Proceedings of the Food and Drug Administration public workshop on pathogen reduction technologies for blood safety 2018 (Commentary, p. 3026)

Atreya, Chintamani; Glynn, Simone; Busch, Michael; Kleinman, Steve; Snyder, Edward; Rutter, Sara; AuBuchon, James; Flegel, Willy; Reeve, David; Devine, Dana; Cohn, Claudia; Custer, Brian; Goodrich, Raymond; Benjamin, Richard J.; Razatos, Anna; Cancelas, Jose; Wagner, Stephen; Maclean, Michelle; Gelderman, Monique; Cap, Andrew; Ness, Paul

In addition to investing in technologies that use various photosensitizers and UV light to damage nucleic acids in pathogens and WBCs, the DOD has pursued alternative blood storage approaches to not only reduce infectious risks of transfusion but also increase the availability of PLTs, since current room temperature storage practices limit shelf life to 5 to 7 days. Refrigeration has been demonstrated to significantly reduce bacterial growth as well as reduce the metabolic activity of PLTs during storage, preserving their hemostatic function. Refrigerated PLTs retain significant capacity to adhere to collagen under shear, aggregate, release granules, catalyze thrombin generation, and contract clots for up to 21 days. 179 Refrigeration causes partial activation of PLTs, leading to desialylation of membrane proteins and clearance from circulation over 1-2 days in vivo. 180 Nevertheless, in a randomized trial in cardiac surgery patients, refrigerated PLTs stored for up to 14 days performed comparably to standard-of-care PLTs stored for less than 7days (K.M. Reddoch Cardenas and A. Cap, unpublished, 2019) . 181 PLTs can be refrigerated in either plasma or PAS, and preliminary results suggest that PRT-treated PLTs can also be refrigerated without loss of hemostatic function. 182, 183 Refrigeration thus offers not only an extra layer of protection from bacterial pathogens in addition to PRT, but also an opportunity to extend shelf life and availability while preserving the essential contribution of PLTs to bleeding control. It should be noted that refrigerated WB contains active PLTs that have been shown to maintain considerable hemostatic function through the entire shelf life of WB (up to 35 days in CPDA-1). 184, 185 The DOD is also supporting the development of other alternative storage modalities for PLTs such as cryopreservation and lyophilization. 178, 186 Both technologies offer extended storage times (years) and bacterial pathogen risk reduction and could be combined with PRT. While the clinical safety and efficacy of these products is being established, refrigeration with or without PRT offers a practical way to improve PLT product safety and availability. WB PRT remains an important capability gap for the US military, but a technology using riboflavin and UV light has been shown to yield a product with preserved hemostatic function and to inactivate Ebola virus, among other pathogens, and reduce transfusion-transmitted malaria; this technology is in Phase III trials. 123, 184, 187 Successful development of WB PRT will be a landmark achievement in the history of transfusion medicine and will benefit both civilian and military patients.