Blood-CRE: Centre of Research Excellence for Patient Blood Management in Critical Illness and Trauma

Blood-CRE visual icon

The Blood-CRE brought together a world-class team of investigators with the support of the key clinical specialties and blood sector stakeholders. It evaluated current transfusion practice and led an innovative program of research that tested novel approaches to blood management. The Blood-CRE was a catalyst to translation of findings to drive policy and practice; increased blood transfusion research capacity; enhanced and expanded collaboration; and improved patient outcomes.

Transfusion of blood products is one of the most common medical procedures in hospital patients. Despite common usage, there has been considerable uncertainty about the relative risks and benefits of transfusions with a large and growing body of literature that questioned the appropriateness of many common transfusion practices in terms of patient outcomes. Some guidelines for patient blood management were based on inadequate evidence, and compliance with their recommendations was reputedly poor.Photo of Jamie Cooper

In 2012, Monash University received $2.5 million in National Health and Medical Research Council (NHMRC) funding to establish the Centre of Research Excellence for Patient Blood Management in Critical Illness and Trauma at Monash University-the Blood-CRE. The Blood-CRE, was led by Intensive Care physician Professor Jamie Cooper of the University's Department of Epidemiology and Preventive Medicine (DEPM) and represented a consortia of national research and key organisations responsible for the regulation, manufacture, supply and surveillance of blood products including the Australian Red Cross Blood Service, National Blood Authority, Transfusion Outcomes Research Collaborative (TORC), Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), Australian Defence Force, Australian and New Zealand Society for Blood Transfusion, and the Australian and New Zealand Intensive Care Society Centre for Outcomes and Resource Evaluation (ANZICS-CORE).

The Blood-CRE coordinated a research strategy that evaluated current clinical practice through existing and extended clinical registries, conducted preliminary observational research and large multicentre randomised controlled trials (RCTs), and evaluated the translation of evidence into policy and practice. The Blood-CRE research strategy diagram (pictured below) describes the key research foci and their interactions within the Centre: clinical registries; prospective clinical research; and practice, policy and stewardship.Blood-CRE research strategy

The key facets of the Blood-CRE were:

1. Understanding current transfusion practice informed through expansion of the Australasian Massive Transfusion Registry to all major acute care hospitals. Valuable information was also be generated by expanding the TORC Data Linkage program to include linkage to the ANZICS-CORE database, Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) cardiac surgery database, trauma registries throughout the country, and the National Death Index (NDI). This expansion took advantage of the DEPM's long and successful history of registry development.

2. Optimising stewardship of donor blood and cost effectiveness of transfusion by studying the effects of duration and methods of blood storage in critical illness and trauma, and by conducting cost-effectiveness analyses. The TRANSFUSE-RCT tested the hypothesis that, for critically ill patients who require transfusion, administration of freshest available red blood cells (RBCs), compared with standard inventory management, would improve survival. The hypothesis was not proven saving blood services from around the world the additional costs and logistical issues associated with decreasing the “use by” date of fresh blood units. Blood component storage methodology was also examined by University of Queensland researchers and the Australian Defence Force in a pilot trial of the administration of frozen platelets in bleeding cardiac surgery patients. This pilot trial led to a NHMRC phase III trial using frozen platelets, currently underway.

3. Minimising transfusion requirements in critical illness and trauma was examined in a Western Australian government funded pilot trial studying the impact of the administration of IV iron in critically ill patients on blood transfusion requirements and clinical outcomes. Ongoing research continues in a NHMRC-funded randomised controlled trial comparing pre-hospital administration of tranexamic acid to standard management in bleeding trauma patients, with trial completion expected in late 2021.

The Blood-CRE has been associated with numerous presentations at national and international conferences and >50 publications including in high impact journals such as the New England Journal of Medicine. It developed greater research capacity in the fields of transfusion by providing a scholarship to post graduate students and supporting courses in research methodology for early career researchers run in Queensland, New South Wales and at the Monash University campus in Italy. The Blood-CRE also facilitated increased international collaborations resulting in a USA/Australian NIH funded meta-analysis research project. All of which maximises our ability to effect change in transfusion practice and improve patient outcomes.

Publications

Publications related to the Blood-CRE include:

Reade MC, Marks DC, Bellomo R, Deans R, Faulke DJ, Fraser JF, Gattas DJ, Holley AD, Irving DO, Johnson L, Pearse BL, Royse AG, Wong J; Cryopreserved vs Liquid Platelet (CLIP) Investigators, the Australian and New Zealand College of Anaesthetists Clinical Trials Network, and the Australian and New Zealand Intensive Care Society Clinical Trials Group. A randomized, controlled pilot clinical trial of cryopreserved platelets for perioperative surgical bleeding: the CLIP-I trial (Editorial, p. 2759). Transfusion 2019;59:2794-2804.  PMID: 31290573.

Aubron C, McQuilten Z, Bailey M, Board J, Buhr H, Cartwright B, Dennis M, Hodgson C, Forrest P, McIlroy D, Murphy D, Murray L, Pellegrino V, Pilcher D, Sheldrake J, Tran H, Vallance S, Cooper DJ; endorsed by the International ECMO Network (ECMONet). Low-Dose Versus Therapeutic Anticoagulation in Patients on Extracorporeal Membrane Oxygenation: A Pilot Randomized Trial. Crit Care Med 2019;47:e563-e571. PMID: 31033512.

