Review
The long and winding road to pathogen reduction of platelets, red blood cells and whole blood
Paolo Rebulla,
Corresponding Author
Paolo Rebulla
Department of Transfusion Medicine and Haematology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Correspondence: Paolo Rebulla, MD, Department of Transfusion Medicine and Haematology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
E-mail: [email protected]
Search for more papers by this authorPaolo Rebulla,
Corresponding Author
Paolo Rebulla
Department of Transfusion Medicine and Haematology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Correspondence: Paolo Rebulla, MD, Department of Transfusion Medicine and Haematology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
E-mail: [email protected]
Search for more papers by this authorSummary
Pathogen reduction technologies (PRTs) have been developed to further reduce the current very low risks of acquiring transfusion-transmitted infections and promptly respond to emerging infectious threats. An entire portfolio of PRTs suitable for all blood components is not available, but the field is steadily progressing. While PRTs for plasma have been used for many years, PRTs for platelets, red blood cells (RBC) and whole blood (WB) were developed more slowly, due to difficulties in preserving cell functions during storage. Two commercial platelet PRTs use ultra violet (UV) A and UVB light in the presence of amotosalen or riboflavin to inactivate pathogens’ nucleic acids, while a third experimental PRT uses UVC light only. Two PRTs for WB and RBC have been tested in experimental clinical trials with storage limited to 21 or 35 days, due to unacceptably high RBC storage lesion beyond these time limits. This review summarizes pre-clinical investigations and selected outcomes from clinical trials using the above PRTs. Further studies are warranted to decrease cell storage lesions after PRT treatment and to test PRTs in different medical and surgical conditions. Affordability remains a major administrative obstacle to PRT use, particularly so in geographical regions with higher risks of transfusion-transmissible infections.
Disclosure of conflicts of interests
The author has previously received institutional research grants from Cerus and Terumo BCT to support the IPTAS clinical trial, and honoraria and travel expenses from Terumo BCT. The author has previously been a member of the scientific advisory board of Macopharma.
References
- Abonnenc, M., Sonego, G., Kaiser-Guignard, J., Crettaz, D., Prudent, M., Tissot, J.D. & Lion, N. (2015) In vitro evaluation of pathogen-inactivated buffy coat-derived platelet concentrates during storage: psoralen-based photochemical treatment step-by-step. Blood Transfusion, 13, 255–264.
- van Aelst, B., Devloo, R., Vandekerckhove, P., Compernolle, V. & Feys, H.B. (2015) Ultraviolet C light pathogen inactivation treatment of platelet concentrates preserves integrin activation but affects thrombus formation kinetics on collagen in vitro. Transfusion, 55, 2404–2014.
- van Rhenen, D.J., Vermeij, J., Mayaudon, V., Hind, C., Lin, L. & Corash, L. (2000) Functional characteristics of S-59 photochemically treated platelet concentrates derived from buffy coats. Vox Sanguinis, 79, 206–214.
- van Rhenen, D., Gulliksson, H., Cazenave, J.P., Pamphilon, D., Ljungman, P., Klüter, H., Vermeij, H., Kappers-Klunne, M., de Greef, G., Laforet, M., Lioure, B., Davis, K., Marblie, S., Mayaudon, V., Flament, J., Conlan, M., Lin, L., Metzel, P., Buchholz, D. & Corash, L. (2003) Transfusion of pooled buffy coat platelet components prepared with photochemical pathogen inactivation treatment: the euroSPRITE trial. Blood, 101, 2426–2433.
- Agapova, M., Lachert, E., Brojer, E., Letowska, M., Grabarczyk, P. & Custer, B. (2015) Introducing pathogen reduction technology in Poland: a cost-utility snalysis. Transfusion Medicine and Hemotherapy, 42, 158–165.
- Ainley, L.I. & Hewitt, P.E. (2018) Haematology patients and the risk of transfusion transmitted infection. British Journal of Haematology, 180, 473–483.
- Allain, J.P., Stramer, S.L., Carneiro-Proietti, A.B., Martins, M.L., Lopes da Silva, S.N., Ribeiro, M., Proietti, F.A. & Reesink, H.W. (2009) Transfusion-transmitted infectious diseases. Biologicals, 37, 71–77.
