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ORIGINAL RESEARCH |
From the Departments of Anesthesiology and Intensive Care, and Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden.
Address reprint requests to: Monica Hyllner, MD, Sahlgrenska University Hospital, Department of Anesthesiology and Intensive Care, Göteborg, SE-413 45, Sweden; E-mail: monica.hyllner{at}vgregion.se.
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ABSTRACT |
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METHODS: Forty-one women scheduled for radical hysterectomy were randomized to preoperative autologous blood donation with or without preoperative recombinant human erythropoietin therapy. All patients were scheduled to deposit three units of blood within 2 weeks before surgery. Hemoglobin, erythrocyte volume fraction, blood cells, iron status, and hemolysis were analyzed before and after surgery.
RESULTS: Hemoglobin levels decreased continuously in both groups after the first autologous donation until day 1 postoperatively. With erythropoietin therapy, the erythrocyte volume fraction and hemoglobin levels were significantly higher during precollection and day 1 after surgery. Preoperatively, the drop was 12 g/L less in the erythropoietin-treated group. The additional use of erythropoietin therapy reduced the inability of patients to predeposit blood from 17.8% to 3.4%.
CONCLUSION: Most women can predeposit three units of whole blood in only 2 weeks without obtaining severe anemia. By treating women with erythropoietin, one out of seven can be prevented from a hemoglobin level below the 100 g/L limit for donation.
Alternatives to conventional blood transfusion and perioperative blood management such as preoperative autologous blood collection and human recombinant erythropoietin therapy are common today because of patients’ concerns about disease transmission. Allogeneic blood transfusion has been in use for at least a century but is still associated with well-recognized, inherent, and unavoidable risks, such as infectious disease transmission and adverse immunologic reactions.1,2 Emerging infections constitute another risk, and the accessibility of stored blood is sometimes limited. An immunosuppressive effect of allogeneic blood transfusion has been demonstrated in several studies. For patients with cancer and trauma, immunosuppression may be detrimental. An increase in postoperative infection rates as well as cancer recurrence and shortened survival occurs after allogeneic blood transfusion compared with patients without transfusion or transfused with autologous blood.3–6 A single unit of transfused allogeneic blood has been associated with an increased risk of postoperative infections.7
Preoperative blood collection for autologous transfusion has become an established alternative to traditional allogeneic blood transfusion. Collection of autologous blood is usually performed once a week and starts 3–5 weeks before the scheduled surgery.8,9 In cancer surgery, there is usually limited time available for this program not to delay surgery, and collection has to be performed more rapidly. Radical hysterectomy due to cervical carcinoma is associated with a considerable blood loss and a need for blood transfusion. The mean blood loss has historically been reported to be 1500 mL but seems to be decreasing.10 A limiting factor for the volume of blood donated is the mild anemia that develops with only a moderate increase in erythropoiesis and erythropoietin production.11,12 The additional use of erythropoietin therapy in preoperative autologous blood collection programs has been shown to make the collection of blood more efficient, the volume of blood donated increased, and to maintain a higher hematocrit at the time of surgery.8,9
This study was performed to investigate whether preoperative treatment with erythropoietin facilitates the preoperative collection of autologous blood in a short period of time.
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MATERIALS AND METHODS |
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The specific sequence at each donation visit was phlebotomy for measuring hematologic parameters, phlebotomy for deposition of blood, followed by erythropoietin administration and crystalloid infusion. Erythropoietin was administered intravenously by a nurse at the three visits for blood donation. The other 7 days the patients themselves administered the erythropoietin subcutaneously, according to written instructions. No erythropoietin was given postoperatively. All patients received oral iron supplementation with 2 mg Fe++per kg of body weight daily before the surgery.
Peripheral venous blood samples were obtained before blood collection at the preoperative visits. In the erythropoietin group, samples were also taken 10 minutes after intravenous erythropoietin administration. Furthermore, samples were taken preoperatively the day before surgery or the same day, 1 hour after surgery, on day 1 after surgery, on day 5 (days 4–6), and finally at week 5 after surgery. Analyses were performed of blood concentrations of folates, hemoglobin, leukocytes, platelets, erythrocyte volume fraction (equivalent to hematocrit), and reticulocytes. Serum concentrations of folates, vitamin B12, bilirubin, ferritin, haptoglobin, iron, and total iron-binding capacity were measured by standard methods used for clinical purposes at the Department of Clinical Chemistry. The hematologic parameters were analyzed with Technicon H3 equipment (Bayer Diagnostics, Tarrytown, NY).
