Effect Of Allogeneic Blood Transfusion Research Articles

Predonation of autologous blood reduces perioperative allogenic transfusion requirement in grown-up patients with congenital heart disease☆

Adults with congenital heart diseases have a substantial risk for bleeding upon re-operations. Due to the detrimental effects of allogeneic blood transfusion, reduction of transfusion requirement is a major concern. To investigate the efficacy of autologous blood predonation (ABP), we focussed on a homogeneous subgroup of patients, with right ventricular outflow tract reconstruction. Prospectively collected data included 76 patients older than 16 years with repeated right ventricular outflow tract reconstruction from May 1995 to November 2006. In 27 patients, ABP was performed without any complication. Primary diagnoses included Tetralogy of Fallot in 50 patients and others in 26 patients. All patients had at least one previous operation, 62% had more than one. All patients received a homograft conduit between the right ventricle and the pulmonary artery. Preoperative haemoglobin was 123+/-15 g l(-1) in patients with ABP and 134+/-22 g l(-1) in the remainder (p=0.037), but was not significantly different after cardiopulmonary bypass until discharge from the intensive care unit. Significantly more patients without ABP required transfusion of allogeneic packed red cells (PRCs) (26 of 49 patients (53%) vs 4 of 27 patients (15%), p=0.001) and allogeneic fresh frozen plasma (FFP) (30 of 49 patients (61%) vs 6 of 27 patients (22%), p=0.002) than patients with ABP. Of 27 patients, 23 (85%) and 25 (93%) with ABP received their predonated PRC and FFP, respectively. Logistic regression analysis identified no ABP (p=0.005, odds ratio (OR) 5.4, 95% confidence interval (CI) 1.7-17.7) and time on extracorporeal circulation >83 min (p=0.009, OR 5.0, 95% CI 1.5-16.8) to be predictive for allogeneic blood transfusion. ABP can be safely performed in grown-up patients with congenital heart disease without complications. Patients without predonation of autologous blood exhibit a fivefold increased risk for requiring allogeneic blood transfusion.

Allogeneic Blood Transfusion Given Before Radiotherapy Is Associated with the Poor Clinical Outcome in Patients with Cervical Cancer

PurposeTo analyze the effect of allogeneic blood transfusion on clinical outcome in 119 patients with stage IIB cervical cancer who were treated with radiotherapy ± chemotherapy.Patients and MethodsMedical records were examined for hemoglobin levels before and during radiotherapy, history of allogeneic blood transfusions and the time point when transfusions were given. These factors were retrospectively analyzed along with other clinical risk factors for influences on the patients' clinical outcomes.ResultsThirty-two patients (26.9%) received packed red blood cell transfusion (mean, 3.4 units; range, 1 - 12 units) before or during radiotherapy. Median follow-up period was 39.3 months (range, 7.6 - 58.4 months). Patients with history of transfusion showed poorer metastasis-free survival and a trend toward poorer overall survival than non-transfused patients. When patients who received transfusions were sub-divided by the time of transfusion, those who received transfusions before radiotherapy had significantly poorer clinical outcome than those who received transfusions during radiotherapy. In a multivariable analysis, patients with pretreatment transfusion showed a higher risk of distant metastasis (HR = 3.75, 95% CI: 1.28 - 12.15, p = 0.017) and decreased overall survival rates (HR = 4.62, 95% CI: 1.15-18.54, p = 0.031) compared with those of other patients.ConclusionOur results suggest that allogeneic blood transfusions given before radiotherapy may be associated with higher incidence of distant metastases and decreased survival in patients with stage IIB cervical cancer.

