Review

0 1991 S. Karger AG. Basel Vox Sang 1991;61:81-83 0042-9007/9V0612-0081$2.75/0

Autologous Transfusion - Too Far, Too Soon?

J . Gillona, K. Bella, R . J . Prescottb

‘Scottish National Blood Transfusion Service, South-East Regional Centre and Department of Transfusion Medicine, Royal Infirmary, Edinburgh; bMedical Statistics Unit, University of Edinburgh, UK

For patients undergoing elective surgery, autologous transfusion is potentially the most useful of measures to reduce exposure to homologous blood. Serious adverse effects of blood transfusion are uncommon but continuing publicity about viral transmission, particularly HIV, has stimulated the adoption and expansion of autologous trans- fusion programmes. Are these developments in patients’ best interests?

Perioperative haemodilution, the withdrawal of 2 4 units of blood and simultaneous infusion of crystalloid and/or col- loid to maintain blood volume, may reduce transfusion re- quirements but necessitates careful assessment of the pa- tient’s cardiovascular and respiratory reserve, and is safest when invasive monitoring is used to ensure tissue oxygen- ation is not compromised [l, 21. Intraoperative salvage using modern, sophisticated machines has been shown to be safe and is of undoubted benefit in situations of massive haemor- rhage such as liver transplantation. When used in a variety of more routine surgical procedures, these machines have also been shown to reduce homologous blood requirements, but many studies have used historical controls and may have overestimated this effect [3-51. The effect on clinical out- come of both perioperative haemodilution and intraoper- ative autologous transfusion (IOAT) has not been adequate- ly researched and their cost-effectiveness is in doubt when rigorously screened homologous blood is plentiful [6].

For predeposit autologous transfusion, where the pa- tient donates blood during the immediate preoperative pe- riod for his or her own use, the situation is, on the face of it, more straightforward. Careful selection of patients and me- ticulous attention to detail in designing the system for ob- taining, storing and transfusing the autologous blood, as outlined in the Guidelines for Autologous Blood Trans-

fusion published by the Council of Europe [7] and the combined British Society for Haematology and British Blood Transfusion Society [8], should ensure that this pro- cedure is safe.

Yet several recently published papers suggest that some of the proponents of predeposit autologous transfusion may have become over-zealous in their attempts to abolish the need for homologous blood. Those engaged in research in this area - and those promoting such a system for routine use -must bear in mind the need to be certain that any risks inherent in the autologous donation and transfusion proce- dure do not outweigh the benefits of avoiding the risks of homologous blood.

The difficulty here is that the serious adverse effects of homologous transfusion are so uncommon. With highly sensitive tests being carried out on every donation, the risk of transfusion-transmitted HIV in the USA is estimated at between 1 in 30,000 and 1 in 150,000 per unit transfused [9], while in the UK the risk is estimated at between 1 in 330,000 and 1 in a million [lo]. Post-transfusion hepatitis B is now extremely rare while non-A, non-B hepatitis continues to be a problem in numerical terms, though up to date figures for the true incidence are not available. The picture is clouded also by doubt about the clinical importance of post-transfusion non-A, non-B hepatitis, and the risk will in any case be reduced by up to 80% when the enzyme immunoassay for antibodies to hepatitis C virus is intro- duced into routine use [ll].

It is obvious from these figures that any reduction in risks to patients will be difficult to measure. A corollary of this is that it will be equally difficult to determine if the rare adverse effects of the autotransfusion itself have increased the risks to patients instead of increasing safety.

82 Gillon/Bell/Prescott

The main risk associated with predeposit auto-donation is that a vasovagal reaction might lead to further complica- tions such as myocardial infarction or stroke. These serious complications are extremely rare in blood donors, reflect- ing the care with which donors are selected, but vasovagal and more minor reactions are quite common -from 1 to 3% in most studies [l2,13]. One way of assessing the potential for harm to autologous donors is to compare reaction rates with those of healthy (‘homologous’) blood donors.

McVay et al. [14] carried out such a study comparing the outcome of 2,091 autologous donations with that of 4,737 homologous donations. They concluded that ‘. . . autolo- gous donation, in general, is as safe as homologous dona- tion’. Yet they showed that the donors at greatest risk of a reaction were autologous donors who reacted at their first donation. Furthermore, in the two major age groups which they report (17-29 and 3 0 4 3 , after allowance for first-time or repeat donation, significantly higher reaction rates oc- curred in the autologous donors. This might be due to an unfavourable sex and weight distribution, as is implicitly implied by the author’s multivariate analysis of risk factors, but despite the reassuring conclusion of the authors, there is still considerable cause for concern. Autologous donors, even when selected with are, are likely to be older and less fit than normal blood donors. Despite the risk of adverse reactions decreasing with age [14], increase in the risk of myocardial infarction, for instance, might occur, yet only become apparent after many thousands of patients have been studied.

