Examining the non-haemostatic function of alternatively stored platelets

Winskel-Wood, Ben

Examining the non-haemostatic function of alternatively stored platelets

Winskel-Wood, Ben

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Publication Type:: Thesis
Issue Date:: 2023

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Field	Value	Language
dc.contributor.author	Winskel-Wood, Ben
dc.date.accessioned	2023-10-17T02:48:10Z
dc.date.available	2023-10-17T02:48:10Z
dc.date.issued	2023
dc.identifier.uri	http://hdl.handle.net/10453/172721
dc.description	University of Technology Sydney. Faculty of Science.	en_US.UTF-8
dc.description.abstract	Currently, platelet components are stored at room-temperature, limiting the shelf life to 5-7 days due to the risk of bacterial proliferation and a gradual reduction in haemostatic function. The short shelf-life makes maintaining platelet supplies to remote medical centres impractical. Further, between 10 20% of platelet products are discarded due to expiry. Consequently, there has been renewed interest in the evaluation of alternative storage methodologies including platelet refrigeration and platelet cryopreservation. Both techniques allow for the potential extension of shelf-life while better preserving the haemostatic function of platelets compared to room temperature storage. Recent findings have identified that both refrigeration and cryopreservation alter the abundance of receptors on the surface membrane and soluble factors released into the supernatant. Additionally, storage induced changes in immune phenotype have been linked to adverse events post-transfusion in room-temperature stored components. In general, very little is known about the effects of refrigeration and cryopreservation on the immune characteristics of platelets. As such, the overall aim of this thesis was to address these knowledge gaps to further aid the clinical evaluation of refrigerated and cryopreserved platelets. Receptors on the platelet surface membrane facilitate pathogen recognition, leukocyte interaction and leukocyte activation. Platelet activation can mobilise receptors from internal stores to the surface membrane. This can influence the ability of platelets to adhere to pathogens and leukocytes. Platelet-pathogen recognition is linked to direct pathogen killing, clearance and also immune evasion. In contrast, platelet-leukocyte interaction can lead to the formation of platelet-leukocyte aggregates which mediate anti-pathogenic activity, platelet clearance, leukocyte differentiation and pro-inflammatory function. In this dissertation, the effect of refrigeration and cryopreservation on the abundance of immune receptors on the platelet surface membrane was examined. This information provides insight into how alternatively stored platelets may interact with pathogens and other immune cells. Platelet activation induced by storage or immunological stimuli can cause degranulation, releasing a range of soluble factors into the surroundings, facilitating pathogen clearance, cellular proliferation, leukocyte migration and inflammation. Notably, the accumulation of pro-inflammatory soluble factors in the supernatant of platelet components has been directly linked with an increased risk of adverse events post-transfusion. The research presented in this thesis characterises the concentration of pro-inflammatory mediators in the platelet supernatant which may provide insight into the likelihood of adverse transfusion events. Consequently, this dissertation aims provide a greater understanding of how alternative platelet storage methodologies affect the immune characteristics and function of platelets in vitro.	en_US.UTF-8
dc.format	Thesis (PhD)
dc.language.iso	en_US	en_US.UTF-8
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/172721/1/thesis.pdf
dc.rights	info:eu-repo/semantics/openAccess
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	© 2023 Ben Winskel-Wood
dc.rights	au.edu.uts.lib/cph
dc.title	Examining the non-haemostatic function of alternatively stored platelets	en_US.UTF-8
dc.type	Thesis
utslib.copyright.status	open_access	*

Abstract:

Currently, platelet components are stored at room-temperature, limiting the shelf life to 5-7 days due to the risk of bacterial proliferation and a gradual reduction in haemostatic function. The short shelf-life makes maintaining platelet supplies to remote medical centres impractical. Further, between 10 20% of platelet products are discarded due to expiry. Consequently, there has been renewed interest in the evaluation of alternative storage methodologies including platelet refrigeration and platelet cryopreservation. Both techniques allow for the potential extension of shelf-life while better preserving the haemostatic function of platelets compared to room temperature storage. Recent findings have identified that both refrigeration and cryopreservation alter the abundance of receptors on the surface membrane and soluble factors released into the supernatant. Additionally, storage induced changes in immune phenotype have been linked to adverse events post-transfusion in room-temperature stored components. In general, very little is known about the effects of refrigeration and cryopreservation on the immune characteristics of platelets. As such, the overall aim of this thesis was to address these knowledge gaps to further aid the clinical evaluation of refrigerated and cryopreserved platelets. Receptors on the platelet surface membrane facilitate pathogen recognition, leukocyte interaction and leukocyte activation. Platelet activation can mobilise receptors from internal stores to the surface membrane. This can influence the ability of platelets to adhere to pathogens and leukocytes. Platelet-pathogen recognition is linked to direct pathogen killing, clearance and also immune evasion. In contrast, platelet-leukocyte interaction can lead to the formation of platelet-leukocyte aggregates which mediate anti-pathogenic activity, platelet clearance, leukocyte differentiation and pro-inflammatory function. In this dissertation, the effect of refrigeration and cryopreservation on the abundance of immune receptors on the platelet surface membrane was examined. This information provides insight into how alternatively stored platelets may interact with pathogens and other immune cells. Platelet activation induced by storage or immunological stimuli can cause degranulation, releasing a range of soluble factors into the surroundings, facilitating pathogen clearance, cellular proliferation, leukocyte migration and inflammation. Notably, the accumulation of pro-inflammatory soluble factors in the supernatant of platelet components has been directly linked with an increased risk of adverse events post-transfusion. The research presented in this thesis characterises the concentration of pro-inflammatory mediators in the platelet supernatant which may provide insight into the likelihood of adverse transfusion events. Consequently, this dissertation aims provide a greater understanding of how alternative platelet storage methodologies affect the immune characteristics and function of platelets in vitro.

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http://hdl.handle.net/10453/172721