- Allain, J.P., Owusu-Ofori, A.K., Assennato, S.M., Marschner, S., Goodrich, R.P. & Owusu-Ofori, S. (2016) Effect of Plasmodium inactivation in whole blood on the incidence of blood transfusion-transmitted malaria in endemic regions: the African Investigation of the Mirasol System (AIMS) randomised controlled trial. Lancet, 387, 1753–1761.
- Apelseth, T.O., Bruserud, O., Wentzel-Larsen, T., Bakken, A.M., Bjørsvik, S. & Hervig, T. (2007) In vitro evaluation of metabolic changes and residual platelet responsiveness in photochemical treated and gamma irradiated single-donor platelet concentrates during long-term storage. Transfusion, 47, 653–665.
- Arbaeen, A.F., Schubert, P., Serrano, K., Carter, C.J., Culibrk, B. & Devine, D.V. (2017) Pathogen inactivation treatment of plasma and platelet concentrates and their predicted functionality in massive transfusion protocols. Transfusion, 57, 1208–1217.
- Atreya, C., Glynn, S., Busch, M., Kleinman, S., Snyder, E., Rutter, S., AuBuchon, J., Flegel, W., Reeve, D., Devine, D., Cohn, C., Custer, B., Goodrich, R., Benjamin, R.J., Razatos, A., Cancelas, J., Wagner, S., Maclean, M., Gelderman, M., Cap, A. & Ness, P. (2019) Proceedings of the Food and Drug Administration public workshop on pathogen reduction technologies for blood safety 2018. Transfusion, May 29. doi: 10.1111/trf.15344.
- AuBuchon, J.P., Herschel, L., Roger, J., Taylor, H., Whitley, P., Li, J., Edrich, R. & Goodrich, R.P. (2005) Efficacy of apheresis platelets treated with riboflavin and ultraviolet light for pathogen reduction. Transfusion, 45, 1335–1341.
- Aydinok, Y., Piga, A., Origa, R., Mufti, N., Erickson, A., North, A., Waldhaus, K., Ernst, C., Lin, J.S., Huang, N., Benjamin, R.J. & Corash, L. (2019) Amustaline-glutathione pathogen-reduced red blood cell concentrates for transfusion-dependent thalassaemia. British Journal of Haematology. May 30. doi: 10.1111/bjh.15963.
- Bah, A., Cardoso, M., Seghatchian, J. & Goodrich, R.P. (2018) Reflections on the dynamics of bacterial and viral contamination of blood components and the levels of efficacy for pathogen inactivation processes. Transfusion and Apheresis Science, 57, 683–688.
- Barro, L., Drew, V.J., Poda, G.G., Tagny, C.T., El-Ekiaby, M., Owusu-Ofori, S. & Burnouf, T. (2018) Blood transfusion in sub-Saharan Africa: understanding the missing gap and responding to present and future challenges. Vox Sanguinis, 113, 726–736.
- Bashir, S., Cookson, P., Wiltshire, M., Hawkins, L., Sonoda, L., Thomas, S., Seltsam, A., Tolksdorf, F., Williamson, L.M. & Cardigan, R. (2013) Pathogen inactivation of platelets using ultraviolet C light: effect on in vitro function and recovery and survival of platelets. Transfusion, 53, 990–1000.
- Benjamin, R.J. (2006) Red blood cell pathogen reduction: in search of serological agnosticism. ISBT Science Series, 1, 222–226.
- Benjamin, R.J., Braschler, T., Weingand, T. & Corash, L.M. (2017) Hemovigilance monitoring of platelet septic reactions with effective bacterial protection systems. Transfusion, 57, 2946–2957.
- Berger, K., Bauer, M., Schopohl, D., Henschler, R. & Ostermann, H. (2013) Model calculations to quantify clinical and economic effects of pathogen inactivation in platelet concentrates. Onkologie, 36, 53–59.
- Bolton-Maggs, P.H.B., Poles, D. & on behalf of the Serious Hazards of Transfusion (SHOT) Steering Group (2018) The 2017 Annual SHOT Report. SHOT Office, Manchester, UK.
