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Pro: Preoperative autologous blood donation has a role in cardiac surgery

2003; Elsevier BV; Volume: 17; Issue: 1 Linguagem: Inglês

10.1053/jcan.2003.23

1532-8422

Keyvan Karkouti, Stuart McCluskey,

Blood donation and transfusion practices

Why has the use of preoperative autologous blood donation (PAD), which markedly increased in the 1980s and early 1990s, been declining recently?1Brecher ME Goodnough LT The rise and fall of preoperative autologous blood donation.Transfusion. 2001; 41: 1459-1462Crossref PubMed Scopus (76) Google Scholar The short answer is that PAD is no longer thought to be cost-effective principally because of the virtual elimination of hepatitis and human immunodeficiency viruses from the donor blood pool. This perception is supported by an economic evaluation published in the New England Journal of Medicine, which found that in cardiac surgery the cost of PAD per quality adjusted life year was approximately US$500,000.2Etchason J Petz L Keeler E et al.The cost-effectiveness of preoperative autologous blood donations.N Engl J Med. 1995; 332: 719-724Crossref PubMed Scopus (462) Google Scholar Based on this estimate, PAD is not cost-effective when compared with many other medical interventions.3Birkmeyer JD Goodnough LT AuBuchon JP et al.The cost-effectiveness of preoperative autologous blood donation for total hip and knee replacement.Transfusion. 1993; 33: 544-551Crossref PubMed Scopus (240) Google Scholar Other economic evaluations have found similarly high (or even higher) estimates for the cost-effectiveness of PAD in both cardiac and noncardiac surgery.3Birkmeyer JD Goodnough LT AuBuchon JP et al.The cost-effectiveness of preoperative autologous blood donation for total hip and knee replacement.Transfusion. 1993; 33: 544-551Crossref PubMed Scopus (240) Google Scholar, 4Birkmeyer JD AuBuchon JP Littenberg B et al.Cost-effectiveness of preoperative autologous donation in coronary artery bypass grafting.Ann Thorac Surg. 1994; 57: 161-169Abstract Full Text PDF PubMed Scopus (147) Google Scholar, 5Goodnough LT Grishaber JE Birkmeyer JD et al.Efficacy and cost-effectiveness of autologous blood predeposit in patients undergoing radical prostatectomy procedures.Urology. 1994; 44: 226-231Abstract Full Text PDF PubMed Scopus (92) Google Scholar Should clinicians, therefore, stop offering PAD to patients and spend the increasingly limited health care dollars on more worthwhile interventions? One way to answer this question is to assess the reliability and validity of the economic evaluations. In other words, are the results comparable, and were all the relevant costs and health effects (benefits and risks) of PAD appropriately assessed? To answer these questions, the authors review the health effects and costs of PAD and their influence on cost-effectiveness. Then, after providing a brief overview of economic evaluations in general, the authors assess how the economic evaluations comparing PAD with allogeneic blood transfusion incorporated these costs and health effects and how their conclusions compare with each other. Preoperative autologous blood donation reduces the need for allogeneic blood transfusion. A meta-analysis of studies in multiple surgical procedures found that patients who donated autologous blood were less likely (odds ratio, 0.17; 95% confidence interval, 0.08-0.32) to require allogeneic blood than those who did not.6Forgie MA Wells PS Laupacis A et al.Preoperative autologous donation decreases allogeneic transfusion but increases exposure to all red blood cell transfusion: results of a meta-analysis.Arch Intern Med. 1998; 158: 610-616Crossref PubMed Scopus (200) Google Scholar By providing whole blood for transfusion, autologous predonation for cardiac surgery may have the added benefit of reducing exposure to other allogeneic blood products such as fresh frozen plasma.7Britton LW Eastlund DT Dziuban SW et al.Predonated autologous blood use in elective cardiac surgery.Ann Thorac Surg. 1989; 47: 529-532Abstract Full Text PDF PubMed Scopus (80) Google Scholar Patients who predonate their own blood, therefore, are at a lower risk for the infectious and noninfectious hazards that are associated with allogeneic blood and blood products. On the other hand, the overall rate of blood transfusion (autologous plus allogeneic) is higher in patients who predonate their own blood (odds ratio, 3.03; 95% confidence interval, 1.7-5.4).6Forgie MA Wells PS Laupacis A et al.Preoperative autologous donation decreases allogeneic transfusion but increases exposure to all red blood cell transfusion: results of a meta-analysis.Arch Intern Med. 1998; 158: 610-616Crossref PubMed Scopus (200) Google Scholar This is partly because of incomplete erythropoiesis, which means that patients who are autologous donors do not completely replenish their red blood cell mass before surgery.8Kasper SM Gerlich W Buzello W Preoperative red cell production in patients undergoing weekly autologous blood donation.Transfusion. 1997; 37: 1058-1062Crossref PubMed Scopus (51) Google Scholar To a much greater extent, however, the higher transfusion rate is because of inappropriately liberal criteria that physicians use for transfusion of autologous blood, which should be amenable to the institution of quality control measures aimed at achieving adherence to appropriate transfusion guidelines.9Dupuis J-Y Bart B Bryson G Robblee J Transfusion practices among patients who did and did not predonate autologous blood before elective cardiac surgery.CMAJ. 1999; 160: 997-1002PubMed Google Scholar Overtransfusion of autologous blood is detrimental because autologous blood is not completely without risk—it has some of the same hazards of allogeneic blood transfusion. The net health benefit of autologous predonation depends, therefore, on the relative safety of autologous blood in comparison with allogeneic blood. Over the past 2 decades, because of improvements in donor and blood screening, the risk of transmission of hepatitis B, C, and the human immunodeficiency viruses (HIV) by allogeneic blood has become negligible (current estimates place this risk at approximately 1 in 100,000 transfusions for hepatitis and 1 in 750,000 for HIV).10Chamberland ME Emerging infectious agents: Do they pose a risk to the safety of transfused blood and blood products?.Clin Infect Dis. 2002; 34: 797-805Crossref PubMed Scopus (48) Google Scholar Consequently, the benefit that PAD confers to patients by reducing this risk has very little impact on its cost-effectiveness. In fact, it has been argued that because the risk of transfusion-related mortality from hepatitis and HIV is now lower than from acute hemolytic reactions, which occur when a unit of blood (either autologous or allogeneic) is mistakenly transfused to a patient who has a different ABO blood type (see below), autologous predonation actually increases the risk of transfusion-related mortality by increasing the overall transfusion rate.1Brecher ME Goodnough LT The rise and fall of preoperative autologous blood donation.Transfusion. 2001; 41: 1459-1462Crossref PubMed Scopus (76) Google Scholar This argument, however, is overly simplistic because it does not take into account any of the other benefits of PAD, some of which have a much greater influence on postoperative morbidity and mortality than acute hemolytic reactions. Several new infectious agents have been identified that may pose a danger to the allogeneic blood supply.10Chamberland ME Emerging infectious agents: Do they pose a risk to the safety of transfused blood and blood products?.Clin Infect Dis. 2002; 34: 797-805Crossref PubMed Scopus (48) Google Scholar These include non–A-E hepatitis viruses and the prion protein responsible for variant Creutzfeldt-Jakob disease (vCJD). Recent work has focused attention on a new family of viruses called SENV as a potential cause of post-transfusion non–A-E hepatitis. The SEN virus family is transmitted by transfusion, approximately 2% of donors test positive for it, and the proportion of cardiac surgery patients with evidence of new infection with SENV is 10 times higher among those who received blood transfusions (30%) than among those who did not (3%).10Chamberland ME Emerging infectious agents: Do they pose a risk to the safety of transfused blood and blood products?.Clin Infect Dis. 2002; 34: 797-805Crossref PubMed Scopus (48) Google Scholar However, it is not yet clear if SENV is one of the primary agents of non–A-E hepatitis.10Chamberland ME Emerging infectious agents: Do they pose a risk to the safety of transfused blood and blood products?.Clin Infect Dis. 2002; 