Effect of Perioperative Allogeneic Red Blood Cell Transfusion on the Immune‐Inflammatory Response After Colorectal Cancer Resection

Cytokines play an important role in the acute-phase response to trauma. Few studies have analyzed the effects of allogeneic blood transfusion containing packed red blood cells (RBCs) on the early postoperative immune/inflammatory response after colorectal resection for cancer This study investigated whether allogeneic RBC transfusion influences the postoperative immune/inflammatory response of patients submitted to large bowel resection due to cancer. A total of 26 patients -- 15 men and 11 women, with a median age of 56.5 years (range 24-87 years) -- were prospectively studied. Blood samples were obtained preoperatively and on the first and fourth postoperative days for C-reactive protein (CRP), interleukin-6 (IL-6), and IL-10 assays and for CD4 and CD8 lymphocyte counts. Transfused (> or =3 and <3 units), and nontransfused patients were compared. Both IL-6 and IL-10 increased postoperatively in transfused patients (p < 0.01). The serum IL-6 level was higher in patients receiving > or =3 units of RBCs (p < 0.01). CRP increased postoperatively unrelated to blood transfusion. The CD8 count decreased (p < 0.04) in transfused subjects, whereas CD4 decreased (p < 0.01) only in major-transfusion patients. Perioperative allogeneic RBC transfusion enhances the inflammatory systemic response and decreased immunity in patients submitted to colorectal resection for cancer.

Deleterious Clinical Effects of Allogeneic Blood Transfusion–Related Immunomodulation

The debate about the existence of deleterious clinical effects of allogeneic blood transfusion (ABT)-related immunomodulation (TRIM) continues and is now concentrated on differing interpretations of findings of randomized controlled trials (RCTs). This review focuses on the results of studies reported during the last 5 years, especially recent RCTs, studies of the association of ABT with all-cause mortality, studies of the hypothesis attributing TRIM effects to WBC-derived soluble mediators that accumulate during storage, and studies comparing the risk of adverse outcomes before and after the implementation of WBC reduction of cellular blood components. When this literature is considered along with that available before 2001, the results from studies of adverse clinical TRIM effects remain contradictory. Based on the totality of the evidence, there seems to be an association between WBC-containing ABT and short-term (≤3 months posttransfusion) mortality that becomes manifest in cardiac surgery and in comparison with administration of allogeneic blood components filtered before storage. However, with the possible exception of cardiac surgery, there is no area in the extensive TRIM literature in which there is agreement among the studies or in which the observed clinical effects follow consistently from a postulated biologic mechanism. Allogeneic blood transfusion (ABT) results in the infusion into the recipient of large amounts of foreign antigens in soluble and cell-associated forms. The persistence of these antigens in the circulation of the recipient may create conditions that allow for the development of immune down-regulation. Evidence from a variety of sources indicates that ABT enhances the survival of renal allografts 1 and may increase the recurrence rate of resected malignant neoplasms 2 and the incidence of postoperative bacterial infections, 3-8 as well as reduce the recurrence rate of Crohn disease 9 and/or activate infections with cytomegalovirus or HIV. 10 This syndrome, the mechanisms and clinical relevance of which remain to be defined, has been referred to in the transfusion medicine literature as ABT-related immunomodulation (TRIM). 11,12

Perioperative blood transfusion and outcome

As a result of advances in pathogen testing and transfusion standards over the last decade, the risk of disease transmission through allogeneic blood transfusions has decreased markedly. The effects of allogeneic blood transfusions on the immune system, however, have received more attention, as they appear to influence outcome. The following review summarizes the effects of allogeneic blood transfusions on selected outcome parameters and the influence of white blood cell reduction on these parameters. Adverse effects of allogeneic blood transfusions on outcome variables such as postoperative infection, cancer recurrence, pulmonary function, length of stay, and mortality have been shown in multiple trials, but most were not randomized or blinded. One proposed approach to reduce unwanted side-effects is to reduce the donor's white blood cell count before transfusion. This can be done either by individual bedside filtration or by pre-storage (or post-storage) universal white blood cell reduction. Studies investigating this approach have yielded conflicting results. Although the results of a number of studies suggest a negative impact of allogeneic blood transfusions on immune function and consequently outcome parameters, this has not been proven in rigorously controlled randomized trial, or in meta-analyses. Reduction of white blood cells might be beneficial in selected patient populations, but at this time does not appear warranted in the general surgical population. As universal white blood cell reduction is a very costly process, it probably should not be implemented until such a benefit is proven.

Pulmonary adenocarcinoma is associated with poor long term survival after surgical resection: effect of allogeneic blood transfusion

PURPOSE: The significance of allogeneic blood transfusion in the prognosis of patients with non small lung cancer (NSCLC) remains controversial. There are reports to suggest that patients with adenocarcinoma (AdenoCa) have a worse prognosis from cancer than patients with squamous cell carcinoma (SCC) but this evidence is lacking in NSCLC. The objective of the current study was to elucidate the correlation between peri-operative allogeneic blood transfusion and the prognosis in patients with AdenoCa and SCC.

