk of infection, and generating a longer hospital stay.4,23,24 Cohen20 reported that surgeons tended to transfuse patients included in autologous blood programs earlier and more frequently, and not only this, but also the waste of resources it implies in those cases where the blood is finally not used.4,15 Bierbaum15 reported that up to 45% of autologous blood was not used. On the other hand, patient donating autologous blood suffer a decrease in Hb prior to surgery,20 which also increases the likelihood of transfusion. In addition, some patients with low baseline Hb levels cannot be included in autologous blood programs, and others may have anemia, medical problems or a poor response to erythropoietin.19 It is for this that some surgeons19,24 tend to favor the combined use of autologous blood donation and EPO, arguing that in this way the need for allogenic blood transfusion is reduced.

Our results with the use of EPO (4.9% rate of blood transfusion in patients with a preoperative Hb <13 g/dl) versus those obtained in our department without EPO8 (69% rate of blood transfusion in patients with a preoperative Hb <13 g/dl), though both samples are not comparable for several reasons (one prospective and another retrospective, added inclusion/exclusion criteria of EPO, higher number of cemented tibial components, different model in hip prosthesis, and a higher prevalence of the female sex attributable in part to several factors25,26) are agree with the effectiveness of EPO treatment shown by other authors such as Pierson,27 who reported that the rate of blood transfusion was 2.1% in the group of patients treated with EPO versus 16.4% in untreated patients.

In addition, based on the studies by Cheung28 and Golberg29,  we consider that the weekly dose is as effective as the daily dose. On the other hand, the weekly use of a standard weight-independent dose of 40,000 IU, that would correspond to the “high dose” used by Feagan7 , provides more advantages than a dose adjusted for weight30 as it simplifies the treatment and no significant complications were observed (only one case of venous thrombosis). We also advocate the administration of a fourth dose of EPO in the immediate pre-operative period to patients with Hb levels <15 g/dl, based on the experience of other authors such as Andrade31 and on pharmacodynamic studies 28,32.

In conclusion, we think that use of EPO alone for transfusion prophylaxis in prosthetic hip and knee surgery is effective and efficient, has a low complexity of use and a low rate of complications.

Reference :

1. Liu T.K, Chen S.H. Simultaneous bilateral total knee arthroplasty in a single procedure. Intern Orthop. 1998;22:390-393.

2. Greenburg A.G, Benefits and risks of blood transfusion in surgical patients. World J Surg. 1996;20:1189-1193.

3. Steinitz D, Harvey E.J, Leighton R.K, Petrie D.P. Is homologous blood transfusion a risk factor for infection alter hip replacement. Can J Anaesth. 2001;44:355-358.

4. Sparling E.A, Nelson C.L, Lavender R, Smith J. The use of erythropoietin in the management of Jehovah’s witnesses who have revision total hip arthroplasty. J Bone Joint Surg Am. 1996;78:1548-1552.

5. Lemos MJ, Healy WL. Bood transfusion in orthopaedic operations. J Bone Joint Surg Am. 1996;78:1260-70.

6. Keating EM, Meding JB, Faris PM, Ritter MA. Predictors of transfusion risk in elective knee surgery. Clin Orthop. 1998;357:50-9.

7. Feagan BG, Wong CJ, Kirkley A, Johnston DWC, Smith FC, Whitsitt P. Ann Intern Med. 2000;133:845-54.

8. Salido JA, Marín LA, Gómez LA, Zorrilla P, Martínez C. Preoperative Hemoglobin levels and the need for transfusion alter prosthetic hip and knee surgery. J Bone Joint Surg Am. 2002;84:216-220.

9. Keating E.M, Meding JB, Faris PM, Ritter MA. Predictors of transfusion risk in elective knee surgery. Clin Orthop. 1998;357:50-59.

10. Aderinto J, Brenkel I.J. Preoperative predictors of the requirement for blood transfusion following total hip replacement. J Bone Joint Surg Br. 2004;86:970-973.

11. Nuttall G.A, Horlocker T.T, Santrach P.J, Oliver W.C, Dekutoski M.B, Bryant S. Predictors of blood transfusions in spinal instrumentation and fusion surgery. Spine. 2000;25:596-601.

12. Rama-Maceiras P, Acción-Barral M, González-Vazquez M, Fernández-Rosado B, Diéguez-Fernández M, López-Vila I. Necesidades transfusionales durante el intra y postoperatorio inmediato de la artroplastia de cadera y rodilla. Incidencia y factores asociados. Rev Esp Anestesiol Reanim. 1999;46:445-452.

13. Larocque B.J, Gilbert K, Brien W.F. Prospective validation of a point score system for predicting blood transfusion following hip or knee replacement. Transfusion. 1998;38:932-937.