34: 797-805Crossref PubMed Scopus (48) Google Scholar Although no cases of transmission of vCJD by blood transfusion have been reported, this issue has generated a great deal of concern. The concern is warranted because very little is known about the responsible prion protein other than that it has a very long incubation period, that it is present in WBC-rich organs such as spleen, and that presymptomatic vCJD patients may be able to transmit the disease through donated blood.10Chamberland ME Emerging infectious agents: Do they pose a risk to the safety of transfused blood and blood products?.Clin Infect Dis. 2002; 34: 797-805Crossref PubMed Scopus (48) Google Scholar, 11Coulthart MB Cashman NR Variant Creutzfeldt-Jakob disease: A summary of current scientific knowledge in relation to public health.Can Med Assoc J. 2001; 165: 51-58Google Scholar By autologous predonation, patients avoid the risks of infection with these and other infectious agents. This benefit, however, is still theoretical and is not quantifiable; thus, it cannot be included in the economic analyses. Transfusion-related acute lung injury (TRALI) is an immune-mediated transfusion reaction that is thought to be triggered by antibodies in the plasma of the blood donor.12Popovsky MA Transfusion-related acute lung injury.Curr Opin Hematol. 2000; 7: 402-407Crossref PubMed Scopus (41) Google Scholar In its classic presentation, it is indistinguishable from adult respiratory distress syndrome, but it frequently presents as milder forms of respiratory distress. Symptoms always arise within 1 to 6 hours of transfusion and are usually resolved within 48 to 96 hours, but it is fatal in up to 8% of cases. The estimated incidence of TRALI is 1 in 5,000 transfusions, and most experts agree that it is significantly underdiagnosed. It is the second most common cause of major morbidity and death attributable to transfusion.13Williamson LM Lowe S Love EM et al.Serious hazards of transfusion (SHOT) initiative: Analysis of the first two annual reports.BMJ. 1999; 319: 16-19Crossref PubMed Scopus (288) Google Scholar By virtue of its morbidity and mortality, TRALI is one of the most important complications of allogeneic blood transfusion today.12Popovsky MA Transfusion-related acute lung injury.Curr Opin Hematol. 2000; 7: 402-407Crossref PubMed Scopus (41) Google Scholar Another complication of allogeneic blood is immune suppression, which is commonly referred to as transfusion-related immune modulation (TRIM). The mechanism of TRIM has not been clarified; it may be caused by donor white blood cells, or donor plasma.14Vamvakas EC Pineda AA Autologous transfusion and other approaches to reduce allogeneic blood exposure.Best Pract Res Clin Haematol. 2000; 13: 533-547Abstract Full Text PDF Scopus (23) Google Scholar The clinical significance of TRIM is still being debated. The prevailing hypothesis is that the immune suppression may increase the risk of postoperative bacterial infection. A recent comprehensive review of the evidence concluded that TRIM probably results in a small (less than 10%) increase in the risk of postoperative infection.15Vamvakas EC Blajchman MA Deleterious clinical effects of transfusion-associated immunomodulation: Fact or fiction?.Blood. 2001; 97: 1180-1195Crossref PubMed Scopus (367) Google Scholar Furthermore, the authors state that “a risk as small as a 10% increase in the risk of postoperative infection—if it really exists—represents a clinically important complication of transfusion that ought to be prevented.”15Vamvakas EC Blajchman MA Deleterious clinical effects of transfusion-associated immunomodulation: Fact or fiction?.Blood. 2001; 97: 1180-1195Crossref PubMed Scopus (367) Google Scholar By avoiding the immune-modulated complications of allogeneic blood transfusion, patients who receive autologous blood should fare better than those who receive allogeneic blood. The majority of studies that have examined this hypothesis have found improved postoperative outcomes (reduced postoperative infections and duration of hospital stay) in patients receiving autologous blood,15Vamvakas EC Blajchman MA Deleterious clinical effects of transfusion-associated immunomodulation: Fact or fiction?.Blood. 