Clinical trial NCT02140216: Immunomodulation Effect of Blood Transfusion
Official title: Allogeneic Red Cell Transfusion and Its Influence on Relevant Humoral and Cellular Immunological Parameters
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Incompatible Blood Transfusion
Immune Defect
Surgery
Keywords: Blood transfusion
Immune
Surgery
Lead sponsor: Mahidol University
Sponsor class: OTHER
Collaborators: name: Wolf Schleinzer Stiftung zur Wissenschafts- und Bildungsförderung, Germany
First posted: 2014-05-16
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients undergoing elective spine surgery/

Brief 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.

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 Additionally withdrawn samples currently not used for analysis will stored for further studies.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

Eligibility criteria: 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

Primary outcomes:
measure: Macrophage inflammatory protein 1 alpha (MIP-1a)
timeFrame: 5 days
measure: macrophage inflammatoryprotein 1 beta (MIP-1b)
timeFrame: 5 days
measure: platelet-derived growth factor-BB
timeFrame: 5 days
measure: RANTES
timeFrame: 5 days
measure: tumour TNF alpha
timeFrame: 5 days
measure: VEGF
timeFrame: 5 days
measure: Ferritin
timeFrame: 5 days
measure: Fibrinogen
timeFrame: 5 days
measure: procalcitonin
timeFrame: 5 days
measure: interleukin
timeFrame: 5 days
measure: basic fibroblast growth factor (B-FGF)
timeFrame: 5 days
measure: eotaxin (monocyte chemotactic proteins)
timeFrame: 5 days
measure: G-CSF
timeFrame: 5 days
measure: GM-CSF
timeFrame: 5 days
measure: IFN-alpha
timeFrame: 5 days
measure: IP-10
timeFrame: 5 days
measure: MCP-1
timeFrame: 5 days
measure: MCAF
timeFrame: 5 days
measure: serum amyloid A
timeFrame: 5 days
measure: tissue plasminogen activator
timeFrame: 5 days
measure: Postoperative non-surgical complications
timeFrame: 30 days
Secondary outcomes:
measure: CD2 Cellular immunologic parameter (non-radioisotope),
timeFrame: 5 days
measure: CD3 Cellular immunologic parameter (non-radioisotope),
timeFrame: 5 days
measure: CD4 Cellular immunologic parameter (non-radioisotope),
timeFrame: 5 days
measure: CD 8 Cellular immunologic parameter (non-radioisotope),
timeFrame: 5 days
measure: CD 8 Cellular immunologic parameter (non-radioisotope),
timeFrame: 5 days
measure: CD 25 Cellular immunologic parameter (non-radioisotope),
timeFrame: 5 days
measure: CD 30 Cellular immunologic parameter (non-radioisotope),
timeFrame: 5 days
measure: CD 19 Cellular immunologic parameter (non-radioisotope),
timeFrame: 5 days
measure: CD 20 Cellular immunologic parameter (non-radioisotope),
timeFrame: 5 days
measure: CD 138 Cellular immunologic parameter (non-radioisotope),
timeFrame: 5 days
measure: CD 56 Cellular immunologic parameter (non-radioisotope),
timeFrame: 5 days
measure: CD 303 Cellular immunologic parameter (non-radioisotope),
timeFrame: 5 days
measure: CLT cytotoxicity (non-radioisotope),
timeFrame: 5 days
measure: CD 304
timeFrame: 5 days
measure: NK cytotoxicity
timeFrame: 5 days
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Faculty of Medicine Siriraj Hospital, Mahidol University
Study officials:
affiliation: Mahidol University
name: Sirilak Suksompong, MD
role: STUDY_DIRECTOR
References:
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.
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. doi: 10.1055/s-2000-323. German.
citation: 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.
citation: 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.
citation: 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.
citation: 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.