- Brixner, V., Kiessling, A.H., Madlener, K., Müller, M.M., Leibacher, J., Dombos, S., Weber, I., Pfeiffer, H.U., Geisen, C., Schmidt, M., Henschler, R., North, A., Huang, N., Mufti, N., Erickson, A., Ernst, C., Rico, S., Benjamin, R.J., Corash, L.M. & Seifried, E. (2018) Red blood cells treated with the amustaline (S-303) pathogen reduction system: a transfusion study in cardiac surgery. Transfusion, 58, 905–916.
- Busch, M.P., Bloch, E.M. & Kleinman, S. (2019) Prevention of transfusion-transmitted infections. Blood, 133, 1854–1864.
- Butler, E.K. & McCullough, J. (2018) Pathogen reduction combined with rapid diagnostic tests to reduce the risk of transfusion-transmitted infections in Uganda. Transfusion, 58, 854–861.
- Cancelas, J.A., Dumont, L.J., Rugg, N., Szczepiorkowski, Z.M., Herschel, L., Siegel, A., Pratt, P.G., Worsham, D.N., Erickson, A., Propst, M., North, A., Sherman, C.D., Mufti, N.A., Reed, W.F. & Corash, L. (2011) Stored red blood cell viability is maintained after treatment with a second-generation S-303 pathogen inactivation process. Transfusion, 51, 2367–2376.
- Cancelas, J.A., Gottschall, J.L., Rugg, N., Graminske, S., Schott, M.A., North, A., Huang, N., Mufti, N., Erickson, A., Rico, S. & Corash, L. (2017a) Red blood cell concentrates treated with the amustaline (S-303) pathogen reduction system and stored for 35 days retain post-transfusion viability: results of a two-centre study. Vox Sanguinis, 112, 210–218.
- Cancelas, J.A., Rugg, N., Fletcher, D., Pratt, P.G., Worsham, D.N., Dunn, S.K., Marschner, S., Reddy, H.L. & Goodrich, R.P. (2017b) In vivo viability of stored red blood cells derived from riboflavin plus ultraviolet light-treated whole blood. Transfusion, 51, 1460–1468.
- Cardigan, R., Turner, C. & Harrison, P. (2005) Current methods of assessing platelet function: relevance to transfusion medicine. Vox Sanguinis, 88, 153–63.
- Castrillo, A., Arcas, C., Castro, A., Adelantado, M., Tolksdorf, F. & Cabrera, J. (2009) THERAFLEX UV-Platelets: in vitro assessment of platelet quality and storage stability. Transfusion Medicine and Hemotherapy, 36, 9–47.
- Castro, E., Gironés, N., Bueno, J.L., Carrión, J., Lin, L. & Fresno, M. (2007) The efficacy of photochemical treatment with amotosalen HCl and ultraviolet A (INTERCEPT) for inactivation of Trypanosoma cruzi in pooled buffy-coat platelets. Transfusion, 47, 434–441.
- Ciaravino, V., McCullough, T. & Dayan, A.D. (2001) Pharmacokinetic and toxicology assessment of INTERCEPT (S-59 and UVA treated) platelets. Human and Experimental Toxicology, 20, 533–550.
- Ciaravino, V., Hanover, J., Lin, L., Sullivan, T. & Corash, L. (2009) Assessment of safety in neonates for transfusion of platelets and plasma prepared with amotosalen photochemical pathogen inactivation treatment by a 1-month intravenous toxicity study in neonatal rats. Transfusion, 49, 985–994.
- Cicchetti, A., Coretti, S., Sacco, F., Rebulla, P., Fiore, A., Rumi, F., Di Bidino, R., Urbina, L.I., Refolo, P., Sacchini, D., Spagnolo, A.G., Midolo, E., Marano, G., Farina, B., Pati, I., Veropalumbo, E., Pupella, S. & Liumbruno, G.M. (2018) Budget impact of implementing platelet pathogen reduction into the Italian blood transfusion system. Blood Transfusion, 16, 483–489.
- Dodd, R.Y., Foster, G.A. & Stramer, S.L. (2015) Keeping blood transfusion safe from West Nile firus: American Red Cross experience, 2003 to 2012. Transfusion Medicine Reviews, 29, 153–161.