Interaction of splenectomy and perioperative blood transfusions on prognosis of patients with proximal gastric and gastroesophageal junction cancer.

To assess the interaction of splenectomy and perioperative allogeneic blood transfusions on the prognosis of patients undergoing a potentially curative resection of proximal gastric and gastroesophageal junction (GEJ) cancer, because reports from the transplantation literature demonstrated that the immunosuppressive effects of transfusions are dependent on the presence of an intact spleen. Between July 1, 1985, and July 30, 2001, 240 patients underwent complete resection (R0) of a proximal gastric or GEJ cancer (Siewert type II or III). Clinical and pathologic factors were collected in a prospective database. The survival data were modeled using the method of Kaplan and Meier and analyzed by the log-rank test and Cox regression. The median follow-up of the patients was 25 months (40 months for survivors). The median relapse-free survival was 30 months, and the median disease-specific survival was 45 months. Univariate analysis suggested an interaction of splenectomy and perioperative transfusion in their effect on relapse-free survival. Patients who received a perioperative transfusion but did not undergo splenectomy demonstrated the worst prognosis on multivariate analysis independent of other prognostic factors. In patients who underwent splenectomy, perioperative transfusion had no effect on relapse-free survival on multivariate analysis. Our study suggests an interaction of blood transfusion and splenectomy in their effect on survival paralleling the findings in the transplantation literature. The adverse effect of allogeneic blood transfusion on prognosis in patients with gastric cancer seems to be associated with the presence of an intact spleen and is abrogated by its absence.

Exposure to allogeneic plasma and risk of postoperative pneumonia and/or wound infection in coronary artery bypass graft surgery.

A relationship may exist between the immunomodulatory effects of allogeneic blood transfusion and the volume of transfused allogeneic plasma and/or the number of transfused plasma-containing units. The records of 416 consecutive patients undergoing coronary artery bypass graft operations at the Massachusetts General Hospital were reviewed. Exposure to allogeneic plasma in units of transfused RBCs, platelets, FFP, and cryoprecipitate was recorded, and diagnoses of postoperative pneumonia and wound infection were made by CDC criteria. The association between postoperative infection and exposure to allogeneic plasma was calculated by logistic regression analyses adjusting for the effects of confounding factors that related to severity of illness, difficulty of operation, and risk of postoperative pneumonia. Two hundred seventy-four patients received (mean +/- SE) 636.2 +/- 64.3 mL of allogeneic plasma, contained in 8.5 +/- 0.7 units of blood components. Sixty-four patients (15.4%) developed pneumonia and/or wound infection, and 54 (13.0%) developed pneumonia. Patients who did (n = 64) or did not develop infection received 956.6 +/- 180.6 and 321.3 +/- 39.6 mL of plasma, respectively (p<0.0001). In multivariate analyses, the volume of transfused allogeneic plasma was not associated with postoperative pneumonia and/or wound infection (p = 0.24), pneumonia (p = 0.21), or wound infection (p = 0.74). Similarly, the number of transfused plasma-containing units was not associated with these outcomes (p = 0.08, p = 0.08, and p = 0.46, respectively). A relationship between the exposure to allogeneic plasma and the risk of postoperative pneumonia and/or wound infection was not detected in this study population.

In vitro immunosuppressive activity of soluble HLA class I and Fas ligand molecules: do they play a role in autologous blood transfusion?

