Anemia is common in cancer patients. The pathophysiology is multifactorial, however the most common cause is the anemia of chronic diseases (ACD). In 20-50% of cancer patients, anemia restricts physical activity and quality of life and requires transfusion support. The percentage of patients necessitating transfusion dramatically increases when patients require surgery.
The traditional belief that blood transfusion is an effective and safe therapy has been challenged by a heightened awareness of the infectious and immunologic risks associated with allogeneic blood administration. In cancer patients transfusion-induced immunomodulation may have the potential to significantly increase postoperative infections and cancer recurrence so that it seems reasonable to minimize allogeneic blood exposure.
Several strategies have been adopted to reduce allogeneic transfusion in surgical patients, however to properly select the appropriate blood conservation strategies the blood transfusion requirements for each patient should be defined.
Allogeneic blood transfusion in surgery can be reduced by the introduction of autologous blood (AB) programmes and by the use of rHuEPO, alone or in association with AB techniques. AB donation is currently a standard of care for elective surgical patients but its efficacy is limited by anemia that prevents the donation of the optimal number of AB units. rHuEPO has been shown to significantly increase the volume of AB that anemic patients can predeposit or, used perisurgically, to expand the circulating RBCs mass before surgery. Moreover clinical trials employed rHuEPO in anemic cancer patients with various solid tumors both on and off chemotherapy reporting a significantly increase in Hct in more than 50% of the treated patients. Recently different studies have shown the efficacy of rHuEPO in increasing the volume of AB also in patients with ACD and cancer, thus proving to be a useful addition to existing strategies of blood conservation to minimize exposure to allogeneic blood in surgical cancer patients.
AbelsR.I., LarholtK.M., KrantzK.D., BryantE.C.: Recombinant human erythropoietin (r-HuEPO) for the treatment of the anemia of cancer. In: Blood Cell Growth Factors: Their present and future in Hematology and Oncology.MurphyM.J. (Ed.), pp. 121–141, Alpha Med Press, Dayton, OH, 1992.
2.
American College of Physicians: Practice strategies for elective red blood cell transfusion. Ann. Intern. Med., 116: 403–406, 1992.
3.
AsanoY., OkamuraS., ShibuyaT., HaradaM., NihoY.: Growth of clonogenic myeloblastic leukemia cells in the presence of human recombinant erythropoietin in addition to various human recombinant hemopoietic growth factors. Blood, 72: 1382–1386, 1988.
4.
BerdelW.E., OberbergD., ReufiiB., ThielE.: Studies on the role of recombinant human erythropoietin in growth regulation of human nonhematopoietic tumor cells in vitro. Ann. Hematol., 63: 5, 1991.
5.
BirgegardG., WideL., SimonsonB.: Marked erythropoietin increase before fall in Hb after treatment with cytostatic drugs suggests mechanism other than anemia for stimulation. Br. J. Haematol., 72: 564–566, 1989.
6.
BlairS.D., JanvrinS.B.: Relation between cancer of the colon and blood transfusion. Br. Med. J., 290: 1516–1517, 1985.
7.
BlumbergN.: Allogeneic transfusion and infections: economic and clinical implications. Sem. Hematol., 34 (suppl 2): 34–40, 1997.
8.
BlumbergN., AgarwalM., ChuangC.: Relation between recurrence of cancer of the colon and blood transfusion. Br. Med. J., 290: 1037–1039, 1985.
9.
BlumbergN., HealJ.M.: Effects of transfusion on immune function. Cancer recurrence and infection. Arch. Pathol. Lab. Med., 118: 371–379, 1994.
10.
BlumbergN., HealJ.M.: Transfusion and host defenses against cancer recurrence and infection. Transfus.29: 236–245, 1989.
11.
BlumbergN., HealJ.M.: Transfusion-induced immunomodulation and its possible role in cancer recurrence and perioperative bacterial infection. Yale J. Biol. Med., 63: 429–433, 1990.
12.
BrecherM.E., RosenfeldM.: Mathematical and computer modeling of acute normovolemic hemodilution. Transfus., 34: 176–179, 1994.
13.
BukowskiR.M.: Clinical efficacy of recombinant human erythropoietin (r-HuEPO) in the treatment of anemia associated with cancer. Erythropoiesis, 5: 108–114, 1994.
14.
BunnP.A., RidgwayE.C.: Hematologic manifestations of malignancy. In: Cancer, DevitaV.T. (Eds.), 3rd ed., p. 1917, JB Lippincott, Philadelphia, 1989.
