BLOOD MANAGEMENT Impact of cold storage on platelets treated with Intercept pathogen inactivation Katrijn R. Six , 1,2 Rosalie Devloo, 1 Veerle Compernolle, 1,2,3 and Hendrik B. Feys 1,2 BACKGROUND: Pathogen inactivation and cold or cryopreservation of platelets (PLTs) both significantly affect PLT function. It is not known how PLTs function when both are combined. STUDY DESIGN AND METHODS: Standard PLT concentrates (PCs) were compared to pathogen- inactivated PCs treated with amotosalen photochemical treatment (AS-PCT) when stored at room (RT, 22  C), cold (4  C, n = 6), or cryopreservation (-80  C, n = 8) temperatures. The impact of alternative storage methods on both arms was studied in flow cytometry, light transmittance aggregometry, and hemostasis in collagen-coated microfluidic flow chambers. RESULTS: Platelet aggregation of cold-stored AS-PCT PLTs was 44%  11% compared to 57%  14% for cold- stored standard PLTs and 58%  21% for RT-stored AS- PCT PLTs. Integrin activation of cold-stored AS-PCT PLTs was 53%  9% compared to 77%  6% for cold-stored standard PLTs and 69%  13% for RT-stored AS-PCT PLTs. Coagulation of cold-stored AS-PCT PLTs started faster under flow (836  140 sec) compared to cold-stored standard PLTs (960  192 sec) and RT-stored AS-PCT PLTs (1134  220 sec). Fibrin formation rate under flow was also highest for cold-stored AS-PCT PLTs. This was in line with thrombin generation in static conditions because cold-stored AS-PCT PLTs generated 297  47 nmol/L thrombin compared to 159  33 nmol/L for cold-stored standard PLTs and 83  25 nmol/L for RT- stored AS-PCT PLTs. So despite decreased PLT activation and aggregation, cold storage of AS-PCT PLTs promoted coagulation. PLT aggregation of cryopreserved AS-PCT PLTs (23%  10%) was not significantly different from cryopreserved standard PLTs (25%  8%). CONCLUSION: This study shows that cold storage of AS-PCT PLTs further affects PLT activation and aggregation but promotes (pro)coagulation. Increased procoagulation was not observed after cryopreservation. C onventional, room temperature (RT) storage of platelets (PLTs) limits shelf life to between 4 and 7 days because of the risk of bacterial contamina- tion and the decrease in PLT function called platelet storage lesion. 1 The limited shelf life of PLT concen- trates (PCs) hampers efficient inventory management and puts pressure on blood banks trying to balance risks of short- age with risks of wastage. Prolonging PC shelf life could over- come this problem and has been investigated for decades with a focus on cold storage (1-6  C) 2 and cryopreservation (-80 to -196  C). 3,4 Cold storage can potentially increase PC shelf life beyond 7 days of storage. 5 Several reports indicate that cold-stored PLTs are functionally “primed” suggesting that these are in a state of heightened responsiveness to hemostatic stimuli. 5–7 The main obstacle for cold-stored PLTs is the significantly faster clearance from circulation compared to RT storage. 2,8,9 This may be less relevant in acutely bleeding patients who ABBREVIATIONS: AS-PCT = amotosalen photochemical treatment; ETP = endogenous thrombin potential; MP = microparticle; PC(s) = platelet concentrate(s); PS = phosphatidylserine; RT = room temperature; TF = tissue factor. From the 1 Transfusion Research Center, Belgian Red Cross-Flanders, the 2 Faculty of Medicine and Health Sciences, Ghent University, Ghent, and the 3 Blood Service of the Belgian Red Cross-Flanders, Mechelen, Belgium. Address reprint requests to: Hendrik B. Feys, Transfusion Research Center, Belgian Red Cross Flanders, Ottergemsesteenweg 413, Ghent, 9000, Belgium; e-mail: hendrik.feys@rodekruis.be. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. This research was supported by the Foundation for Scientific Research of the Belgian Red Cross Flanders. KRS is a fellow of the Special Research Fund of Bijzonder Onderzoeksfonds (BOFDOC2016000401). Received for publication December 12, 2018; revision received May 23, 2019, and accepted May 23, 2019. doi:10.1111/trf.15398 © 2019 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB. TRANSFUSION 2019;00;1–10 TRANSFUSION 1