The immunomodulatory effects of allogeneic blood transfusion may contribute to a poor prognosis in patients with cancer who are undergoing surgery, and clinical trials have been carried out to investigate whether these patients would benefit from autologous blood donation. As the immunomodulatory effects of allogeneic blood transfusion have been related to soluble molecules released from residual WBCs during storage, the in vitro immunomodulatory activity of soluble molecules detected in supernatants from stored autologous blood was evaluated. Blood was donated by four healthy volunteers. Packed WBC-reduced RBCs were obtained and stored for 30 days, and supernatants were collected. FFP and serum were also obtained. The concentration of soluble molecules was determined by immunoenzymatic assays. The in vitro immunomodulatory activity of undiluted blood component supernatant was assessed by antigen-specific cytotoxic T-cell activity and mixed lymphocyte reactions in autologous combinations and by apoptosis induction in Fas+ cells. The concentrations of soluble Fas-ligand and HLA class I molecules were higher in packed RBCs than in WBC-reduced RBCs, FFP, and serum. Undiluted supernatants of packed RBCs strongly inhibited functional assays and induced apoptosis in Fas+ cells. The immunomodulatory effects were correlated with the amount of soluble Fas ligand and HLA class I molecules. The results of the present study are comparable with those already reported in allogeneic blood components, and they indicate that undiluted supernatants of autologous blood components may exert immunosuppressive effects in vitro.

Isolated reduction of haematocrit does not compromise in vitro blood coagulation.

Low haematocrit values are generally well tolerated in terms of oxygen transport but a low haematocrit might interfere with blood coagulation. We thus sampled 60 ml of blood in 30 healthy volunteers. The blood was centrifuged for 30 min at 2000 g and separated into plasma, which contained the platelet fraction, and packed red blood cells. The blood was subsequently reconstituted by combining the entire plasma fraction with a mixture of packed red blood cells, 0.9% saline, so that the final haematocrit was either 40, 30, 20, or 10%. Blood coagulation was assessed by computerized Thrombelastograph analysis. Data were compared using repeated measures analysis of variance and post-hoc paired t-tests with Bonferroni correction. Decreasing the haematocrit from 40 to 10% resulted in a shortening of reaction time (r) and coagulation time (k), and an increase in angle alpha, maximum amplitude (MA) and clot strength (G) (all P<0.02). This pattern represents acceleration of blood coagulation with low haematocrit values. The isolated reduction in haematocrit, therefore, does not compromise in vitro blood coagulation.

Large volume apheresis of autologous plasma and preparation of autologous fibrin glue from the plasma.

Autologous blood transfusion (ABT) is useful for prevention of undesirable effects of allogeneic blood transfusion. In our hospital, not only autologous whole blood but also autologous red blood cells, autologous fresh frozen plasma (Auto-FFP), and autologous fibrin glue (Auto-FG) are routinely produced for surgical patients. The Auto-FG is prepared from plasma which is separated from manually collected whole blood. However, when a large volume of Auto-FG is required, the plasma obtained by an apheresis method may be useful. Therefore, a pilot study was conducted to determine whether a collection of 2 U (160 ml) of red blood cells (RBCs) and 400 ml of plasma at 1 apheresis is acceptable. We first performed the apheresis on healthy donors, and then applied for autologous blood donation. The apheresis is safe. The collected plasma is used for the production of Auto-FFP and Auto-FG. The remaining RBCs also are used for ABT. The preparation of Auto-FG is simple, and it is effective for the reduction of allogeneic fibrin glue.