15.
BurrowsL., TartterP.: Effect of blood transfusion on colonic malignancy recurrent rate. Lancet, ii: 662, 1982.
16.
BuschM.P., LeeT.H., HeitmanJ.: Allogeneic lymphocytes but not therapeutic blood elements induce reactivation and dissemination of latent human immunodeficiency virus type 1 infection: implications for transfusion support of infected patients. Blood, 1992; 80: 2128–2135.
17.
BuschO.R., HopW.C.J., Hoynck van PapendrechtM.A.W., MarquetR.L., JeekelJ.: Blood transfusion and prognosis in colorectal cancer. N. Engl. J. Med., 328: 1372–1376, 1993.
18.
BuschO.R., Hoynck van PapendrechtM.A.W., MarquetR.L., JeekelJ.: Experimental and clinical results of perioperative treatment with recombinant human erythropoietin. In: Pathophysiology and pharmacology of erythropoietin.PagelH., WeissC., JelkmannW. (Eds.), Springer Verlag, Berlin, Germany, pp. 315–320, 1992.
19.
Canadian Orthopedic Perioperative Erythropoietin Study Group.Effectiveness of perioperative recombinant human erythropoietin in elective hip replacement. Lancet, 341: 1227–1232, 1993.
20.
CaseD.C.Jr., SearsD.A.: Anemia of chronic disease: spectrum of associated diseases in a series of unselected hospitalized patients. Am. J. Med., 87: 639–646, 1989.
21.
CazzolaM., MercurialiF., BrugnaraC.: Use of recombinant human erythropoietin outside the setting of uremia. Blood, 89: 4248–4267, 1997.
22.
Centers for Disease Control.Update. Yersinia enterocolitica bacteremia and endotoxin shock associated with red blood cell transfusions: United States 1991. JAMA, 265: 2174–2175, 1991.
23.
Consensus Conference: Blood Management Surgical Practice Guidelines. Am. J. Surg., 170 (6A suppl. 1), 1S–73S, 1995.
24.
CooleyD.A.: Conservation of blood during cardiovascular surgery. Am. J. Surg., 170, n°6A (suppl.): 53S–59S, 1995.
25.
CreasyT.S., VeitchP.S., BellP.R.: A relationship between perioperative blood transfusion and recurrence of carcinoma of the sigmoid colon following potentially curative surgery. Ann. R. Coll. Surg. Engl., 69: 100–103, 1987.
26.
DainiakN., KulkarniV., HowardD., KalmantiM., DeweyM.C., HoffmanR.: Mechanisms of abnormal erythropoiesis in malignancy. Cancer, 51: 1101, 1983.
27.
DeGowinR.L., GibsonD.P.: Erythropoietin and the anemia of mice bearing extramedullary tumor. J. Lab. Clin. Med., 94: 303, 1979.
FisherJ.W., RohB.L.: Influence of alkylating agents on kidney erythropoietin production. Cancer Res., 24: 983–988, 1964.
32.
FrankishP.D., McNeeR.K., AlleyP.G., WoodfieldD.G.: Relation between cancer of colon and blood transfusion. (Letter.) Br. Med. J., 290(6484): 1827, 1985.
33.
FriedmanB.A., ObermanH.A., ChadwickA.R., KingdonK.I.: The maximum surgical blood order schedule and surgical blood use in the United States. Transfus., 16: 380–387, 1976.
34.
GasconP., ZoumbosN.C., YoungN.S.: Immunological abnormalities in patients receiving multiple blood transfusions. Ann. Intern. Med., 100: 173–177, 1984.
GillonJ.: Controversies in transfusion medicine. Acute normovolemic hemodilution in elective major surgery. Transfus., 34: 269–271, 1994.
37.
GoodnoughL.T., RudnickS., PriceT.H., BallasS.K., CollinsM.L., CrowleyJ.P., KosminM., KruskallM.S., LenesB.A., MenitoveJ.E., SilbersteinL.E., SmitK.J., WallasC.H., AbelsR., Von TressM.: Increased preoperative collection of autologous blood with recombinant human erythropoietin therapy N. Engl. J. Med., 321: 1163–1168, 1989.
38.
GoodnoughL.T., AndersonK.C., KurtzS., LaneT.A., PisciottoP.T., SayersM.H., SilberteinL.E.: Indications and guidelines for the use of hematopoietic growth factors. Transfus., 33: 944–959, 1993.
39.
