Since blood transfusion is linked to the magnitude of the surgical procedure, comparing transfused patients to untransfused patients will always be confounded by infection risks due to factors related to the procedure. To control for these factors one must compare patients transfused with red cells from different sources or prepared in a manner which minimize infection risk. Patients transfused with homologous blood have infection rates several fold higher than recipients of equal values of autologous blood undergoing the same operative procedure (20-23). Homologous blood recipients have significantly longer hospital stays attributed to treating infections. The cost of a blood transfusion exceeds the cost of collection, storage and administration because of transfusion's association with length of stay. In this era of cost-containment the association with prolonged stay may ultimately curtail the use of blood. Homologous blood can be filtered to remove donor leukocytes which may be contributing to immune suppression and infection risk. A prospective randomized trial comparing the infection rates among colorectal cancer patients receiving filtered and unfiltered blood has been conducted (9). There were 17 infectious complications among the 56 recipients of whole blood and one infectious complication among the 48 recipients of filtered blood. Infections were prevented by the seemingly simplistic addition of a $25/filter to every bag of blood transfused. These clinical studies are very convincing: homologous blood transfusion is associated with increased risk of infection in every clinical situation examined. In multivariate analyses transfusion was a significant predictor of infection after consideration of other variables measured and in the majority of those studies transfusion was the single most significant factor. Patients receiving homologous blood exhibited an incidence of infectious complications that was approximately four times higher than patients receiving autologous blood. The association of transfusion with infection is found among patients undergoing surgery for cardiac, orthopedic and gastrointestinal disorders and for trauma as well as among unoperated patients transfused for bums and gastrointestinal bleeding. The observation that nosocomial infections are increased in these studies argues strongly that the association of transfusion with infection is not simply a reflection of transfusion as a marker of tissue destruction and contamination. Infections that develop in transfused patients away from the site of trauma or in the absence of trauma, cannot be attributed to the quantity of tissue destroyed or to the degree of bacterial contamination. Filtered blood can remove leukocytes and prevent postoperative infections. Since filtering blood can significantly reduce the incidence of infection among transfused patients, all transfused blood will be passing through filters in the very near future. EXPERIMENTAL STUDIES RELATING BLOOD TRANSFUSION TO INCREASED RISK OF INFECTION Patients are extremely heterogeneous and even in prospective randomized trials, factors which influence patients' participation affect the outcome despite double-blinding and randomization. In animal studies using syngeneic strains with identical housing, lighting, access to food and water, control over the extent of injury, use of antibiotics and exposure to other variables the influence of a single variable such as blood transfusion can be measured. Dr. Waymack's laboratory has intensively studied parameters which interact with transfusion in

Abstract While blood transfusions can be life saving, the associated risk of transfusing allogeneic blood is significant. The most common patient fears are transfusion-transmitted diseases such as HIV, Hepatitis B and C and West Nile Virus; however, the known risk of transmitting these diseases is quite small. More common complications are due to immunosuppression which can cause an increased risk of cancer recurrence in the oncologic patient and a significantly increased risk of infection. In trauma patients, it has been shown that the risk of infection increases with each additional unit of blood transfused. Currently, about 2.2 units of platelets and 3.3 units of red blood cells are administered following high-dose chemotherapy and an APBSCT. At the Center for Bloodless Medicine and Surgery at Pennsylvania Hospital, many procedures are now being completed without the use of blood products. We have previously reported the ability to perform bloodless APBSCT (Ballen, et al. J Clin Oncol2004;22:4087-4094). Knowing that blood transfusions can increase the risk of infection, we wanted to evaluate this transfusion-free population to determine if there was a correlation between infection rates and blood transfusions in the high risk transplant population. We performed a retrospective chart review of 46 patients with multiple myeloma (22), lymphoma (22) and breast cancer (2) who underwent a bloodless APBSCT in our center. Prior to transplantation, all patients recieved standard transplant doses of cyclophosphamide, carmustine and etoposide (BCV) or Melphalan. A PubMed search was performed and the closest data set in terms of patient demographics was a study by Pereira, et al. who report the rate of infectious complications in 75 patients with myeloma (30), lymphoma (30) and breast cancer (15) who were transfused liberally following high-dose chemotherapy and APBSCT (Pereira, et al. Eur J Haematol2006;76:102-108). In our bloodless patients, 37% of the patients had at least one infection, compared to Pereira and colleagues’ rate of 68% (see table). Our results are also reported in the average number of infections per patient. This comparison demonstrates a substantial reduction in the rate of infection in the bloodless population. While immunosuppression and the resulting increased infection rates have been correlated to blood transfusions in other patients populations, to the best of our knowledge this is the first report that suggests decreased infection rates in transfusion-free transplant patients. This data provides further evidence to support the practice of blood management strategies in order to reduce or eliminate blood transfusions. Patients with at least one infection All infections per person Bacterial per person Viral per person Fungal per person Unknown per person Autologous Transplants (Pereira, et al.) 68% .64 .53 .01 .07 .03 Bloodless Autologous Transplants 37% .41 .39 0 0 .02