2001; 97: 1180-1195Crossref PubMed Scopus (367) Google Scholar, 16Duffy G Neal KR Differences in postoperative infection rates between patients receiving autologous and allogeneic blood transfusion: A meta-analysis of published randomized and nonrandomized studies.Transfus Med. 1996; 6: 325-328Crossref PubMed Scopus (72) Google Scholar, 17Vanderlinde ES Heal JM Blumberg N Autologous transfusion.BMJ. 2002; 324: 772-775Crossref PubMed Scopus (88) Google Scholar but their results are not conclusive because of flaws in their design or analysis.14Vamvakas EC Pineda AA Autologous transfusion and other approaches to reduce allogeneic blood exposure.Best Pract Res Clin Haematol. 2000; 13: 533-547Abstract Full Text PDF Scopus (23) Google Scholar, 15Vamvakas EC Blajchman MA Deleterious clinical effects of transfusion-associated immunomodulation: Fact or fiction?.Blood. 2001; 97: 1180-1195Crossref PubMed Scopus (367) Google Scholar Nevertheless, they do provide the strongest argument for the continued use of autologous blood because even a small improvement in postoperative outcomes would have a large effect on the cost-effectiveness of PAD. Other serious, but extremely rare, adverse immune-mediated events associated with allogeneic blood transfusions include post-transfusion purpura, graft-versus-host disease, and acute hemolytic reactions that are occasionally caused by minor non-ABO red-cell antibodies that are not detected by the routine preoperative blood assay (these minor antibodies usually result in mild, delayed hemolytic reactions).13Williamson LM Lowe S Love EM et al.Serious hazards of transfusion (SHOT) initiative: Analysis of the first two annual reports.BMJ. 1999; 319: 16-19Crossref PubMed Scopus (288) Google Scholar, 18Goodnough LT Brecher ME Kanter MH AuBuchon JP Transfusion medicine: I. blood transfusion.N Engl J Med. 1999; 340: 438-447Crossref PubMed Scopus (808) Google Scholar Because these complications are extremely rare, however, their impact on the cost-effectiveness matrix is negligible. Another fact or that affects the cost-effectiveness of PAD is the anxiety that patients feel about receiving other people's blood, in particular about the risk of transmission of viral infections. To alleviate this anxiety, patients are willing to pay large sums of money to predonate their own blood, even after they are reassured about the safety of allogeneic blood.19Lee SJ Liljas B Churchill WH et al.Perceptions and preferences of autologous blood donors.Transfusion. 1998; 38: 757-763Crossref PubMed Scopus (40) Google Scholar This benefit of autologous predonation is quantifiable and should be included in the economic analyses (in a cost-utility format) to obtain an accurate measure of the cost-effectiveness of PAD. Autologous blood is not completely safe. One serious complication that can occur with both autologous and allogeneic blood transfusion is acute hemolytic reaction, which occurs when a unit of blood is mistakenly transfused to a patient who has a different ABO blood type. Although this is one of the most frequently reported causes of transfusion-related mortality and major morbidity,13Williamson LM Lowe S Love EM et al.Serious hazards of transfusion (SHOT) initiative: Analysis of the first two annual reports.BMJ. 1999; 319: 16-19Crossref PubMed Scopus (288) Google Scholar it is very rare—the estimated incidence is less than 1 in 500,000 transfusions.18Goodnough LT Brecher ME Kanter MH AuBuchon JP Transfusion medicine: I. blood transfusion.N Engl J Med. 1999; 340: 438-447Crossref PubMed Scopus (808) Google Scholar Another potential risk is bacterial contamination of the collected blood, which can result in sepsis if transfused. The rate of sepsis is also extremely low, less than 1 in 500,000 for allogeneic blood,18Goodnough LT Brecher ME Kanter MH AuBuchon JP Transfusion medicine: I. blood transfusion.N Engl J Med. 1999; 340: 438-447Crossref PubMed Scopus (808) Google Scholar and probably only slightly higher for autologous blood (because the units are generally stored longer, increasing the time available for the bacteria to proliferate). Thus, the contribution of these risks to the cost-effectiveness matrix is negligible. Finally, serious adverse events have been associated with the blood donation process, including hemodynamic instability and acute coronary events.20Popovsky MA Whitaker B Arnold NL Severe outcomes of allogeneic and autologous blood donation: frequency and characterization.Transfusion. 