GoodnoughL.T., BrittenhamG.M.: Limitations of the erythropoietic response to serial phlebotomy: Implications for autologous blood donor programs. J. Lab. Clin. Med., 115: 28–35, 1990.
40.
GoodnoughL.T., ShuckJ.M.: Risks, options and informed consent for blood transfusion in elective surgery. Am. J. Surg., 59: 602–607, 1990.
41.
HansenE., AltmeppenJ., KutzN., PrasserC., TaegerK.: Praxis der intraoperativen Autotransfusion mit Bestrahlung in der Tumorchirurgie. In: Aktuelles zur Eigenbluttransfusion, MempelW., MempelM., EndersW. (Eds.), pp. 54–60, Sympomed, Munken, 1997.
42.
HansenE., WolffN., KnuechelR., RuschoffJ., HofstaedterF., TaegerK.: Tumor cells in blood shed from the surgical field. Arch. Surg., 130: 387–393, 1995.
43.
HebertP.C., HuL.Q., BiroG.P.: Review of physiologic mechanisms in response to anemia. Can. Med. Assoc. J., 157 (11 Suppl): S27–S40, 1997.
44.
HeissM.M., MempelW., JauchK.W., DelanoffC., MayerG., MempelM., EissnerH.J., SchildbergF.W.: Beneficial effect of autologous blood transfusion on infectious complications after colorectal cancer surgery. Lancet, 342: 1328–1333, 1993.
45.
HeissM.M., MempelW., DelanoffC., JauchK.W., GabkaG., MempelM., DieterichH.J.: Blood transfusion modulated tumor recurrence: first results of randomized study of autologous versus allogeneic blood transfusion in colorectal cancer surgery. J. Clin. Oncol., 12: 1859–1867, 1994.
46.
HoubiersJ.G., BrandA., van de WateringL.M., HermansJ., VerweyP.J., BijnenA.B., PahlplatzP., Eeftinck SchattenkerkM., WobbesT., de VriesJ.E.: Randomized controlled trial comparing transfusion of leucocyte-depleted or buffy-coat depleted blood in surgery for colorectal cancer. Lancet, 344: 573–578, 1994.
47.
JeekelJ.: Autologous blood donation and epoetin alfa in cancer surgery. Semin. Hematol., 33 (suppl. 2): 43–7, 1996.
48.
KaplanJ., SarniakS., GitlinJ.: Diminished helper: suppressor lymphocyte ratios and natural killer cell activity in recipients of repeated blood transfusions. Blood, 64: 308–310, 1984.
49.
KennedyS., KamineJ., MarkovitzD., FenrickR., PaganoJ.: An Epstein-Barr virus immediate-early gene product trans-activates gene expression from the human immunodeficiency virus long terminal repeat. Proc. Natl. Acad. Sci. USA, 85: 1652–1656, 1988.
50.
KettelhackC., HonesC., MessingerD., SchlagP.M.: Randomized multicentre trial of the influence of recombinant human erythropoietin on intraoperative and postoperative transfusion need in anemic patients undergoing right hemicolectomy for carcinoma. Br. J. Surg., 85(1): 63–67, 1998.
51.
KicklerT.S., SpivakJ.L.: Effect of repeated whole blood donations on serum immunoreactive erythropoietin levels in autologous donors. JAMA, 260: 65–67, 1988.
52.
KirchhoffL.V.: Is Trypanosoma cruzi a new threat to our blood supply? Ann. Intern. Med., 111: 773–775, 1989.
53.
KleinH.G.: Immunomodulation caused by blood transfusion. In: Clinical practice of transfusion medicine, PetzL.D., SwisherS.N., KleinmanS., SpenceR.K., StraussR.G. (Eds.), pp. 59–65, Churchill Livingstone Inc, New York, 1996.
54.
KonishiT., KanekoT., OhbayashiT., OnkiT., SaitopuY., YamatoY.: Effectiveness or erythropoietin for cardiovascular surgery to prevent homologous blood transfusions. Journal of the Japanese Association for Thoracic Surgery, 41: 187–192, 1993.
55.
KruskallM.S., YomtovianR., DzikW.H., FriedmanK.D., UmlasJ.: On improving the cost-effectiveness of autologous blood transfusion practices. Transfus., 34: 259–264, 1994.
56.
KulierA.H., GombotzH., FuchsG., VuckovicU., MetzlerH.: Subcutaneous recombinant human erythropoietin and autologous blood donation before coronary artery bypass surgery. Anesth. analg., 76(1): 102–106, 1993.
57.
LeeG.: The anemia of chronic disease. Semin. Hematol., 20: 61–80, 1983.