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risks of homologous blood transfusion, such a study is unethical. Less controversial would be randomization of patients likely to be transfused into an autologous blood program. A study utilizing multiple institutions in the Netherlands with over 500 colorectal cancer patients (23) found the relative risk of cancer recurrence for patients transfused with 1 -2 units of autologous blood was 1.78 compared to untransfused patients and 2.11 for recipients of 1 - 2 units of homologous blood. Both autologous and homologous transfusions were bufify coat poor, standard for the Netherlands. Blood transfusion, whether autologous or homologous, was associated with significantly increased risk of cancer recurrence but the risk for both groups was comparable. A randomized prospective study of colorectal cancer patients by Weiss et al., (34) from Munich randomized 120 patients to receive either homologous or autologous blood if transfusion were needed. With median follow-up of 21 months (9 - 48), the recurrence rate among homologous recipients is 29% compared to 17% among autologous recipients and was significant in both B (p = 0.032) and C (p = 0.006) tumors. Multivariate regression identified homologous blood as an independent prognostic factor (p = 0.008). EXPERIMENTAL STUDIES OF TRANSFUSION AND TUMOR GROWTH Experimental studies control for tumor burden (disease stage) and extent of the procedure including blood loss. Allogeneic blood transfusion produces profound changes in the immune systems of experimental animals which are analogous to those observed in man. Experimental studies have observed promotion or inhibition of tumor growth following allogeneic blood transfusions because the effect of transfusion on tumor growth is route-, tumor-, species-, and strain-specific. In mice, tail vein inoculation of basal call carcinoma produces pulmonary nodules which are inhibited by prior allogeneic transfusion while no effect is seen if the tumor is given subcutaneously (35). In the same strain, growth of subcutaneous adenocarcinoma is inhibited by transfusion while pulmonary nodules are unaffected. Timing of transfusion relative to tumor inoculation also determines subsequent tumor growth. Studies of tumor growth in experimental animals lack analogy to the situation in the cancer patient. The tumor has been present for years in patients with malignancies and some immunologic interaction between the host and the tumor has preceded the effects of surgery and blood transfusion. In experimental studies, tumor inoculation generally followed allogeneic transfusion. MISCELLANEOUS PHENOMENA ASSOCIATED WITH BLOOD TRANSFUSION Recurrent Abortion One of the most exciting, intriguing and controversial areas in which transfusion affects the outcome and has a therapeutic role is in the treatment of recurrent abortion. During pregnancy, lymphocyte function, as measured by responses to antigens, mitogens and homologous lymphocytes (MLR), is suppressed. Inhibition of lymphocyte function is due to serum factors, blocking antibodies which develop in response to trophoblast antigens. When spouses share HLA antigens, trophoblast antigens are not recognized by the pregnant woman's immune system, blocking antibodies are not produced, and the fetus is rejected. In 1981 Taylor and Faulk (36) induced suppressive sera in women suffering from recurrent spontaneous abortion and sharing HLA antigens with their spouse by transfusing the women with leukocyte-enriched plasma from

Transfusion Immunology and Medicine ◽

10.1201/9781482273441-27 ◽

1995 ◽

pp. 298-298

Keyword(s):

Blood Transfusion ◽

Tumor Growth ◽

Autologous Blood ◽

Experimental Studies ◽

Hla Antigens ◽

Cancer Recurrence ◽

Pulmonary Nodules ◽

Lymphocyte Function ◽

Homologous Blood ◽

Colorectal Cancer Patients

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Acute Isovolaemic Haemodilution: The Best Option for Autologous Blood Transfusion in Africa?

Tropical Doctor ◽

10.1177/004947559502500403 ◽

1995 ◽

Vol 25 (4) ◽

pp. 152-155 ◽

Cited By ~ 1

Author(s):

Zacharia A Berege ◽

Bart Jacobs ◽

Michael R Matasha ◽

Frank Mpelumbe ◽

Ernestini Kimaro

Keyword(s):