1995; 35: 734-737Crossref PubMed Scopus (173) Google Scholar, 21Kasper SM Ellering J Stachwitz P et al.All adverse events in autologous blood donors with cardiac disease are not necessarily caused by blood donation.Transfusion. 1998; 38: 669-673Crossref PubMed Scopus (23) Google Scholar Although uncommon, these events occur more frequently in autologous blood donors than allogeneic donors (approximately 1 in 17,000 and 1 in 200,000 donations, respectively),20Popovsky MA Whitaker B Arnold NL Severe outcomes of allogeneic and autologous blood donation: frequency and characterization.Transfusion. 1995; 35: 734-737Crossref PubMed Scopus (173) Google Scholar which is not surprising considering that many autologous blood donors suffer from underlying illnesses.22AuBuchon JP Popovsky MA The safety of preoperative autologous blood donation in the nonhospital setting.Transfusion. 1991; 31: 513-517Crossref PubMed Scopus (85) Google Scholar All adverse events that occur during the blood donation period, however, are not necessarily due to the donation process.21Kasper SM Ellering J Stachwitz P et al.All adverse events in autologous blood donors with cardiac disease are not necessarily caused by blood donation.Transfusion. 1998; 38: 669-673Crossref PubMed Scopus (23) Google Scholar Nevertheless, any serious morbidity that is caused by autologous donation would have a large negative impact on its cost-effectiveness.2Etchason J Petz L Keeler E et al.The cost-effectiveness of preoperative autologous blood donations.N Engl J Med. 1995; 332: 719-724Crossref PubMed Scopus (462) Google Scholar Obtaining accurate cost estimates is one of the most difficult (and important) parts of any economic analysis.23Petitti DB Meta-analysis, Decision Analysis, and Cost-Effectiveness Analysis: Methods for Quantitative Synthesis in Medicine. Oxford University Press, New York1994Google Scholar Not surprisingly, the published estimates for the production costs (the direct and overhead costs needed to produce a product or service)23Petitti DB Meta-analysis, Decision Analysis, and Cost-Effectiveness Analysis: Methods for Quantitative Synthesis in Medicine. Oxford University Press, New York1994Google Scholar of autologous and allogeneic blood vary widely. For example, a multicenter study of blood transfusion costs found that the costs range from $281 to $420 for autologous blood and from $158 to $309 for allogeneic blood at different hospitals.24Forbes JM Anderson MD Anderson GF et al.Blood transfusion costs: A multicenter study.Transfusion. 1991; 31: 318-323Crossref PubMed Scopus (136) Google Scholar Despite the difficulty in obtaining reliable cost estimates, it seems fair to conclude that autologous blood costs more to produce than allogeneic blood because all but one of the economic analyses found this to be the case (see below). The 2 biggest cost drivers for autologous blood are personnel and wastage costs.25Tretiak R Laupacis A Riviere M et al.Cost of allogeneic and autologous blood transfusion in Canada.Can Med Assoc J. 1996; 154: 1501-1508Google Scholar Personnel costs are higher for autologous blood collection because it does not benefit from the same economy of scale that allogeneic blood collection does; autologous blood accounts for less than 5% of the overall blood supply.1Brecher ME Goodnough LT The rise and fall of preoperative autologous blood donation.Transfusion. 2001; 41: 1459-1462Crossref PubMed Scopus (76) Google Scholar Wastage costs are higher for autologous blood because a large proportion (up to 80% depending on the type of surgery) of the blood is not needed by patients and is therefore discarded.26Renner SW Howanitz PJ Bachner P Preoperative autologous blood donation in 612 hospitals. A College of American Pathologists' Q-Probes study of quality issues in transfusion practice.Arch Pathol Lab Med. 1992; 116: 613-619PubMed Google Scholar In stark contrast, less than 10% of collected allogeneic blood is wasted, usually because of expired shelf-life.25Tretiak R Laupacis A Riviere M et al.Cost of allogeneic and autologous blood transfusion in Canada.Can Med Assoc J. 1996; 154: 1501-1508Google Scholar For PAD to approach acceptable cost-effectiveness thresholds, steps need to be taken to reduce these costs. Large hospital-based PAD programs can substantially