All patients received the same type of general anesthesia during surgery, and all patients were transfused with one to three units of autologous whole blood. Almost all transfusions were given intraoperatively when the hemoglobin level decreased to less than 85 g/L or if the patient showed clinical signs of hypovolemia. The surgeons and anesthesiologists responsible for the individual patients were blinded to whether patients had received erythropoietin or not in connection with predeposition of blood. Measurement of aspirated blood volume and the weight of sponges used during surgery were used to estimate blood loss.
The values are given as medians and 25–75 percentiles or range. The Mann-Whitney test, two-tailed, was used for all comparisons between the groups. Differences were considered significant at P < .05. The left tail (below 125 g/L) of hemoglobin distribution was assumed to coincide with a normal distribution. The maximum likelihood estimate of the mean and standard deviation of that distribution was determined by a special program (Anders Odén, Kungälv, Sweden).
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RESULTS |
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All 37 patients required autologous blood transfusion intraoperatively. Two patients in the control group received one unit of whole blood, three patients received two units, and ten patients received three units. In the erythropoietin group, one patient received one unit, nine patients received two units, and five patients received three units. Forty-six units of blood were reinfused in the erythropoietin group, and 47 units were used in the control group. Eighteen out of 111 units of autologous blood were not transfused. Autologous blood was sufficient for transfusion for 30 patients. Another seven patients managed to predeposit three autologous units but also received additional allogeneic transfusions intraoperatively. The erythropoietin therapy was well tolerated by all patients, and there were no systemic side effects or allergic reactions reported.
The erythrocyte volume fraction and hemoglobin median concentrations dropped during precollection in both groups, significantly less in the erythropoietin group (Figure 1, P < .001). Hemoglobin levels decreased continuously in both groups after the first autologous donation until day 1 postoperatively, after which the levels increased again. At the time of surgery, there was no difference between the groups, but on postoperative day 1, there was a significant difference (P < .05), with the highest hemoglobin value in the erythropoietin group. On postoperative day 5 and after 5 weeks, there was no longer any significant difference between the two groups. The reticulocyte count increased in both groups during autologous donation, but earlier and to significantly higher values in the erythropoietin group (Figure 2). The highest median level in the erythropoietin group, 6.6%, was found 1 week before surgery and was significantly higher than in the control group (P < .001). The highest level in the control group, 5.7%, was reached day 1 after surgery. Five weeks after surgery the levels in both groups were back to baseline values. There was a slight reactive increase of platelet and leukocyte concentrations postoperatively, but they were still within reference values, with no significant differences between the two groups (Table 2).
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. The postoperative decrease in serum iron concentration was more pronounced in the erythropoietin group than in the control group. The iron concentration at the first visit was significantly lower in the control group, but still within the reference range. The ferritin concentration was significantly lower in the control group than in the erythropoietin group postoperatively, but within the reference range. However, the ferritin values were lower 5 weeks after surgery compared with preoperative values. No significant difference in total iron-binding capacity concentration between the groups was found. The median bilirubin and haptoglobin concentrations changed slightly but did not indicate significant hemolysis. There were no changes in vitamin B12 and folate concentrations.
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DISCUSSION |
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All patients received oral iron supplementation to facilitate erythropoiesis. In patients receiving erythropoietin treatment, the serum iron concentrations decreased more rapidly. Vitamin B12 and folates are necessary for all replication and differentiation. The levels were normal in both groups throughout the study and were not a limiting factor for restoring the hemoglobin values.
Postoperatively, the hemoglobin levels recovered rapidly, and on day 5 after surgery, there was no difference between the two groups. The rapidly corrected anemia in the control group may be explained by accelerated endogenous erythropoietin production in the postoperative period, induced by repeated donations.13 In patients donating blood before elective orthopedic surgery, Tasaki et al14 demonstrated a more rapid recovery from anemia in untreated patients than might have been expected.
This study did not evaluate whether predeposit per se is of benefit in reducing the risk for allogeneic blood transfusion. Of 37 patients who predeposited three units of blood, seven received allogeneic blood in addition to the predeposited blood. Eighteen units of predeposited blood were not reinfused. This seems reasonable because a smaller amount deposited would result in a larger percentage of patients receiving allogeneic blood. On the other hand, more than three units predeposited would most likely result in even more units not reinfused. This assumes that some red blood cells result from an additional erythropoiesis secondary to blood predeposit 2 weeks before surgery. Preoperative autologous blood donation could prevent exposure to allogeneic blood for most patients.15–17 An important question is whether two or three units should be predeposited. The mean blood loss for this procedure has been reported earlier to be 1500 mL, a loss corresponding to about three units of blood.10 As many as 22 of 37 patients needed all their units for transfusion, 72% of the patients in the control group and 47% in the erythropoietin group.
