Immunosuppressive Effect Of Blood Transfusion Research Articles

Perioperative Blood Transfusion and Postoperative Outcome in Patients with Crohn’s Disease Undergoing Primary Ileocolonic Resection in the “Biological Era”

BackgroundPerioperative blood transfusion has been shown to be associated with inflammatory response and immunosuppression. Patients receiving blood transfusion may have an increased risk for developing postoperative morbidities. The impact of blood transfusion on the postoperative recurrence of Crohn’s disease (CD) has been controversial. The aim of this study was to assess the effect of blood transfusion on postoperative outcomes in CD in the current biological era. MethodsThis historical cohort study involved data collection and analysis of CD patients who underwent the index ileocolonic resection in our institution between 2000 and 2012. Postoperative complications were compared between the transfused and nontransfused patients. The effects of perioperative blood transfusion on postoperative complications and disease recurrence were analyzed with both univariate and multivariate analyses. ResultsA total of 318 patients were included in the study, and 52 of them (16.5 %) received perioperative blood transfusion. Blood transfusion was found to be associated with an increased risk of postoperative infectious and noninfectious complications both in univariate (P < 0.001 for each) and multivariable analyses (infectious complications: odds ratio [OR] = 8.73, 95 % confidence interval [CI] 2.85–26.78, P < 0.001; noninfectious complications: OR = 3.64, 95 % CI 1.30–10.18; P = 0.014). In addition, the Cox regression model indicated that blood transfusion was associated with both surgical (hazard ratio [HR] = 3.43, 95 % CI 1.92–6.13; P < 0.001) and endoscopic (HR = 2.08, 95 % CI 1.38–3.14; P < 0.001) CD recurrence following the index surgery. ConclusionAdverse outcomes after perioperative blood transfusion for the primary ileocolonic resection for CD resemble findings in surgery for other diseases. The presumed immunosuppressive effect of blood transfusion did not confer any protective effect on disease recurrence.

Blood transfusions in the surgical patient: A gift of life, but at what cost?

DOI of original article: 10.1016/j.jss.2012.0 * Corresponding author. Department of Surge 2M, New York, NY 10003. Tel.: 212 844 8570; E-mail address: mleitman@chpnet.org (I. 0022-4804/$ e see front matter a 2013 Elsev doi:10.1016/j.jss.2012.02.031 From the discovery of circulation by Dr. William Harvey in 1628, to the first successful human-to-human blood transfusion by Dr. James Blundell in 1818, to the creation of the American Red Cross in 1941, our understanding of blood transfusion has evolved. The so-called hazards of transfusions have been documented since World War II and include infectious complications, hemolytic-related reactions, and, in more recent times, transfusion-related lung injuries and transfusion-induced immunomodulation [1,2]. This immunologic consequence of blood transfusions is not a novel concept. During the 1970s, the immunosuppressive effects of blood transfusion were first recognized when Opelz and Teraski [3] reported improvement in kidney transplant graft survival with an increased number of blood transfusions. This landmark study was the first to highlight the pro-inflammatory and immunosuppressive effects of transfused blood. Despite these

Blood transfusion and recurrence of colorectal cancer: The role of platelet derived growth factors

Efforts to explain the possible effects of blood transfusion on the recurrence of colorectal cancer have been based entirely on the immunosuppressive effects of blood transfusion. However, the relationship between solid tumour development and the immune system is inconclusive. We have investigated an alternative mechanism involving the potential role of growth factors in this phenomenon. Using a human fibroblast: [125I]deoxyuridine uptake mitogenesis assay, the relative amounts of growth factor in the plasma of stored blood were measured. There was a progressive increase in mitogenesis from day 0 (n = 6) to day 28 (n = 6; P less than 0.001, Mann-Whitney U test). The effect of growth factors on the development of liver and intraperitoneal metastases was studied in Hooded Lister rats. Following an intraportal injection of 10(5) MC28 tumour cells, the experimental group (n = 25) received 2 ml of syngeneic serum intravenously for 4 days. Likewise, colonic anastomoses were performed on omentectomized rats and the peritoneal cavity seeded with 10(3) cells. The experimental groups (n = 20) received either 2 ml serum intravenously repeatedly or 3 ml serum intraperitoneally (n = 19). There was no significant increase in liver metastases or peritoneal disease following intravenous infusion of serum but serum delivered intraperitoneally resulted in a significant increase in tumour from 22 per cent in the controls to 89 per cent in the study group (P less than 0.01). Growth factors released from platelets following blood loss into the peritoneal cavity may be important in enhancing local recurrence of colorectal cancer.

Immune responsiveness in orthopedic surgery patients after transfusion of autologous or allogeneic blood

The proposed immunosuppressive effect of blood transfusion is not yet understood, and the clinical relevance is a controversial topic of discussion. The effect of blood transfusions on the capacity of the host's immunocompetent cells to react to mitogenic stimulation was evaluated. Patients undergoing hip replacement surgery received either allogeneic (n = 13) or autologous (n = 14) buffy coat-depleted red cells or plasma. Patients' blood samples taken before and on Days 1 and 5 after surgery were stimulated in a whole-blood assay. The release of interleukin 2, soluble interleukin 2 receptor, interleukin 6, tumor necrosis factor alpha, interferon alpha 2, and interferon gamma was assessed by enzyme-linked immunosorbent assay. In addition, the white cell counts and frequencies of the lymphocyte subsets CD4+, CD8+, and natural killer cells were analyzed. For both groups, decreased levels of interleukin 2 and interferon-gamma were detected postoperatively, whereas the values for soluble interleukin 2 receptor and tumor necrosis factor alpha showed no significant change. Interferon alpha 2 was decreased on Day 1, but returned to normal by Day 5. Interleukin 6 increased during the time of observation. There were no significant differences between the two groups in cytokine production and lymphocyte-subset analysis that could be attributed to the transfusion of allogeneic blood. The transfusion of buffy coat-depleted red cells showed no immediate suppressive effect on the immune function of the host's peripheral blood cells.