reduce the personnel costs of autologous blood collection by, for example, simultaneously collecting blood from several patients. The discard rate of autologous blood can be markedly reduced by refining the patient selection criteria so that blood is collected only from those who have a high likelihood of requiring blood transfusions rather than from every patient undergoing a particular procedure, thereby increasing the utilization rate of autologous blood. Prediction rules exist that can help identify such patients in cardiac surgery.27Karkouti K Cohen MM McCluskey SA et al.A multivariable model for predicting the need for blood transfusion in patients undergoing first-time elective coronary bypass grafting.Transfusion. 2001; 41: 1193-1203Crossref PubMed Scopus (95) Google Scholar Economic evaluation is becoming established as one of the tools for decision-making at the policy level in situations in which more than 1 therapeutic option is available for management of the same condition.28Jefferson T Demicheli V Quality of economic evaluations in health care.BMJ. 2002; 324: 313-314Crossref PubMed Scopus (38) Google Scholar Decision analysis is a quantitative approach to economic evaluation that assesses the relative value of the different decision options by (1) breaking the clinical scenario down into its components (ie, therapeutic options, possible outcomes), (2) creating a decision tree to represent the components, (3) assigning probabilities for the uncertainties in the tree and values to the outcomes (which are obtained from the medical literature or expert opinion), and (4) using statistical methods to estimate the net value of each different decision option.23Petitti DB Meta-analysis, Decision Analysis, and Cost-Effectiveness Analysis: Methods for Quantitative Synthesis in Medicine. Oxford University Press, New York1994Google Scholar There are 3 types of decision analysis based on how the values of the outcomes are measured. In cost-benefit analysis, values are assessed in monetary terms only. In cost-effectiveness analysis, at least some of the consequences of the options are assessed in nonmonetary terms, such as years of life saved. In cost-utility analysis, patients' preferences, defined as levels of satisfaction, distress, or desirability that people associate with the health outcome, are also incorporated in the analysis.23Petitti DB Meta-analysis, Decision Analysis, and Cost-Effectiveness Analysis: Methods for Quantitative Synthesis in Medicine. Oxford University Press, New York1994Google Scholar An intervention is considered to be cost-effective if it is (1) less costly and at least as effective as the alternative; (2) more effective and more costly, with the added benefit worth the added cost; or (3) less effective and less costly, with the added benefit of the alternative not worth the added cost.23Petitti DB Meta-analysis, Decision Analysis, and Cost-Effectiveness Analysis: Methods for Quantitative Synthesis in Medicine. Oxford University Press, New York1994Google Scholar An intervention is considered to be dominant if it is both less costly and more effective than the alternative. Many aspects of economic analyses—such as the modelling of the clinical scenario, the cost estimates of the intervention, and the assignment of values to the outcomes—are at the discretion of the investigators and open to bias.29Kassirer JP Angell M The Journal's policy on cost-effectiveness analyses.N Engl J Med. 1994; 331: 669-670Crossref PubMed Scopus (214) Google Scholar It is therefore important to carefully assess the methodology and content of the cost-effectiveness evaluations of PAD before basing any policy decisions on their conclusions. Explicit criteria have been published to help assess the methodologic quality of economic evaluations, and a recent review found that those on PAD generally fared well in this respect.30Fergusson D van Walraven C Coyle D Laupacis A Economic evaluations of technologies to minimize perioperative transfusion: A systematic review of published studies.Transfus Med Rev. 1999; 13: 106-117Abstract Full Text PDF PubMed Scopus (29) Google Scholar However, methodologic soundness, although important, is not all that is required to ensure validity. Equally important is whether the evaluations accurately represented the costs and health effects of