Book Reviews

Immunomodulatory Effects of Blood Transfusion. Edited by Eleftherios C. Vamvakas and Morris A. Blajchman. AABB Press, Bethesda, MD, USA, 1999. Pp. 295. ISBN: 1-56395-110-X. Currently, the most controversial and most widely discussed aspect of blood transfusion is the immunomodulatory effects of the transfusion of blood and blood components. Now that the effects of viral and other microbial agents are sufficiently mapped and understood, scientific and political attention focuses on the possible and thinkable effects of white blood cells in human blood components for transfusion. This book provides a comprehensive and critical review of the scientific state of the art, recognizing that such states of the art do change in a very dynamic manner. It is also recognized that there are disappointingly few hard scientific data, but an overwhelming variety of hypotheses and scientific assumptions that bear the risk of easy extrapolation in the ‘totum pro partum’ principle. The first two chapters deal with the history of the immunomodulation concept and the complexity of the human immune response. Chapters 3–5 provide animal experimental data on the effects of blood transfusion in relation to tumour growth, organ transplantation and risk of infection. Chapter 6 provides insight on proposed mechanisms of immunomodulatory effects of allogeneic blood transfusion, bringing the book to the paramount point of interpretation of findings of published clinical studies of the immunomodulatory effects of blood transfusion. This chapter is probably the most important part of the book, written by one of the exclusive experts in the field of meta-analysis, statistical evaluation and interpretation of rationale, objectives and findings of such studies. This chapter is followed by three chapters on the most relevant clinical effects so far discussed: survival of renal transplants, recurrence of cancer and infection. Chapter 11 discusses the possible effects of activation of dormant viruses, in particular CMV and HIV, besides valuable remarks on the immune effects of chronic exposure to clotting factor concentrates in patients with haemophilia. Chapter 12 adds some information on debatable clinical conditions related to blood transfusion, such as recurrent abortion and rheumatoid arthritis. The editors, reinforced by one of the expert panel members, conclude the book with an attempt to appraise the available evidence of deleterious effects of transfusion-associated immunomodulation and some recommendations for prevention. There is a balanced, although somewhat provocative, discussion on the pros and cons of the public policy-determined universal leucocyte depletion in the summary. All three authors share the belief that an adverse immunomodulatory effect of allogeneic blood transfusion probably exists, but also believe that such an effect is of modest magnitude. They argue that because of the small magnitude of the effect and the strong relationship between the need for transfusion and illness severity, it has been difficult to document the existence of this effect after adjusting appropriately for confounding factors. Therefore, the authors plead strongly for continuation of well-conducted, preferably double-blind, investigations of the purported deleterious immunomodulatory effects of allogeneic blood transfusions, beside the need for critical cost-benefit evaluation with respect to quality of life gained. The book is recommended as an important reference to determine the actual and future scientific ‘state of the art’ in immunomodulatory effects of allogeneic blood transfusion.

Mechanisms and new approaches for the allogeneic blood transfusion-induced immunomodulatory effects

ELLULAR BLOOD components such as red cells, platelets, and granulocytes are routinely used for clinical conditions associated with deficits of these respective cells in patients. Because different alloantigens are present on donor blood cells, elicitation of humoral and cellular immune responses to these foreign antigens is expected. These immune responses could lead to various types of transfusion reactions, such as hemolysis, fever, lung injury, refractoriness to random donor platelets, and so forth. ~ In addition to these well-recognized immunologic reactions, a number of unintended and subtle immunologic consequences associated with transfusions of allogeneic blood components have also been reported. The best-documented consequence is the prolonged survival of renal allografts in patients who had blood transfusions before transplantation. 2,3 This finding indicates that allogeneic blood transfusion could enhance the acceptance of allografts and has prompted extensive investigation on the possible immunologic mechanisms for this intriguing phenomenon. 4 This finding also prompted a close examination of other possible clinical consequences that might have resulted from potential nonspecific immunosuppressive effect of allogeneic blood transfusion. The reported clinical consequences include increased risk of postoperative infection, 5,6 increased growth and dissemination of tumor cells] activation of latent viral infection, 8-1~ amelioration of immune inflammatory diseases,11 and prevention of recurrent spontaneous abortions. ~2,13 However, the causal association between these immunologic effects and allogeneic blood transfusion remains controversial, and the mechanisms for these effects are poorly defined. 13-15 Recent advances in the

Prestorage versus poststorage white cell reduction for the prevention of the deleterious immunomodulatory effects of allogeneic blood transfusion

ECENTLY, the United Kingdom, Ireland, and Portugal announced plans to implement universal white blood cell (WBC) reduction of all transfused allogeneic cellular blood components to prevent the theoretical risk of transmission of new variant Creutzfeldt-Jakob disease (nvCJD) by transfusion. 1 France and Canada also announced plans to implement universal WBC reduction to enhance overall transfusion safety. Universal WBC reduction will confer 3 proven and several potential benefits to patients. The proven benefits are the prevention of alloimmunization to human leukocyte antigens; the prevention of transmission of cytomegalovirus (CMV); and the prevention of febrile, nonhemolytic transfusion reactions (FNHTR). z The potential benefits include the prevention of the deleterious effects of transfusionassociated immunomodulation 3-5 and of virus activation6; the reduction of the risk of transfusionassociated bacterial sepsis7; the prevention of transmission of leukotropic viruses other than CMV2; as well as the prevention of the theoretical risk of transmission of the agent of nvCJD by transfusion.1 The risk of transmission of nvCJD by transfusion is considered only a theoretical possibility currently in the United States, because a bovine spongioform encephalopathy epidemic in cattle and cases of nvCJD have not occurred in North America. Therefore, if a decision were to be made to implement universal WBC reduction in the United States, such a policy would probably be introduced not with an intent to prevent the transmission of nvCJD, but to reap other potential benefits from WBC reduction. Most of the published evidence regarding other potential benefits pertains to the prevention of the deleterious immunomodulatory effects of allogeneic transfusion, 3-5 and the public debate regarding the implementation of universal WBC reduction in the United States is likely to focus on an examination of the efficacy and cost-effectiveness of WBC reduction in preventing these potential adverse effects.

