Immunomodulation Effect of Blood Transfusion

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

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.

Study Overview

• Status: Completed
• Conditions: Surgery; Immune Defect; Incompatible Blood Transfusion
• Intervention / Treatment: Biological: Day 0 blood transfusion; Biological: Day 1 or 2 blood transfusion; Biological: No blood transfusion

Detailed Description

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 Additionally withdrawn samples currently not used for analysis will stored for further studies.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.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10700
    • Faculty of Medicine Siriraj Hospital, Mahidol University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing elective spine surgery/

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Day 0 blood transfusion; Patients undergoing elective spine surgery receiving intra- or immediate-postoperative red cell blood transfusion.	Biological: Day 0 blood transfusion; Patients undergoing elective spine surgery receiving intra- or immediate-postoperative red cell blood transfusion.
Day 1 or 2 blood transfusion; 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; Patients undergoing elective spine surgery receiving first red cell blood transfusion on day 1 or 2 after surgery.
No blood transfusion; Patients undergoing elective spine surgery receiving no blood transfusion.	Biological: No blood transfusion; No blood transfusion

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mahidol University
• Collaborators: Wolf Schleinzer Stiftung zur Wissenschafts- und Bildungsförderung, Germany
• Investigators: Study Director: Sirilak Suksompong, MD, Mahidol University

Publications and helpful links

General Publications

• Marik PE, Corwin HL. Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature. Crit Care Med. 2008 Sep;36(9):2667-74. doi: 10.1097/CCM.0b013e3181844677. Erratum In: Crit Care Med. 2008 Nov;36(11):3134.
• von Bormann B, Wirtz S, Weiler J, von Bormann C, Trobisch H. [Quality of whole blood as a result of storage and preparation (inline-leukocyte depletion). Evidence for autologous predeposit]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2000 May;35(5):326-32. doi: 10.1055/s-2000-323. German.
• Ghio M, Contini P, Negrini S, Mazzei C, Zocchi MR, Poggi A. Down regulation of human natural killer cell-mediated cytolysis induced by blood transfusion: role of transforming growth factor-beta(1), soluble Fas ligand, and soluble Class I human leukocyte antigen. Transfusion. 2011 Jul;51(7):1567-73. doi: 10.1111/j.1537-2995.2010.03000.x. Epub 2011 Jan 7.
• Leal-Noval SR, Munoz-Gomez M, Arellano V, Adsuar A, Jimenez-Sanchez M, Corcia Y, Leal M. Influence of red blood cell transfusion on CD4+ T-helper cells immune response in patients undergoing cardiac surgery. J Surg Res. 2010 Nov;164(1):43-9. doi: 10.1016/j.jss.2009.03.010. Epub 2009 Apr 18.
• Heiss MM, Fasol-Merten K, Allgayer H, Strohlein MA, Tarabichi A, Wallner S, Eissner HI, Jauch KW, Schildberg FW. Influence of autologous blood transfusion on natural killer and lymphokine-activated killer cell activities in cancer surgery. Vox Sang. 1997;73(4):237-45. doi: 10.1046/j.1423-0410.1997.7340237.x.
• Suksompong S, Tassaneetrithep B, Ariyawatkul T, Sirivanasandha B, Wilartratsami S, Wongsa A, von Bormann B. Allogeneic red cell transfusion and its influence on relevant humoral and cellular immunological parameters: A prospective observational trial. Eur J Anaesthesiol. 2019 Nov;36(11):814-824. doi: 10.1097/EJA.0000000000001027.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2014
• Primary Completion (ACTUAL): June 18, 2017
• Study Completion (ACTUAL): April 10, 2018

Study Registration Dates

• First Submitted: May 5, 2014
• First Submitted That Met QC Criteria: May 12, 2014
• First Posted (ESTIMATE): May 16, 2014

Study Record Updates

• Last Update Posted (ACTUAL): September 8, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Surgery; Immune; Blood transfusion
• Other Study ID Numbers: Si 081/2557 (EC3)