PAD and whether their results are reproducible—reproducibility, after all, is the cornerstone for validating any scientific model.23Petitti DB Meta-analysis, Decision Analysis, and Cost-Effectiveness Analysis: Methods for Quantitative Synthesis in Medicine. Oxford University Press, New York1994Google Scholar Table 1 includes a list of the published economic evaluations that compared PAD with allogeneic blood transfusion, the type of analyses that they used, the variables that were included in their decision models, and their results. A comparison of the results shows that not only are the evaluations not reproducible but that their conclusions are contradictory. One reason for this may be that the evaluations used different surgical populations, but even those using similar populations had different conclusions. Rather, their conclusions are not reproducible because they did not accurately represent the health effects and costs of PAD. Table 1 lists the health effects and table 2 lists the production cost estimates that were included in the evaluations.Table 2Production cost estimates for PAD that were used in the economic analysesProduction Cost Differential (Autologous Minus Allogeneic Blood) ($)StudyNot Including Wastage CostsIncluding Wastage CostsCommentsElawad et al31Elawad A Benoni G Montgomery F et al.Cost-effectiveness of blood substitution in elective orthopedic operations.Acta Orthop Scand. 1991; 62: 435-439Crossref PubMed Scopus (13) Google Scholar18Birkmeyer et al3Birkmeyer JD Goodnough LT AuBuchon JP et al.The cost-effectiveness of preoperative autologous blood donation for total hip and knee replacement.Transfusion. 1993; 33: 544-551Crossref PubMed Scopus (240) Google Scholar24Birkmeyer et al4Birkmeyer JD AuBuchon JP Littenberg B et al.Cost-effectiveness of preoperative autologous donation in coronary artery bypass grafting.Ann Thorac Surg. 1994; 57: 161-169Abstract Full Text PDF PubMed Scopus (147) Google Scholar2181Goodnough et al5Goodnough LT Grishaber JE Birkmeyer JD et al.Efficacy and cost-effectiveness of autologous blood predeposit in patients undergoing radical prostatectomy procedures.Urology. 1994; 44: 226-231Abstract Full Text PDF PubMed Scopus (92) Google Scholar983-303Range is for 2 to 4 unit donationsHealy et al32Healy JC Frankforter SA Graves BK et al.Preoperative autologous blood donation in total-hip arthroplasty: A cost-effectiveness analysis.Arch Pathol Lab Med. 1994; 118: 465-470PubMed Google Scholar30Etchason et al2Etchason J Petz L Keeler E et al.The cost-effectiveness of preoperative autologous blood donations.N Engl J Med. 1995; 332: 719-724Crossref PubMed Scopus (462) Google Scholar4873-4,790Range is for different procedures (+$112 for CABG)Blumberg et al33Blumberg N Kirkey SA Heal JM A cost analysis of autologous and allogeneic transfusions in hip-replacement surgery.Am J Surg. 1996; 171: 324-330Abstract Full Text PDF PubMed Scopus (89) Google Scholar25-5081-263Range is for 2 to 5 unit donationsRoberts et al34Roberts WA Kirkley SA Newby M A cost comparison of allogeneic and preoperatively or intraoperatively donated autologous blood.Anesth Analg. 1996; 83: 129-133PubMed Google Scholar−33−2Tretiak et al25Tretiak R Laupacis A Riviere M et al.Cost of allogeneic and autologous blood transfusion in Canada.Can Med Assoc J. 1996; 154: 1501-1508Google Scholar72125Sonnenberg et al35Sonnenberg FA Gregory P Yomtovian R et al.The cost-effectiveness of autologous transfusion revisited: Implications of an increased risk of bacterial infection with allogeneic transfusion.Transfusion. 1999; 39: 808-817Crossref PubMed Scopus (75) Google Scholar63342 Open table in a new tab None of the evaluations included all of the important health effects of PAD in their decision trees, and the production cost estimates used were highly variable. Given these shortcomings, the evaluations are not able to resolve the debate about the cost-effectiveness of PAD. They do, however, provide the information required to determine the relative importance of the costs and health effects of PAD to the cost-effectiveness matrix, which allows the conditions in which PAD would be cost-effective to be identified.Table 1Economic analyses of PAD in comparison to allogeneic blood transfusionHealth Effects That Were Included in the Decision TreeStudyDesignViral InfectionsTRIMTRALIHemolytic Rctn.Other Immune*Pt PreferenceDonation RiskCost-EffectivenessElawad et al31Elawad A Benoni G Montgomery F et al.Cost-effectiveness of blood substitution in elective orthopedic operations.Acta Orthop Scand. 