Autoapheresis and intraoperative blood salvage in oncologic surgery

Transfusion of predeposit or salvaged autologous blood has continued to grow since the 1980s. Issues such as the indications for use and cost effectiveness as well as the safety of autologous blood salvaged during cancer surgery have emerged and should be addressed. The concern for possible contamination of autologous RBC with cancer cells responsible for metastasis has limited the use of autologous salvaged blood in cancer patients. Nevertheless, clinical experience has been gained on the use of salvaged blood in patients with colorectal, gastric, renal, hepatic, breast, bladder and lung cancer. No evidence has been reported showing an increase in metastasis or a decrease in patient survival, in spite of the obvious demonstration that salvaged blood is contaminated with viable tumor cells which are not washed out of the RBC layer during intraoperative blood salvage (IOBS). However, a number of limitations have hampered the widespread use of IOBS in these patients and the technique is not well established. Increasing knowledge of the deleterious effects of allogeneic blood transfusion both in terms of the increased number of viral or bacterial infections and the down-regulation of the patient's immune system have recalled attention to IOBS and to the techniques such as filtration, which might reduce the risk of reinfusion of cancer cells, or totally eliminate the risks such as irradiation has been proposed by Hansen’s group. This paper reviews the topic with some emphasis on our personal experience with γ and X-ray irradiation of salvaged blood in a large reference hospital, where IOBS and filtration of salvaged blood were established for use in cancer patients in 1993 and 1996.

Press Review

Soluble HLA Class I, HLA Class II and Fas Ligand in Blood Components: A Possible Key to Explain the Immunomodulatory Effects of Allogeneic Blood Transfusion

Risk of bacterial infection associated with allogeneic blood transfusion among patients undergoing hip fracture repair.

The relationship between allogeneic blood transfusion and bacterial infection remains uncertain. An increased risk of bacterial infection would represent the most important risk of allogeneic transfusion, because viral disease transmission has become so rare. A retrospective cohort study of 9598 consecutive hip fracture patients at least 60 years old who underwent surgical repair was performed. The primary outcome was serious bacterial infection, defined as bacteremia, pneumonia, deep wound infection, or septic arthritis or osteomyelitis. Secondary outcomes included two individual infections, pneumonia and urinary tract infection (UTI), and the cost of infection. Hospital cost of infection was assessed by linking the study population to Medicare data. Fifty-eight percent of patients received at least one transfusion. Serious bacterial infection occurred in 437 patients (4.6%); 28.8 percent of this group died during the hospital stay. Pneumonia occurred in 361 patients (3.8%) and UTI occurred in 1157 patients (12.1%). The adjusted risk of serious bacterial infection associated with transfusion was 1.35 (95% CI, 1.10-1.66). The adjusted risk for pneumonia was 1.52 (95% CI, 1.21-1.91), and that for UTI was 1.03 (95% CI, 0.91-1.17). A dose-response relationship was present for serious bacterial infection (p = 0.001) and pneumonia (p = 0.001). The cost of hospitalization was $14,000 greater for patients with serious infection than for patients without infection. Blood transfusion is associated with a 35-percent greater risk of serious bacterial infection and a 52-percent greater risk of pneumonia. Postoperative infections are costly. The risk of bacterial infection may be the most common life-threatening adverse effect of allogeneic blood transfusion.

