Project title

First Large Animal (Ovine) Model of Transfusion-Related Acute Lung Injury

Researchers

John-Paul Tung, Gabi Simonova, Sara Diab, Kimble Dunster, Saul Chemonges, Adrian Barnett,
Maria Naatamadja, John Fraser, Lin Fung


Background


CCRG, in collaboration with the Australian Red Cross Blood Service, has developed the first large animal model of TRALI in sheep. Over recent years, TRALI has been the most frequent cause of transfusion-related morbidity and mortality. Patients with TRALI develop difficulty in breathing either during or soon after receiving a blood transfusion, and may require supplemental oxygen or even mechanical ventilation. Even so, 5 – 40% of patients who develop TRALI go on to die. TRALI is hypothesised to develop via a two-event mechanism in which the patient’s underlying condition interacts with factors within the transfused blood product to induce injury. Patients receive blood transfusions for various reasons, making it difficult to define exactly how their underlying condition may contribute to the development of TRALI. The causative factors within the blood products are either antibodies against white blood cells or proteins and lipids that accumulate in blood products during routine storage. Despite a multitude of research, the precise mechanisms by which TRALI develops remains uncertain. Animal models, such as that developed by our group, will be crucial in resolving this uncertainty because both the patient and blood product factors that may contribute to the development of TRALI can be precisely controlled.

In our model, we have demonstrated that in “sick” sheep that received lipopolysaccharide as a model of a bacterial infection, transfusion of the soluble fraction of stored rather than fresh packed red blood cell (PRBC) or platelet units induced TRALI. Additionally, PRBC-induced TRALI was associated with more severe haemodynamic changes than platelet- induced TRALI.

This work has received national and international recognition with several presentations and publications resultant. Additionally, in 2009, an abstract from this study was awarded the Australian and New Zealand Society of Blood Transfusion Presidential Prize, and this year a paper from this study was awarded the Vox Sanguinis Best Paper Prize, for the best paper in this journal during 2011 and the Graeme Nielsen Best Paper Prize for the best research paper published by TPCH.

The ovine TRALI model is currently being used to investigate the role of white blood cell antibodies as a trigger for TRALI as well as whether pre-storage leucoreduction of blood products reduces the accumulation of proteins and lipids during storage, which in turn reduces the risk of TRALI. We are also characterising the protein and lipid factors that may be responsible for the development of TRALI.


Publications


Fraser, JF., Spooner, AJ., Dunster, KR., Anstey, CM, Corley, A. Nasal high flow oxygen therapy in COPD patients reduces respiratory rate and tissue carbon dioxide whilst increasing tidal and end-expiratory lung volumes: a randomised crossover trial. Accepted by Thorax journal.