14. Larocque B.J, Gilbert K, Brien W.F. A point score system for predicting the likelihood of blood transfusión alter hip or knee arthroplasty. Transfusion. 1997;37:463-467.

15. Bierbaum B, Hill C, Callaghan J, Galante J, Rubash H, Tooms R, Welch R. An analysis of blood management in patients having a total hip or knee arthroplasty. J Bone Joint Surg Am. 1999;81:2-10.

16. Lorentz A, Schipplick M, Gmehlin U, Osswald P.M, Winter M. Präoperative eigenblutspende mit flüssiglagerung bei künstlichem gelenkersatz. Anaesthesist. 1989;38:480-489.

17. Levy O, Martinowitz U, Oran A, Tauber, Horoszowski H. The use of fibrin tissue adhesive to reduce blood loss and the need for blood transfusión alter total knee arthroplasty. J Bone Joint Surg Am. 1999;81:1580-1588.

18. López-Anglada E, Paz-Aparicio J, Bertrand D, Gosálbez J, Núńez-Batalla D, Paz-Jiménez J. Influencia de la aprotinina en el sangrado postoperatorio de la artroplastia total de rodilla. Rev Ortop Traumatol. 2005;49:421-428.

19. Aksoy M.C, Tokgozoglu A.M. Erythropoietin for autologous blood donation in total hip arthroplasty patients. Arch Orthop Trauma Surg. 2001;121:162-165.

20. Cohen JA, Brecher ME. Preoperative autologous blood donation: benefit or detriment? A mathematical analysis. Transfusion 1995;35:640-644.

21. Borghi B, Casati A. Incidence and risk factors for allogenic blood transfusion during major joint replacement using an integrated autotransfusion regimen. Eur J Anaesth. 2000;17:411-417.

22. Longjohn D.B, Dorr L.D, McPherson E.J. Blood management challenges in revision hip arthroplasty. Orthopedics. 1999;22(suppl 1):148-150.

23. Hardy J.F, Harel F, Bélisle S. Transfusions in patients undergoing cardiac surgery with autologous blood. Can J Anesth. 2000;47:705-711.

24. Cushner FD, Hawes T, Kessler D, Hill K, Scuderi GR. Orthopaedic-Induced Anemia. Clin Orthop. 2005;431:145-49.

25. Valdes AM, Oene MV, Hart DJ, Surdulescu GL, Loughlin J, Doherty M, Spector TD. Reproductible Genetic Associations Between Candidate Genes and Clinical Knee Osteoarthritis in Men and Women. Arthritis Rheum. 2006;54:533-39.

26. Kurtz S, Mowat F, Ong K, Chan N, Lau E, Halpern M. Prevalence of Primary and Revision Total Hip and Knee Arthroplasty in the United States From 1990 Through 2002. J.Bone Joint Surg. Am. 2005;87:1487-97.

27. Pierson J.L, Hannon T.J, Earles D.R. A blood-conservation algorithm to reduce blood transfusions after total hip and knee arthroplasty. J Bone Joint Surg Am. 2004;86:1512-1518.

28. Cheung WK, Goon BL, Guilfoyle MC, Wacholtz MC. Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin after single and multiple subcutaneous doses to healthy subjects. Clin Pharmacokinet. 1998; 64:412-22.

29. Golberg MA, McCutchen JW, Jove M, Di Cesare P, Friedman RJ, Poss R, Guilfoyle M, Frei D, Young D. A safety and efficay comparison stdy of two dosing regimens of Epoetin Alfa in patients undergoing major Orthopaedic Surgery. Am J Orthop. 1996: 544-52.

30. Karkouti K, McCluskey SA, Evans L, Mahomed N, Ghannam M, Davey R. Erythropoietin is an effective clinical modality for reducing RBC transfusion in joint surgery. C J Anesth. 2005;52:362-68.

31. Andrade JR, Jove M, Landon G, Frei D, Guilfoyle M, Young D. Baseline hemoglobin as a predictor of risk of transfusion and response to epoetin alfa in Orthopedic Surgery patients. Am J Orthop. 1996: 533-42.

32. Ramakrishnan R, Cheun WK, Farrell F, Joffee L, Jusko WJ. Pharmacokinetic and Pharmacodynamic modeling of Recombinant Human Erythropoietin after intravenous and subcutaneous dose administration in cynomolgus monkeys. JPET. 2003; 306: 324-31.


This is a peer reviewed paper 

Please cite as : Luis A. Gómez-Navalón : Blood Transfusion In Primary Hip And Knee Arthroplasty. Preoperative Treatment With Recombinant Human Erythropoietin

J.Orthopaedics 2007;4(4)e5





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