Blood Transfusion ◽

Blood Loss ◽

Autologous Blood ◽

Autologous Blood Transfusion ◽

Total Blood Volume ◽

East African ◽

Homologous Blood ◽

Total Blood ◽

Induction Of Anaesthesia ◽

Donated Blood

The purpose of this study was to identify the best method of autologous blood transfusion to be applied in an East African hospital. One hundred and nine consecutive patients for whom major blood loss was anticipated were enrolled. Seventeen patients donated 1 unit of blood 3 days preoperatively and 92 underwent acute isovolaemic haemodilution prior to induction of anaesthesia. For the haemodiluted patients a 2:1 ratio of sterile pryogen-free saline to collected blood was used. One of the 16 patients from whom 2 units were withdrawn by haemodilution experienced hypovolaemia which was rapidly restored by additional transfusion of colloid. Of the patients who donated blood preoperatively only 23.5% were autotransfused compared to 98.9% of the haemodiluted patients. Of the latter 23.9% (22) had an intraoperative blood loss exceeding 15% of their total blood volume and 7.6% (7) lost more than 25%. Only one received homologous blood in addition. For hospitals with limited blood bank facilities and regular cancellation of surgery, the use of acute isovolaemic haemodilution is recommended. A 3:1 ratio of saline to blood is now advised when 1 unit is withdrawn and a part replacement with crystalloid when 2 units are collected.

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These studies indicate that homologous blood transfusion affects the outcome of clinical diseases in both beneficial and adverse ways. Experimental situations are not suitable for randomized clinical trials - transfusions cannot be given to prevent the onset of diabetes or wound strength measured in man following receipt of homologous or autologous blood. These experimental observations indicate that the outcomes of numerous clinical diseases which have not been studied may be manipulated by the use of homologous blood or that transfusion should be avoided. Several studies indicate that changes in immune function following transfusion are permanent. The number of clinical phenomena associated with immune suppression and attributable to blood transfusion is unknown. SUMMARY Given the evidence presented here it would be foolish to suggest that transfusion of homologous blood has no immunologic consequences for the recipient. Blood transfusion is the oldest form of transplant - no one would argue that transplantation between unrelated individuals has no influience on the immune system. In organ transplantation the immunologic sequelae are permanent and there is evidence that the same is true following homologous blood transfusion. Lymphocytopenia is present one year following surgery for Crohn's disease if patients receive perioperative blood transfusion (43). Colorectal cancer patients transfused more than seven years prior to diagnosis have significantly reduced numbers of lymphocytes and lower natural killer cytotoxicity than colorectal cancer patients who have never been transfused (44). Transfusion of neonates causes suppression of lymphocyte reactivity which is still demonstrable 25 to 30 years later (45). There is evidence that transfusion at any time prior to elective surgery increases susceptibility to infectious complications (14) and otherwise healthy transfused individuals may be at increased risk of developing malignancies (46). All the longterm consequences of blood transfusion are not negative: Survival of transplants is prolonged by pretransplant transfusion and some women suffering from recurrent spontaneous abortion can deliver at term if previously transfused with their spouse's leukocytes. In the future we will be able to transfuse blood without causing immune perterbations and the consequent clinical phenomena. Studies presented here suggest that removal of donor leukocytes reduces the risk of infection and cancer recurrence. The technology has not reached the point of reducing the leukocyte number in transfused blood below 10^/unit. An alternative which is increasingly being utilized is autologous blood programs. Physicians are discovering that patients tolerate hemoglobin levels which were previously unacceptably low and many patients prefer being anemic over the risks of receiving homologous blood. Since transfusion is an identifier of high cost hospitalized patients, alternatives to routine blood use are being studied in hopes of safely reducing the costs of transfusion. REFERENCES 1. Jubert AV, Lee ET, Hersh EM, McBride CM. J Surg Res 15:399-403, 1973. 2. M 19 u4n ( s3t ) e3r4A6-M 35 , 2 W , i1n9c8h1u . rch RA, Keane RM, Shatney CH, Ernst CB, Nuidema GD. Ann Surg

Transfusion Immunology and Medicine ◽

10.1201/9781482273441-29 ◽

1995 ◽

pp. 300-300

Keyword(s):

Colorectal Cancer ◽

Blood Transfusion ◽

Cancer Patients ◽

Randomized Clinical Trials ◽

Elective Surgery ◽

Autologous Blood ◽

Homologous Blood ◽

Homologous Blood Transfusion ◽

One Year ◽

Colorectal Cancer Patients

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Assessment of Catheter-Associated Infection Risk with the Hickman Right Atrial Catheter

Infection Control ◽

10.1017/s0195941700060161 ◽

1984 ◽

Vol 5 (5) ◽

pp. 226-230 ◽

Cited By ~ 32

Author(s):

Peter C. Fuchs ◽

Marie E. Gustafson ◽

James T. King ◽

Patrick T. Goodall

Keyword(s):