LudwigH., FritzE., LeitgebC., KrainerM., KuhrerI., SagasterP., UmekH.: Erythropoietin treatment for chronic anemia of selected hematological malignancies and solid tumors. Ann. Oncol., 4: 161–167, 1993.
60.
MargolikJ.B., VolkmanD.J., FolksT.M., FauciA.S.: Amplification of HTLV-III/LAV infection by antigen-induced activation of T cells and direct suppression by virus of lynphocyte blastogenic responses. J. Immunol., 138: 1719–1723, 1987.
MercurialiF., BiffiE., InghilleriG., VinciA.: Low hematocrit: limiting factor in autologous blood predonation program. In: Transfusion in Europe, CastelliD., GenetetB., HabibiB., NyddegerY., (Eds.), pp. 291–298, Arnette SA Paris ISBT, Paris, 1989.
63.
MercurialiF., InghilleriG., BiffiE., ColottiM.T.: Short-term, low dose recombinant human erythropoietin administration in surgery. Br. J. Anaesth., 78(suppl. 1): 64, 1997.
64.
MercurialiF., InghilleriG.: Proposal of an algorithm to help the choice of the best transfusion strategy. Curr. Med. Res. Opin., 13, No8: 465–478, 1996.
65.
MercurialiF., GualtieriG., SinigalliaL., InghilleriG., BiffiE., VinciA., ColottiM.T., BarosiG., Lambertenghi DeliliersG.: Use of recombinant human erythropoietin to assist autologous blood donation by anemic reumathoid arthritis patients undergoing major orthopedic surgery. Transfus., 34: 501–506, 1994.
66.
MercurialiF., ZanellaA., BarosiG., InghilleriG., BiffiE., VinciA., ColottiM.T.: Use of erythropoietin to increase the volume of autologous blood donated by orthopedic patients. Transfus., 33: 55–60, 1993.
67.
MessmerK., Sunder-PlassmanL., KlovekornW.P., MendlerN., HolperK.: Circulatory significance of hemodilution: rheological changes and limitations. Adv. Microcirc., 1972:4: 1–77.
68.
MillerC.B., JonesR.J., PiantadosiS., AbeloffM.D., SpivakJ.L.: Decreased erythropoietin response in patients with the anemia of cancer. N. Engl. J. Med., 322: 1689–1692, 1990.
69.
MillerC.B., PlataniasL.C., MillsS.R., ZahurakM.L., RatainM.J., EttingerD.S., JonesR.J.: Phase I-II trial of erythropoietin in the treatment of cisplatin-associated anemia. J. Nat. Cancer Inst., 84: 98–103, 1992.
70.
MonkT.: Improving the outcome of acute normovolemic hemodilution with epoetin alfa. Semin. Hematol., 33(suppl. 2): 48–50, 1997.
71.
MonkT.G., GoodnoughL.T., BirkmeyerJ.D., BrecherM.E., CatalonaW.J.: Acute normovolemic hemodilution is a cost-effective alternative to preoperative autologous blood donation by patients undergoing radical retropubic prostatectomy. Transfus., 35: 559–565, 1995.
72.
MurrayJ.F., EscobarE., RappaportE.: Effects of blood viscosity on hemodynamic responses in acute normovolemic anemia. Ann. J. Physiol., 216: 638–642, 1969.
73.
National Heart, Lung and Blood Institute Panel on the use of Autologous Blood. Transfusion alert: use of autologous blood. Transfus., 35: 703–711, 1995.
74.
National Institutes of Health Consensus Conference: Perioperative red blood cell transfusion. JAMA, 260: 2700–2703, 1988.
75.
NelsonC.L., FontenotH.J.: Ten strategies to reduce blood loss in orthopedic surgery. Am. J. Surg., 170, n° 6A(suppl.): 64S–68S, 1995.
76.
NessP.M., WalshP.C., ZahurakM., BaldwinM., PiantadosiS.: Prostate cancer recurrence in radical surgery patients receiving autologous or homologous blood. Transfus., 32: 31–36, 1992.
77.
OpelzG., SengarD.P., MickeyM.R., TerasakiP.I.: Effect of blood transfusion on subsequent kidney transplants. Transplant. Proc., 5: 253–259, 1973.
78.
PlataniasL.C., MillerC.B., MickR., HartR.D., OzerH., McEvillyJ.M., JonesR.J., RatainM.J.: Treatment of chemotherapy-induced anemia with recombinant human erythropoietin in cancer patients. J. Clin. Oncol., 9: 2021–2026, 1991.
