Immunomodulation Effect of Blood Transfusion

Surgery Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02140216
• Other study ID #: Si 081/2557 (EC3)
• Status: Completed
• Start date: May 2014
• Est. completion date: April 10, 2018

Study information

• Verified date: August 2021
• Source: Mahidol University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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 Additionally withdrawn samples currently not used for analysis will stored for further studies.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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 10, 2018
• Est. primary completion date: June 18, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Immune Defect
• Incompatible Blood Transfusion
• Surgery

Intervention

Biological:
• No blood transfusion
No blood transfusion
• 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.

Locations

Country	Name	City	State
Thailand	Faculty of Medicine Siriraj Hospital, Mahidol University	Bangkok

Sponsors (2)

Lead Sponsor	Collaborator
Mahidol University	Wolf Schleinzer Stiftung zur Wissenschafts- und Bildungsförderung, Germany

Country where clinical trial is conducted

Thailand, 

References & Publications (5)

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-ß(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. — View Citation

Heiss MM, Fasol-Merten K, Allgayer H, Ströhlein 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. — View Citation

Leal-Noval SR, Muñoz-Gómez M, Arellano V, Adsuar A, Jiménez-Sánchez 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. — View Citation

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. Review. Erratum in: Crit Care Med. 2008 Nov;36(11):3134. — View Citation

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. German. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Macrophage inflammatory protein 1 alpha (MIP-1a)	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	macrophage inflammatoryprotein 1 beta (MIP-1b)	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	platelet-derived growth factor-BB	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	RANTES	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	tumour TNF alpha	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	VEGF	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	Ferritin	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	Fibrinogen	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	procalcitonin	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	interleukin	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	basic fibroblast growth factor (B-FGF)	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	eotaxin (monocyte chemotactic proteins)	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	G-CSF	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	GM-CSF	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	IFN-alpha	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	IP-10	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	MCP-1	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	MCAF	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	serum amyloid A	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	tissue plasminogen activator	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Primary	Postoperative non-surgical complications	Infection, thrombosis, pulmonary affection	30 days
Secondary	CD2 Cellular immunologic parameter (non-radioisotope),	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Secondary	CD3 Cellular immunologic parameter (non-radioisotope),	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Secondary	CD4 Cellular immunologic parameter (non-radioisotope),	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Secondary	CD 8 Cellular immunologic parameter (non-radioisotope),	preoperative, postoperative day 1, 3, 5	5 days
Secondary	CD 8 Cellular immunologic parameter (non-radioisotope),	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Secondary	CD 25 Cellular immunologic parameter (non-radioisotope),	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Secondary	CD 30 Cellular immunologic parameter (non-radioisotope),	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Secondary	CD 19 Cellular immunologic parameter (non-radioisotope),	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Secondary	CD 20 Cellular immunologic parameter (non-radioisotope),	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Secondary	CD 138 Cellular immunologic parameter (non-radioisotope),	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Secondary	CD 56 Cellular immunologic parameter (non-radioisotope),	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Secondary	CD 303 Cellular immunologic parameter (non-radioisotope),	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Secondary	CLT cytotoxicity (non-radioisotope),	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Secondary	CD 304	Blood sample on preoperative, postoperative day 1, 3, 5	5 days
Secondary	NK cytotoxicity	Blood sample on preoperative, postoperative day 1, 3, 5	5 days