Immunosuppressive Effects of Blood Transfusion

Various in vitro studies, animal models, and retrospective investigations suggest that blood transfusion modulates the immune system. Not all studies, however, support this trend. This article provides a balanced presentation of the issues surrounding the concept of the immunosuppressive effects of blood transfusion.

The Immunosuppressive Aspects of Blood Transfusion

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.

Analysis of local recurrence of midrectal cancer after low anterior resection and stapled anastomosis.

We evaluated local recurrences of midrectal cancer in 33 patients treated with low anterior resection and stapled end-to-end anastomosis. All patients had follow-up for at least 2 years or until death. There were 21 men and 12 women. Data were analyzed with attention to Astler-Coller modified Dukes' stage, distal margin of resection, degree of histologic differentiation, location of the tumor, blood transfusion, and adjuvant therapy. Distal margin of resection, histologic differentiation, and location of the tumor had no prognostic significance regarding local recurrence. The use of adjuvant therapy remains controversial. The immunosuppressive effects of blood transfusion may affect local recurrence. Dukes' staging remains the standard for prognosis of recurrence in rectal cancer.

Transfusion-induced immunosuppression and red cell clearance.

While blood transfusion is increasingly implicated in the aetiology of tumour recurrence, the mechanism of this effect is unclear. Cancer-bearing patients are known to have factors in their sera which depress the function of normal lymphocytes. It is possible that blood transfusion accentuates this natural suppression. An animal model was therefore developed to study the effect of blood transfusion on humoral immunosuppressive activity and its possible relationship to red cell clearance. WAG rats given a transfusion of chromium-labelled allogeneic but blood-group compatible DA rat blood, developed significantly increased (P < 0.001) levels of lymphocyte suppressive factors in plasma (maximum at 7 days) which coincided with accelerated red cell clearance (t1/2 = 7 days). A transfusion of syngeneic WAG blood caused only a small transient increase in plasma suppression and red cells were cleared at a normal rate (t1/2 = 13 days) consistent with previous studies. However, when syngeneic WAG red cells were lysed and the red cell membranes infused there was a rapid increase in plasma suppression (P < 0.001), similar to but less prolonged than that achieved with allogeneic blood. The immunosuppressive effect of blood transfusion may result from accelerated clearance of allogeneic or damaged syngeneic red blood cells.

EFFECT OF PERIOPERATIVE BLOOD TRANSFUSION ON RECURRENCE OF CROHN'S DISEASE

The effect of perioperative blood transfusion on recurrence of Crohn's disease was investigated retrospectively in 60 patients with Crohn's disease who underwent small-bowel resection. 28 patients received 1-8 units of blood; the others were not transfused. Both groups were similar in age, duration of Crohn's disease, and preoperative serum albumin, but preoperative haemoglobin, length of intestine resected, and location of small-bowel involvement were different. The patients who received perioperative blood transfusion had a significantly lower recurrence rate by life-table analysis, although the site and greater length of bowel involvement in the transfused patients would normally indicate an increased likelihood of recurrence. 5 years after bowel resection, the cumulative recurrence rate in transfused patients was 19%, compared with 59% in controls. The immunosuppressive effect of blood transfusion may modify the progression of Crohn's disease.

EFFECT OF BLOOD TRANSFUSION ONSURVIVAL AFTER SURGERY OF LUNG CANCER

The immunosuppressive effects of blood transfusion in renal transplantation patients are well-known. We investigated as to the relationship between perioperative blood transfusion and survival after surgery of lung cancer. One hundred fifty patients undergoing surgery for lung cancer were analysed retrospectively. The cumulative survival rates for 5 years were 48.8% in those with no transfusion as opposed to 30.2% in those who had been transfused. In patients with Stage I or Stage II and III, transfused patients had lower 5-year-survival rates than nontransfused patients (62.5% versus 69.3% or 6.5% versus 30.8). especially in 71 patients who had undergone lobectomy, the 5-year-survival rate was significantly worse for those who had been transfused (49.8%) than for those who had not been transfused (75.0%) (p<0.05). Therefore perioperative blood transfusion adversely affects prognosis after resection of lung cancer.

Immunosuppressive effects of blood transfusion in anaesthesia and surgery.

The immunosuppressive effects of blood transfusion at surgical operations become manifest as enhanced graft survival, increased cancer recurrence and decreased patient survival, and increased susceptibility to postoperative infections. Blood transfusion in transplant recipients no longer offers this advantage when cyclosporine A is used. The deleterious effects of blood transfusion on the prognosis of some cancers found in the statistical analyses of retrospective studies are considered to be of increasing clinical importance. Therefore, unnecessary blood transfusions should be avoided and special attention directed to the use of autologous blood. Leucocyte-free red blood concentrates are the least immunosuppressive homologous blood preparations. Conventional red blood cell concentrates may also be used in cancer patients until ongoing prospective randomized studies confirm that there is a true association between the use of homologous blood and increased recurrence of cancer.