79.
PolkH.C.Jr., GeorgeC.D., WelhausenS.R., CostK., DavidsonP.R., ReganM.P., BorzottaA.P.: A systematic study of host defense processes in badly injured patients. Ann. Surg., 204: 282–299, 1986.
80.
ReissmanK.R., UdupaK.B.: Effect of erythropoietin on proliferation of erythropoietin-responsive cells. Cell Tissue Kinet., 5: 481–487, 1972.
81.
RodmanT., CloseH.P., PurcellM.K.: The oxyhemoglobin dissociation curve in anemia. Ann. Intern. Med., 52: 295–309, 1960.
82.
RoseE., RaiK., RevickiD.: Clinical and health status assessment in anemic chronic lymphocytic leukemia (LCC) patients treated with epoetin alfa (EPO) [Abstract 209]. Blood, 84(Suppl. 1): 526a, 1994.
83.
RutherfordC.J., KaplanH.S.: Autologous blood donation - Can we bank on it? (Edit) N. Engl. J. Med., 332: 740–742, 1995.
84.
SazamaK.: Bacteria in blood for transfusion. Arch. Pathol. Lab. Med., 118: 350–364, 1994.
85.
SchreiberG.B., BuschM.P., KleinmanS.H., KorelitzJ.J.: The risk of transfusion-transmitted viral infections. N. Engl. J. Med., 334: 1685–1690, 1996.
86.
ShivdasaniR.A., AndersonK.C.: Graft-versus-host disease. In: Clinical practice of transfusion medicine, PetzL.D., SwisherS.N., KleinmanS., SpenceR.K., StraussR.G. (Eds.), pp. 931–46, Churchill Livingstone Inc, New York, NY, 1996.
87.
SilvergleidA.J.: Preoperative autologous donation: what we have learned. Transfus., 31: 99–100, 1991.
88.
SpenceK.S.: The status of bloodless surgery. Transf. Med. Rev., 5: 274–286, 1991.
89.
SpenceR.K.: Surgical red blood cell transfusion practice policies. Am. J. Surg., 170, n° 6A(suppl.): 3S–12S, 1995.
90.
SpivakJ.L.: Rationale for the use of recombinant human erythropoietin (r-HuEPO) in the management of anemic cancer patients. Erythropoiesis, 5: 101–107, 1994.
91.
SpivakJ.L.: Recombinat human erythropoietin and the anemia of cancer. Blood, 84: 997–1004, 1994.
TriulziD.J., VanekK., RyanD.H., BlumbergN.: A clinical and immunologic study of blood transfusion and postoperative infection in spinal surgery. Transfus., 32: 517–524, 1992.
98.
TumanK.J.: Tissue oxygen delivery: the physiology of anemia. Anaest. Clin. North. Am., 9: 451–469, 1990.
99.
UmlasJ., FosterS.A., DalaiS.A., O'LearyS.M., GarciaL., KruskallM.S.: Red cell loss following orthopedic surgery: the case against postoperative salvage. Transfus., 34: 402–406, 1994.
100.
Van AkenW.G.: Does perioperative blood transfusion promote tumor growth? Transfus. Med. Rev., 3: 243–252, 1989.
101.
Van CampB.: Anemia in cancer. Erythropoiesis, 2: 39–401991.
102.
Van RoodJ.J., ClaasF.H.: The influence of allogeneic cells on the human T and B cell repertoire. Science, 248: 1388–1393, 1990.
WeidenP.L., BeanM.A., SchulzP.: Perioperative blood transfusion does not increase the risk of colorectal cancer recurrence. Cancer, 60: 870–874, 1987.
105.
WeiskopfR.B.: Mathematical analysis of isovolemic hemodilution indicates that it can decrease the need for allogeneic blood transfusion. Transfus., 34: 37–41, 1994.
106.
WelchH.G., MeehanK.R., GoodnoughL.T.: Prudent strategies for elective red blood cell transfusion. Ann. Int. Med., 116: 393–402, 1992.
107.
WellsL., AlaF.A.: Malaria and blood transfusion. Lancet, i: 1317–1319, 1985.
108.
WidmannF.K., (Ed.): Standards for blood banks and transfusion services, pp. 1–56, 15th ed., American Association of Blood Banks, Bethesda, 1993.
109.
WoodP., NygaandS., HrusheskyW.J.M.: Cisplatin-induced anemia is correctable with erythropoietin. Blood, 72(Suppl.): 52, 1988.