Soluble HLA Class I, HLA Class II, and Fas Ligand in Blood Components: A Possible Key to Explain the Immunomodulatory Effects of Allogeneic Blood Transfusions

AbstractThe immunomodulatory effect of allogeneic blood transfusions (ABT) has been known for many years. However, a complete understanding of the effects of ABT on the recipient's immune system has remained elusive. Soluble HLA class I (sHLA-I), HLA class II (sHLA-II), and Fas ligand (sFasL) molecules may play immunoregulatory roles. We determined by double-determinant immunoenzymatic assay (DDIA) sHLA-I, sHLA-II, and sFasL concentrations in different blood components. sHLA-I and sFasL levels in red blood cells (RBCs) stored for up to 30 days and in random-donor platelets are significantly (P < .001) higher than in other blood components and their amount is proportionate to the number of residual donor leukocytes and to the length of storage. Blood components with high sHLA-I and sFasL levels play immunoregulatory roles in vitro as in allogeneic mixed lymphocyte responses (MLR) and antigen-specific cytotoxic T-cell (CTL) activity, and induce apoptosis in Fas-positive cells. These data suggest that soluble molecules in blood components are functional. If these results are paralleled in vivo, they should be taken into account in transfusion practice. Blood components that can cause immunosuppression should be chosen to induce transplantation tolerance, whereas blood components that lack immunosuppressive effects should be preferred to reduce the risk of postoperative complications and cancer recurrence.

Soluble HLA Class I, HLA Class II, and Fas Ligand in Blood Components: A Possible Key to Explain the Immunomodulatory Effects of Allogeneic Blood Transfusions

The immunomodulatory effect of allogeneic blood transfusions (ABT) has been known for many years. However, a complete understanding of the effects of ABT on the recipient's immune system has remained elusive. Soluble HLA class I (sHLA-I), HLA class II (sHLA-II), and Fas ligand (sFasL) molecules may play immunoregulatory roles. We determined by double-determinant immunoenzymatic assay (DDIA) sHLA-I, sHLA-II, and sFasL concentrations in different blood components. sHLA-I and sFasL levels in red blood cells (RBCs) stored for up to 30 days and in random-donor platelets are significantly (P <.001) higher than in other blood components and their amount is proportionate to the number of residual donor leukocytes and to the length of storage. Blood components with high sHLA-I and sFasL levels play immunoregulatory roles in vitro as in allogeneic mixed lymphocyte responses (MLR) and antigen-specific cytotoxic T-cell (CTL) activity, and induce apoptosis in Fas-positive cells. These data suggest that soluble molecules in blood components are functional. If these results are paralleled in vivo, they should be taken into account in transfusion practice. Blood components that can cause immunosuppression should be chosen to induce transplantation tolerance, whereas blood components that lack immunosuppressive effects should be preferred to reduce the risk of postoperative complications and cancer recurrence.

Immune Response and Cytokines in Septic Rats Undergoing Blood Transfusion

Background.Intrabdominal sepsis and allogeneic blood transfusion have been associated with a depression of the immune response in patients undergoing surgery. Some authors have considered that an already immunocompromised host is probably primed for a potential detrimental effect of allogeneic blood. The aim of this paper is to ascertain the effects of allogeneic blood transfusion on the lymphocyte subsets and cytokines in septic rats.Materials and Methods.Thirty rats were allotted into three groups: Sham-CLP, anesthesia and laparotomy; CLP, cecal ligation and puncture; CLP+BT, CLP and allogeneic blood transfusion. Preoperatively and on the 1st, 3rd, and 7th postoperative days, the cell percentages of lymphocyte subpopulations, the IL-2 receptor expression, and the IL-1, IL-2, TNF-α and IFN-γ were measured in blood by flow cytometry and ELISA.Results.CLP+BT rats showed on Day 3 a decrease of the CD4+%, an increase of the IL-2R expression directly correlated to the increase of the CD8+% phenotype, a steady increase of IL-1 levels, a decrease of the TNF-α levels on the 1st and 3rd days, and a decrease of the IL-2 and IFN-γ on Day 1.Conclusions.An accumulative effect of the immunodepression induced by sepsis was observed when allogeneic blood transfusion is added. Blood transfusion + sepsis induces an extensive impairment on cellular immune response and an initial cytokine downregulation, except for IL-1.