Immunomodulation Effect of Blood Transfusion

Study Overview
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Brief Summary
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An increasing number of publications have demonstrated that homologous (allogeneic) blood transfusion impairs outcome in cancer and non-cancer patients. Leukocyte depletion of blood products cannot solve these problems, despite improved quality of red cells; a recent study demonstrated deteriorated outcome of cancer patients with elective colon surgery and transfusion of leukocyte depleted allogeneic blood.

Detailed Description
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All patients undergo the identical anesthesiological procedure, including premedication, general anesthesia with endotracheal intubation, monitoring and postoperative pain therapy and mobilization.Surgery is performed by the identical team performing a standardized technique. Transfusion regimen The 'trigger' for homologous red cell transfusion intra- and postoperatively is the actual hematocrit concentration. Transfusion depends on discretion of the treating physicians. Number of units transfused, amount of blood loss, time, reasoning and decision maker are recorded. Blood samples Within the kind of surgical procedures chosen for this study the chance of red cell transfusion is about 60 - 70%. In terms of figures 10 non-transfused cases could be gained within 40 cases in total. However, transfusion or non-transfusion does not happen in a row. We expect the total number of patients with blood withdrawal to be between 50 and 60. Additionally withdrawn samples currently not used for analysis will stored for further studies. The purpose to include non-transfused otherwise fully comparable patients is to distinguish between trauma (operation) and transfusion and their influence on immune modulation. Within the studies about blood transfusion and immune modulation only some few made this differentiation. In patients with colorectal cancer surgery randomized groups with autologous predonation and patients with allogeneic transfusion only have been compared. However, within the latter (allogeneic) group of 27 patients only 13 had to be transfused, thus creating a non-transfusion group of 14 patients. These 14 non-transfused patients remained within the study being compared with autologous and allogeneic transfused patients. Operative trauma and allogeneic transfusion both increased the secretion of several cytokines including tumor necrosis factor (TNF) alpha and Interleukin-10; this effect was less pronounced in patients with autologous- and without any transfusion. Another group studied forty three orthopedic patients with total knee- or hip-arthroplasty, initially to compare autologous to allogeneic red cell transfusion. They had to change their protocol due to the small number of allogeneic transfusions (8 of 43). Including perioperatively transfused patients only (n = 37) they found an increase in immune regulatory cytokine Interleukin (IL)-10 after red cell transfusion, which was most pronounced 7 days after surgery, whereas there was only a mild increase in non- or autologous transfused patients. Unfortunately they did not differentiate between autologous-and non-transfused patients. Thus their data could not reveal the effect of surgery itself on the analyzed parameters.

Official Title
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Allogeneic Red Cell Transfusion and Its Influence on Relevant Humoral and Cellular Immunological Parameters

Conditions
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Incompatible Blood Transfusion, Immune Defect, Surgery

Intervention / Treatment
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* Biological: No blood transfusion
* Biological: Day 0 blood transfusion
* Biological: Day 1 or 2 blood transfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing elective spine surgery American Society of Anesthesiologist Risk score classification (ASA) I-III Hemoglobin > 9 gm/dL Exclusion Criteria: Patients who have the concomitant condition; cancer, history of heart disease including, heart failure, coronary artery disease, hypertension treated with more than one medicament, serum creatinine > 1.5 mg/dL., stroke, neurologic and mental deficits, epilepsy, general or local infection (site of surgery), coagulation disorders, rheumatoid arthritis. Patients who have one of the following drugs; aspirin, methotrexate, cyclosporin, qualaquin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Day 0 blood transfusion<br>Patients undergoing elective spine surgery receiving intra- or immediate-postoperative red cell blood transfusion. | Biological: Day 0 blood transfusion<br>* Patients undergoing elective spine surgery receiving intra- or immediate-postoperative red cell blood transfusion.<br>|
| Day 1 or 2 blood transfusion<br>Patients undergoing elective spine surgery receiving first red cell blood transfusion on day 1 or 2 after surgery. | Biological: Day 1 or 2 blood transfusion<br>* Patients undergoing elective spine surgery receiving first red cell blood transfusion on day 1 or 2 after surgery.<br>|
| No blood transfusion<br>Patients undergoing elective spine surgery receiving no blood transfusion. | Biological: No blood transfusion<br>* No blood transfusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Macrophage inflammatory protein 1 alpha (MIP-1a) | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| macrophage inflammatoryprotein 1 beta (MIP-1b) | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| platelet-derived growth factor-BB | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| RANTES | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| tumour TNF alpha | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| VEGF | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| Ferritin | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| Fibrinogen | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| procalcitonin | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| interleukin | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| basic fibroblast growth factor (B-FGF) | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| eotaxin (monocyte chemotactic proteins) | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| G-CSF | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| GM-CSF | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| IFN-alpha | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| IP-10 | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| MCP-1 | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| MCAF | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| serum amyloid A | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| tissue plasminogen activator | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| Postoperative non-surgical complications | Infection, thrombosis, pulmonary affection | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD2 Cellular immunologic parameter (non-radioisotope), | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| CD3 Cellular immunologic parameter (non-radioisotope), | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| CD4 Cellular immunologic parameter (non-radioisotope), | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| CD 8 Cellular immunologic parameter (non-radioisotope), | preoperative, postoperative day 1, 3, 5 | 5 days | 
| CD 8 Cellular immunologic parameter (non-radioisotope), | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| CD 25 Cellular immunologic parameter (non-radioisotope), | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| CD 30 Cellular immunologic parameter (non-radioisotope), | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| CD 19 Cellular immunologic parameter (non-radioisotope), | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| CD 20 Cellular immunologic parameter (non-radioisotope), | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| CD 138 Cellular immunologic parameter (non-radioisotope), | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| CD 56 Cellular immunologic parameter (non-radioisotope), | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| CD 303 Cellular immunologic parameter (non-radioisotope), | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| CLT cytotoxicity (non-radioisotope), | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| CD 304 | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 
| NK cytotoxicity | Blood sample on preoperative, postoperative day 1, 3, 5 | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood transfusion, Immune, Surgery