1991; 62: 435-439Crossref PubMed Scopus (13) Google ScholarC-BYNNNNNNPAD cost saving in orthopedic surgeryBirkmeyer et al3Birkmeyer JD Goodnough LT AuBuchon JP et al.The cost-effectiveness of preoperative autologous blood donation for total hip and knee replacement.Transfusion. 1993; 33: 544-551Crossref PubMed Scopus (240) Google ScholarC-EYNNYNNN$40,000-$1,467,000/QALY in orthopedic surgery; lowest estimate is for revision or bilateral joint replacementBirkmeyer et al4Birkmeyer JD AuBuchon JP Littenberg B et al.Cost-effectiveness of preoperative autologous donation in coronary artery bypass grafting.Ann Thorac Surg. 1994; 57: 161-169Abstract Full Text PDF PubMed Scopus (147) Google ScholarC-EYNNYNNN$508,000-$909,000/QALY in cardiac surgery; 2-5 unit donationsGoodnough et al5Goodnough LT Grishaber JE Birkmeyer JD et al.Efficacy and cost-effectiveness of autologous blood predeposit in patients undergoing radical prostatectomy procedures.Urology. 1994; 44: 226-231Abstract Full Text PDF PubMed Scopus (92) Google ScholarC-EYNNYNNN$531,000-$1,890,000/QALY in radical prostatectomy; 2-4 unit donationsHealy et al32Healy JC Frankforter SA Graves BK et al.Preoperative autologous blood donation in total-hip arthroplasty: A cost-effectiveness analysis.Arch Pathol Lab Med. 1994; 118: 465-470PubMed Google ScholarC-EYYNYNNNPAD dominant in orthopedic surgeryEtchason et al2Etchason J Petz L Keeler E et al.The cost-effectiveness of preoperative autologous blood donations.N Engl J Med. 1995; 332: 719-724Crossref PubMed Scopus (462) Google ScholarC-EYNNNNNN$235,000/QALY in orthopedic surgery; $494,000/QALY in cardiac surgeryBlumberg et al33Blumberg N Kirkey SA Heal JM A cost analysis of autologous and allogeneic transfusions in hip-replacement surgery.Am J Surg. 1996; 171: 324-330Abstract Full Text PDF PubMed Scopus (89) Google ScholarC-BNYNNNNNPAD cost saving in orthopedic surgeryRoberts et al34Roberts WA Kirkley SA Newby M A cost comparison of allogeneic and preoperatively or intraoperatively donated autologous blood.Anesth Analg. 1996; 83: 129-133PubMed Google ScholarC-BYNNYNNNPAD cost savingSonnenberg et al35Sonnenberg FA Gregory P Yomtovian R et al.The cost-effectiveness of autologous transfusion revisited: Implications of an increased risk of bacterial infection with allogeneic transfusion.Transfusion. 1999; 39: 808-817Crossref PubMed Scopus (75) Google ScholarC-UYYNYNNN$1470/QALY in cardiac surgery*Other immune-mediated adverse events associated with blood transfusion including post-transfusion purpura and graft-versus-host disease.Abbreviations: Pt, patient; Rctn, reaction; C-B, cost-benefit analysis; C-E, cost-effectiveness analysis; C-U, cost-utility analysis; TRIM, transfusion-related immune modulation; TRALI, transfusion-related acute lung injury; QALY, quality-adjusted life year; Y, yes; N, no. Open table in a new tab Abbreviations: Pt, patient; Rctn, reaction; C-B, cost-benefit analysis; C-E, cost-effectiveness analysis; C-U, cost-utility analysis; TRIM, transfusion-related immune modulation; TRALI, transfusion-related acute lung injury; QALY, quality-adjusted life year; Y, yes; N, no. The evaluations that assessed only the risk of viral infections and acute hemolytic reactions and used higher cost estimates for autologous than allogeneic blood found that PAD is not cost-effective (unless they used excessively high-risk estimates for viral infections). On the other hand, those that also accounted for the improvements in patient outcome because of PAD or used lower cost estimates for autologous than allogeneic blood found that PAD is cost-effective. The cost-effectiveness matrix of PAD is different now from what it was 10 to 20 years ago. Twenty years ago, the risk of transmission of viral infections by allogeneic blood was so high that reducing this risk was enough to make PAD cost-effective. Now, this risk is so low that achieving further reductions has a negligible effect on the cost-effectiveness of any blood conservation strategy, including PAD. The cost-effectiveness of PAD now primarily depends on 2 other factors: effect on postoperative outcomes and production costs.