Autologous transfusion is beneficial to patients scheduled for elective surgery, and preoperative autologous donation programs can minimize the exposure to allogeneic blood transfusion in cancer surgery. In this study, three units of whole blood were collected in only 2 weeks without adverse effects. Subcutaneous recombinant human erythropoietin treatment may be useful in a sub-population of patients who are anemic at the first visit for blood collection.
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Footnotes |
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Received May 15, 2001. Received in revised form November 20, 2001. Accepted November 29, 2001.
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REFERENCES |
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2. Beauregard P, Blajchman MA. Hemolytic and pseudohemolytic transfusion reactions: An overview of the hemolytic transfusion reactions and the clinical conditions that mimic them. Transfus Med Rev 1994;8:184–99.[Medline]
3. Blumberg N, Agarwal MM, Chuang C. Relation between recurrence of cancer of the colon and blood transfusion. Br Med J (Clin Res Ed) 1985;290:1037–9.
4. Tartter PI, Quintero S, Barron DM. Perioperative blood transfusion associated with infectious complications after colorectal cancer operations. Am J Surg 1986;152:479–82.[Medline]
5. Blumberg N, Agarwal MM, Chuang C. A possible association between survival time and transfusion in cervical cancer. Yale J Biol Med 1988;61:493–500.[Medline]
6. Eisenkop SM, Spirtos NM, Montag TW, Moossazadeh J, Warren P, Hendrickson M. The clinical significance of blood transfusion at the time of radical hysterectomy. Obstet Gynecol 1990;76:110–3.
7. Vignali A, Braga M, Gianotti L, Radaelli G, Gentilini O, Russo A, et al. A single unit of transfused allogeneic blood increases postoperative infections. Vox Sang 1996;71: 170–5.[Medline]
8. Mercuriali F, Zanella A, Barosi G, Inghilleri G, Biffi E, Vinci A, et al. Use of erythropoietin to increase the volume of autologous blood donated by orthopedic patients. Transfusion 1993;33:55–60.[Medline]
9. Goodnough LT, Rudnick S, Price TH, Ballas SK, Collins ML, Crowley JP, et al. Increased preoperative collection of autologous blood with recombinant human erythropoietin therapy. N Engl J Med 1989;321:1163–8.[Abstract]
10. Benjamin I, Barakat RR, Curtin JP, Jones WB, Lewis JL, Hoskins WJ. Blood transfusion for radical hysterectomy before and after the discovery of transfusion-related human immunodeficiency virus infection. Obstet Gynecol 1994;84:974–8.
11. Lorentz A, Jendrissek A, Eckardt KU, Schipplick M, Osswald PM, Kurtz A. Serial immunoreactive erythropoietin levels in autologous blood donors. Transfusion 1991;31: 650–4.[Medline]
12. Kickler TS, Spivak JL. Effect of repeated whole blood donations on serum immunoreactive erythropoietin levels in autologous donors. JAMA 1988;260:65–7.[Abstract]
13. Levine E, Rosen A, Sehgal L, Gould S, Sehgal H, Moss G. Accelerated erythropoiesis: The hidden benefit of autologous donation. Transfusion 1990;30:295–7.[Medline]
14. Tasaki T, Ohto H, Hashimoto C, Abe R, Saitoh A, Kikuchi S. Recombinant human erythropoietin for autologous blood donation: Effects on perioperative red-blood-cell and serum erythropoietin production. Lancet 1992;339: 773–5.[Medline]
15. Biesma DH, Marx JJM, Kraaijenhagen RJ, Franke W, Messinger D, van de Wiel A. Lower homologous blood requirement in autologous blood donors after treatment with recombinant human erythropoietin. Lancet 1994; 344:367–70.[Medline]
16. Pinkerton PH, Covens A. Autologous blood transfusion in radical hysterectomy. Transfus Med 1996;6:223–5.[Medline]
17. Pellegrino A, Landoni F, Cormio G, Ferrando P, Lissoni A, Scalambrino S, et al. Effectiveness of autologous blood transfusion in patients undergoing radical hysterectomy. Ann Chir Gynaecol 1995;84:391–4.[Medline]
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) groups during the pre-and postoperative follow-up. The 25–75 percentiles are also given. For differences between the groups: *P < .05, **P < .01, ***P < .001.