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Project title Description Available from (date) Contact

Red cell storage duration and procoagulant effects: Role of microparticles and smaller particles

The routine storage of packed red blood cells (PRBCs) at 2-6°C for up to 42 days results in time-dependent degradation in red blood cell (RBC) morphology, metabolism and function, and is a potential risk factor for increased thrombosis in transfused patients. The exact mechanism remains unknown; however, small particles that are released from red blood cells during storage have been implicated via the expression of procoagulant phosphololipids on their surfaces. These small particles may also act as carriers for microRNAs, small non-coding RNAs that modulate protein translation, including potentially for proteins involved in coagulation. These small particles include microparticles (MPs; typically 100 - 1,000 nm in size) as well as nanoparticles (typically 60 - 80 nm in size), and their generation depends on the specific blood collection and manufacturing procedures in use. We have previously demonstrated accumulation of microparticlaes in stored red blood cells; however, we found that removal of particles larger than 220nm in size did not prevent PBRC-induced coagulation in a laboratory assay. This project will therefore confirm this finding using an alternative coagulation assay (thrombin generation assay). It will also characterise the smaller particles (i.e. smaller than 220nm) and how removal of different sizes of these smaller particles (i.e. 75 - 100 nm or 100 - 200nm) impacts coagulation assays. It will also generate artificial small particles of a range of sizes (i.e. 15 - 50nm, 100 - 200nm and 1,000nm) and determine the procoagulant potential of these artificial small particles. Finally, it will determine the microRNA profile of PRBC units and investigate the potential contribution of these microRNAs to PRBC-mediated coagulation.

1/7/17

Dr John-Paul Tung