More worrying still is the eagerness with which bio- synthetic erythropoietin (r-HuEPO) is being promoted as a potentially beneficial adjunct to autologous predonation. A small study from Japan [15] indicated that patients given r-HuEPO in a dose of 6,000 IU three times weekly become less anaemic than controls predonating the same number of units. However, the r-HuEPO patients also received in- travenous iron, while controls were given 2 tablets of fer- rous sulphate daily. This difference in supportive therapy makes assessment of the effect of r-HuEPO impossible. The authors’ conclusion that autologous predeposit with r-HuEPO ‘has the potential to lower morbidity, mortality, and health care costs’ seems premature, given the small number of patients studied and the lack of data on safety.

A more rigorously designed study [16] has shown that r-HuEPO in a dose of 600 IU/kg body weight twice weekly does allow patients to predonate more blood. In assessing the safety of this procedure, the authors were reassured by the similar incidence of adverse reactions to donation in the r-HuEPO group and the controls. Twenty-nine mild or moderate symptoms were reported by the 23 r-HuEPO

patients, and 32 by the 24 controls, suggesting a high reac- tion rate overall, but more significant was the occurrence of a myocardial infarct in a control patient and a peripheral arterial thrombosis in an erythropoietin-treated patient. The authors’ assumption that these events were unrelated to either the aggressive predeposit schedule or the treat- ment with erythropoietin may not be justified.

There is conflicting evidence on the relationship be- tween r-HuEPO and thrombotic events when used in pa- tients with end-stage renal disease [17, 181. In the only controlled study reported so far, 11 of 78 r-HuEPO-treated patients thrombosed their shunts, compared with 1 of 40 patients given placebo [18]. It is not yet clear whether the risk of thrombosis relates to the increase in haematocrit and blood viscosity in these patients, or whether there are more specific effects on the coagulation mechanism, but this po- tential danger is of particular concern when patients with ischaemic heart disease and other elderly patients in autol- ogous predeposit programmes are being subjected to in- tensive venesection.

Such invasive and potentially harmful methods of blood conservation should only be undertaken with extreme cau- tion, and data relating the risks of such treatment to the risks of homologous transfusion should be gathered system- atically. Large scale studies are required before a conclu- sion can be made that these new procedures add to patient safety.

References

Cohn LH, Fosberg AM, Anderson WP, Collins JJ: The effects of phlebotomy, hemodilution, and autologous transfusion on systemic oxygenation and whole blood utilization in open heart surgery. Chest 1975;68:283-287. Martin E, Hansen E, Peter K: Acute limited normovolaemic hemo- dilution: A method for avoiding homologous transfusion. World J Surg 1987;11:53-59. McCarthy PM, Popovsky MA, Schaff HV, et al: Effect of blood conservation efforts in cardiac operations at the Mayo Clinic. Mayo Clin Proc 1988;63:225-229. Breyer RH, Engelman RM, Rouson JA, Lemeshaw S: Blood con- servation for myocardial revascularisation. J Thorac Cardiovasc Surg 1987;93:512-522. Giordano GF, Goldman DS, Manimana RB, et al: Intraoperative autotransfusion in cardiac operations. J Thorac Cardiovasc Surg

Solomon MD, Rutledge ML, Kane LE, Yawn DH: Cost compari- son of intraoperative autologous versus homologous transfusion. Transfusion 1988;28:279-382. Guidelines for Autologous Blood Transfusion. Vox Sang 1989;

Guidelines for Autologous Transfusion. Clin Lab Haematol 1988;

1988;96:382-386.

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Bush M, Eble B, Heilbron D. Vyas G: Risk associated with trans- fusion of HIV-antibody-negative blood. N Engl J Med 1990; 332: 850-85 1. Hickman M, Mortimer JY, Rawlinson VI: Donor screening for HIV How many false negatives? Lancet 1988;i:1221. Mosley JW, Aach RD, Hollinger FB, et al: Non-A, Non-B hepatitis and antibody to hepatitis C virus. JAMA 1990;263:77-78. Tomasulo PA, Anderson AJ, Paluso MB, et al: A study of criteria for blood donor deferral. Transfusion 1980;20:511-518. Ogata H, Iinuma N, Nagashima K, Akabane T: Vasovagal reac- tions in blood donors. Transfusion 1980;20:679-683. McVay PA, Andrews A, Kaplan EB, et al: Donation reactions among autologous donors. Transfusion 1990;30:249-252. Maeda H, Hitomi Y, Hirata R, et al: Erythropoietin and autologous blood donation. Lancet 1989;ii:284. Goodnough LT, Rudnick S, Price TH, et al: Increased preoperative collection of autologous blood with recombinant human erythro- poietin therapy. N Engl J Med 1989;321:1163-1168.

17 Eschbach JW, Abdulhadi MH, Browne JK, et al: Recombinant human erythropoietin in anemic patients with end-stage renal dis- ease. Ann Intern Med 1989;iii:992-1OOO.

18 Canadian Erythropoietin Study Group. Association between hu- man recombinant erythropoietin and quality of life and exercise capacity of patients receiving haemodialysis. Br Med J 1990; 300~573-578.

Received: February 12,1991

J. Gillon, MD FRCP (Ed) Scottish National Blood Transfusion Service South-East Regional Centre Department of Transfusion Medicine Royal Infirmary Edinburgh EH3 9HB (UK)