GENetic profiling: Outcome, Mechanism and Immunity, compare intraoperative Cell Salvage and allogeneic blood transfusion - the GEN-MICS study

GENetic profiling: Outcome, Mechanism and Immunity, compare intraoperative Cell Salvage and allogeneic blood transfusion - the GEN-MICS study

 

CIA: Dr Michelle Roets

Autologous blood transfusion may be a solution to improving immune competence and reducing infectious complications following transfusion, during orthopaedic surgery and translatable to many other surgical sub-specialties.

Project summary

Many advances in surgery have been underpinned by the ability to remedy blood loss. Allogeneic (donated) blood transfusion (ABT) is often essential and lifesaving during major trauma and surgery. Intraoperative cell salvage (ICS) is increasingly accepted as a safe alternative to ABT and permits a patient’s own blood (autologous blood), lost during surgery to be collected, processed and reinfused. The safety of ABT has improved over centuries however significant risks remain.

Transfusion related immune modulation (TRIM) describes delayed modulation of immune responses and subsequent adverse outcomes following ABT. Even though the precise mechanism of action is still unclear, TRIM can be reduced by using ICS instead. Related adverse outcomes, confirmed through clinical outcome and in vitro studies, include an increased risk of cancer recurrence and postoperative bacterial infection. When challenged by infection the human immune system responds through the activation of immune cells, subsequent chemotaxis and signalling to resist the insult. Mediators (for example cytokines, chemokines and immune cell surface markers) are produced following activation of specific immune pathways. This activation is driven by changes at the genetic level. Cells use genetic codes such as messenger RNA (mRNA) to direct specific cellular responses. In this way the “transcriptome” can be used to understand cell function. Characterising changes in the cell transcriptome would provide valuable insights into changes in the genetic immune profile that occur during surgery, ABT and ICS.

The world first TRIMICS study, funded by ANZCA and National Blood Authority grants, provided evidence of improved immune competence and a reduction of immune modulation in monocyte and dendritic cell function when ICS was used instead of ABT.  This follow up GEN-MICS study will use RNA (from the same patient cohort), stored during the TRIMICS study. RNA sequencing will be used to assess changes in the transcriptome and specific pathways modified following exposure to ICS and/or ABT mapped. 

The team will investigate specific changes in key pathways driving the immune response (associated with transfusion) and facilitate discovery of potential biomarkers of immune modulation leading to poor patient outcomes (such as infection).
The relevant cost and morbidity associated with transfusion are important concerns for hospitals and patients across Australia and worldwide. ABT is an important independent statistical predictor of postoperative infection and associated with a 29 per cent increased risk for major infection after surgery. Autologous blood transfusion may be a solution to improving immune competence and reducing infectious complications following transfusion, during orthopaedic surgery and translatable to many other surgical sub-specialties.

Chief investigators

Dr Michelle Roets, Associate Professor Kerstin Wyssusek, Professor Andre van Zundert, Royal Brisbane and Women’s Hospital, Queensland, Associate Professor Melinda Dean, University of the Sunshine Coast, Queensland,  Associate Professor David Sturgess, Surgical Treatment and Rehabilitation Service Hospital, Queensland, Professor Robert Flower, Australian Red Cross Blood Service, Queensland,  Dr John-Paul Tung, Dr Alexis Perros, Australian Red Cross Lifeblood, Queensland.
 

Funding

The project was awarded $A66,500 (including scholarship) through the ANZCA research grants program for 2022.   

Last updated 14:36 8.03.2022