Parenteral Nutrition ◽

Antibiotic Therapy ◽

Cancer Chemotherapy ◽

Infection Risk ◽

Right Atrial ◽

Risk Of Infection ◽

Primary Indication ◽

Increased Risk ◽

Atrial Catheter ◽

The Mean

AbstractOne hundred fifty Hickman right atrial catheters were inserted into 143 patients and were followed prospectively until removal. Primary indications for their use were: cancer chemotherapy (45), parenteral nutrition (35), antibiotic therapy (63), and miscellaneous (7). The overall catheter-associated infection rate was 12.0%. Since the mean duration of catheterization was 125 days, the infection/duration rate was 1.0/1,000 days of use. The risk of infection differed significantly according to the primary indication for catheterization: parenteral nutrition > antibiotic therapy > cancer chemotherapy. The increased risk of catheter-associated infection attributable to duration of catheterization was additive, and the per day risk of such infections remained constant regardless of duration. Nearly two-thirds of patients were discharged home with catheters in place, without adversely affecting infection risk.

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The effect of autologous blood salvage techniques upon bank blood usage and the cost of routine coronary revascularization

Perfusion ◽

10.1177/026765918600100402 ◽

1986 ◽

Vol 1 (4) ◽

pp. 239-244 ◽

Cited By ~ 9

Author(s):

Loren F Hiratzka ◽

James V Richardson ◽

Berkeley Brandt ◽

Donald B Doty ◽

Nicholas P Rossi ◽

...

Keyword(s):

Coronary Revascularization ◽

Autologous Blood ◽

Blood Bank ◽

Cell Saver ◽

Homologous Blood ◽

Homologous Blood Transfusion ◽

Blood Usage ◽

Potential Risks ◽

The Mean ◽

The Cost

Preservation of autologous blood during cardiac surgery may reduce the need for homologous blood transfusions. We reviewed our experience for patients undergoing primary coronary revascularization to determine the effect of the use of the Haemonetics Cell-Saver upon blood bank resources and upon the cost of operation. The quantity of homologous blood required by two groups of patients was compared. One group of 46 patients had operation prior to use of the Cell- Saver ; the other group of 31 patients was entered into Cell-Saver protocols. The mean number of homologous blood units transfused per patient fell strikingly (p < 0.0001) from 4.2 before to 0.5 after introduction of the Cell- Saver. Of the 31 patients in the Cell-Saver protocol, 71 % required no homologous blood while they received 2.5 units of autologous blood processed by the Cell-Saver. Related to this, the mean number of units prepared by typing and compatibility testing in anticipation of surgery fell from 10 units to five. The projected cost to the patient fell 23%. There were no adverse effects from the use of the Cell-Saver. We conclude that the use of the Cell-Saver is justified not only to reduce the potential risks of homologous blood transfusion, but also to reduce the strain upon blood bank resources and the patient cost of primary coronary revascularization.

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The Immunosuppressive Aspects of Blood Transfusion

Journal of Intensive Care Medicine ◽

10.1177/088506669200700405 ◽

1992 ◽

Vol 7 (4) ◽

pp. 176-188 ◽

Cited By ~ 29

Author(s):

Thomas A. Mickler ◽

David E. Longnecker

Keyword(s):

Blood Transfusion ◽

Red Blood Cells ◽

Blood Cells ◽

Renal Allograft ◽

Autologous Blood ◽

Immunosuppressive Effect ◽

Solid Cancer ◽

Infection Rates ◽

Allograft Survival ◽

Packed Red Blood Cells

Blood transfusion is associated with immunosuppression, although the exact etiology of the immunosuppressive effect is not fully understood. The clinical significance of the immunosuppressive effect of blood transfusion has been examined in three situations: (1) studies of renal allograft survival after renal transplantation, (2) outcome studies in patients who have had surgical resection of solid cancer tumors, and (3) studies of infection rates in postoperative patients. In each scenario, the data support the conclusion that transfusion is associated with immunosuppression as manifested by increased renal allograft survival, increased recurrence and mortality rates in patients with cancer, and increased infection rates in postoperative patients who are transfused. Not all studies demonstrate an immunosuppressive effect of transfusion. There are several possible explanations for these discrepancies. First, prognostic variables other than transfusion itself account for the outcome results in these retrospective studies. Second, the extent of immunosuppression may be influenced by the type of blood product transfused, the amount transfused, and the timing of the transfusion; these factors have not been considered in all studies. For example, whole blood has been implicated as having a greater immunosuppressive effect than packed red blood cells, and many studies have shown that more than three units of packed red blood cells are necessary to affect outcome. Controlled animal studies have tested the hypothesis that transfusions increase solid tumor growth or the risk for infection. These studies have yielded conflicting results. Nevertheless, evidence that blood transfusion influences clinical outcome mitigates that a decision to transfuse must consider both risks and benefits of a transfusion; the possible consequences of immunosuppression must be included among the risks. Use of autologous blood, erythropoietin, and, in the future, synthetic hemoglobin may lead to improved outcome in patients with certain disease processes.

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