Irving A, Higgins A, Ady B, Bellomo R, Cooper DJ, French C, Gantner D, Harris A, Irving DO, Murray L, Nichol A, Petrie D, McQuilten ZK; Standard Issue Transfusion versus Fresher Red-Cell Use in Intensive Care (TRANSFUSE) Investigators and Australian and New Zealand Intensive Care Society Clinical Trials Group. Fresh Red Cells for Transfusion in Critically Ill Adults: An Economic Evaluation of the Standard Issue Transfusion Versus Fresher Red-Cell Use in Intensive Care (TRANSFUSE) Clinical Trial. Crit Care Med 2019;47:e572-e579. PMID: 31008734.

Burns KE, Haysom HE, Higgins AM, Waters N, Tahiri R, Rushford K, Dunstan T, Saxby K, Kaplan Z, Chunilal S, McQuilten ZK, Wood EM. A time-driven, activity-based costing methodology for determining the costs of red blood cell transfusion in patients with beta thalassaemia major. Transfus Med 2019;29:33-40. PMID: 29637650.

Aubron C, Kandane-Rathnayake RK, Andrianopoulos N, Westbrook A, Engelbrecht S, Ozolins I, Bailey M, Murray L, Cooper DJ, Wood EM, McQuilten ZK; Blood Observational Study investigators; ANZICS Clinical Trials Group. Day or overnight transfusion in critically ill patients: does it matter? Vox Sang 2018;113:275-282. PMID: 29392786.

Cooper DJ, McQuilten ZK, Nichol A, Ady B, Aubron C, Bailey M, Bellomo R, Gantner D, Irving DO, Kaukonen KM, McArthur C, Murray L, Pettilä V, French C; TRANSFUSE Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Age of Red Cells for Transfusion and Outcomes in Critically Ill Adults. N Engl J Med 2017;377:1858-1867. PMID: 28952891.

McQuilten ZK, Wood EM, Bailey M, Cameron PA, Cooper DJ. Fibrinogen is an independent predictor of mortality in major trauma patients: A five-year statewide cohort study. Injury 2017;48:1074-1081.  PMID: 28190583.

Ruseckaite R, McQuilten ZK, Oldroyd JC, Richter TH, Cameron PA, Isbister JP, Wood EM. Descriptive characteristics and in-hospital mortality of critically bleeding patients requiring massive transfusion: results from the Australian and New Zealand Massive Transfusion Registry. Vox Sang 2017;112:240-248. PMID: 28181262.

Aubron C, DePuydt J, Belon F, Bailey M, Schmidt M, Sheldrake J, Murphy D, Scheinkestel C, Cooper DJ, Capellier G, Pellegrino V, Pilcher D, McQuilten Z. Predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation. Ann Intensive Care 2016;6:97. PMID: 27714705.

Oldroyd JC, Venardos KM, Aoki NJ, Zatta AJ, McQuilten ZK, Phillips LE, Andrianopoulos N, Cooper DJ, Cameron PA, Isbister JP, Wood EM. Improving outcomes for hospital patients with critical bleeding requiring massive transfusion: the Australian and New Zealand Massive Transfusion Registry study methodology. BMC Res Notes 2016;9:457. PMID: 27716381.

McQuilten ZK, Crighton G, Engelbrecht S, Gotmaker R, Brunskill SJ, Murphy MF, Wood EM. Transfusion interventions in critical bleeding requiring massive transfusion: a systematic review. Transfus Med Rev 2015;29:127-37. PMID: 25716645.

McQuilten ZK, Andrianopoulos N, van de Watering L, Aubron C, Phillips L, Bellomo R, Pilcher D, Cameron P, Reid CM, Cole-Sinclair MF, Newcomb A, Smith J, McNeil JJ, Wood EM. Introduction of universal prestorage leukodepletion of blood components, and outcomes in transfused cardiac surgery patients. J Thorac Cardiovasc Surg. 2015;150:216-22. PMID: 25940409.

McQuilten ZK, Andrianopoulos N, Wood EM, Cole-Sinclair MF, McNeil JJ, Cameron PA, Reid CM, Newcomb AE, Smith JA, Phillips LE. Transfusion practice varies widely in cardiac surgery: Results from a national registry. J Thorac Cardiovasc Surg 2014;147:1684-1690.e1. PMID: 24332109.

Kaukonen KM, Bailey M, Ady B, Aubron C, French C, Gantner D, Irving D, Murray L, Nichol A, Pettilä V, McQuilten Z, Cooper DJ. A randomised controlled trial of standard transfusion versus fresher red blood cell use in intensive care (TRANSFUSE): protocol and statistical analysis plan. Crit Care Resusc 2014;16:255-61. PMID: 25437218.

Milford EM, Reade MC, Shekar K, Tung JP, Fraser JF. An age-of-blood transfusion trial in the trauma setting is crucial and animal models may help inform trial design. Crit Care Resusc 2014;16:149-50. PMID: 24888291.

Gruen RL, Jacobs IG, Reade MC. Tranexamic acid and trauma. Med J Aust 2014;200:255. PMID: 24641138.

Aubron C, Kaukonen KM, McQuilten Z, Cameron P, Bailey M, Cooper DJ. Is an age-of-blood transfusion trial in trauma patients in Australia and New Zealand feasible? Crit Care Resusc 2013;15:159-61. PMID: 23944200.

Litton E, Xiao J, Ho KM. Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials. BMJ. 2013;347:f4822. PMID: 23950195.

For further information: please contact Lynne Murray by email.