Investigating the biophysical cues associated with platelet deterioration over storage

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Platelet (PLT) transfusions are essential in mitigating the bleeding risk of patients with active bleeding or thrombocytopenia. However, PLTs undergo a series of deleterious changes from the point of blood withdrawal to the time of transfusion, known as the PLT storage lesion (PSL). With the Welsh Blood Service supplying ~15,000–20,000 PLT concentrates (PCs) annually in Wales, and with 10 - 20% of PCs expiring before use, optimising storage of PCs is critical to meet the growing demand for reliable transfusion products while reducing waste and the associated cost burden to the NHS. Based on research conducted up to the 1980s, PC storage guidelines suggest limiting storage to 5-7 days in gas permeable bags at 22°C +/- 2°C under constant agitation to ensure PC quality. While recent research into the PSL has mainly focused on the effects of reduced temperature storage, the impact of the biophysical environment on the PSL has been comparatively overlooked. This thesis investigated the impact of agitation on PC storage with respect to oxygen (O₂) transfer, fluid dynamics, and the rheological properties of the suspension, and how these factors affect in vitro PC quality. Computational fluid dynamics (CFD), bead tracking analysis, co-stream microfluidics, and nanoparticle tracking microrheometry were used to characterise the biophysical storage environment, while O₂ availability was assessed via CFD, electron paramagnetic resonance oximetry, and Fickian diffusion modelling. PLT quality was measured using multiple electrode aggregometry, flow cytometry, biochemical, and haematology analyses. Results showed that agitation significantly influenced shear stress but not O₂ availability, which was primarily limited by storage bag permeability; though, O₂ levels remained sufficient for both adult and neonatal PCs. Shear stress was higher in small-volume PCs, where reducing agitation to 40 rpm improved quality throughout storage and 20 rpm improved early storage outcomes compared with 60 rpm. Plasma content was the main contributor to viscosity, but ≥10% plasma was required to preserve morphology, function, and viability. Thus, reduced plasma approaches are not a viable option for mitigating the shear induced PSL. This thesis proposes a novel mechanism by which agitation influences PC storage quality, primarily by maintaining PLT suspension rather than enhancing oxygenation. Reduced agitation emerged as a promising strategy to improve storage outcomes for PCs reserved for neonatal transfusion. An alternative approach to reduce shear stress includes delaying the splitting of PCs until transfusion is requested for neonatal use.

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