- Drew, V.J., Barro, L., Seghatchian, J. & Burnouf, T. (2017) Towards pathogen inactivation of red blood cells and whole blood targeting viral DNA/RNA: design, technologies, and future prospects for developing countries. Blood Transfusion, 15, 512–521.
- Estcourt, L.J., Malouf, R. & Murphy, M.F. (2018) Pathogen-reduced platelets for the prevention of bleeding in people of any age. JAMA Oncology, 4, 571–572.
- Fast, L.D., DiLeone, G. & Marschner, S. (2011) Inactivation of human white blood cells in platelet products after pathogen reduction technology treatment in comparison to gamma irradiation. Transfusion, 51, 1397–1404.
- Feys, H.B., van Aelst, B. & Compernolle, V. (2019) Biomolecular consequences of platelet pathogen inactivation methods. Transfusion Medicine Reviews, 33, 29–34.
- M. Funk (Ed). (2019) Haemovigilance report of the Paul Ehrlich Institute. https://www.pei.de/haemovigilance-report, accessed on May 24th, 2019.
- Garban, F., Guyard, A., Labussière, H., Bulabois, C.E., Marchand, T., Mounier, C., Caillot, D., Bay, J.O., Coiteux, V., Schmidt-Tanguy, A., LeNiger, C., Robin, C., Ladaique, P., Lapusan, S., Deconinck, E., Rolland, C., Foote, A.M., François, A., Jacquot, C., Tardivel, R., Tiberghien, P., Bosson, J.L. & evaluation of the efficacy of platelets treated with pathogen reduction process (EFFIPAP) Study Group (2018) Comparison of the hemostatic efficacy of pathogen-reduced platelets vs untreated platelets in patients with thrombocytopenia and malignant hematologic diseases: a randomized clinical trial. JAMA Oncology, 4, 468–475.
- Garraud, O. & Lozano, M. (2018) Pathogen inactivation/reduction technologies for platelet transfusion: where do we stand? Transfusion Clinique et Biologique, 25, 165–171.
- Garraud, O., Sut, C., Haddad, A., Tariket, S., Aloui, C., Laradi, S., Hamzeh-Cognasse, H., Bourlet, T., Zeni, F., Aubron, C., Ozier, Y., Laperche, S., Peyrard, T., Buffet, P., Guyotat, D., Tavernier, E., Cognasse, F., Pozzetto, B. & Andreu, G. (2018) Transfusion-associated hazards: a revisit of their presentation. Transfusion Clinique et Biologique, 25, 118–135.
- Girona-Llobera, E., Jimenez-Marco, T., Galmes-Trueba, A., Muncunill, J., Serret, C., Serra, N. & Sedeño, M. (2014) Reducing the financial impact of pathogen inactivation technology for platelet components: our experience. Transfusion, 54, 158–168.
- Goodrich, R.P. & Segatchian, J. (2018) Special considerations for the use of pathogen reduced blood components in pediatric patients: an overview. Transfusion and Apheresis Science, 57, 374–377.
- Goodrich, R.P., Custer, B., Keil, S. & Busch, M. (2010a) Defining "adequate" pathogen reduction performance for transfused blood components. Transfusion, 50, 1827–1837.
- Goodrich, R.P., Doane, S. & Reddy, H.L. (2010b) Design and development of a method for the reduction of infectious pathogen load and inactivation of white blood cells in whole blood products. Biologicals, 38, 20–30.
- Gravemann, U., Handke, W., Müller, T.H. & Seltsam, A. (2019) Bacterial inactivation of platelet concentrates with the THERAFLEX UV-Platelets pathogen inactivation system. Transfusion, 59, 1324–1332.
- Grellier, P., Benach, J., Labaied, M., Charneau, S., Gil, H., Monsalve, G., Alfonso, R., Sawyer, L., Lin, L., Steiert, M. & Dupuis, K. (2008) Photochemical inactivation with amotosalen and long- wavelength ultraviolet light of Plasmodium and Babesia in platelet and plasma components. Transfusion, 48, 1676–1684.
- Haass, K.A., Sapiano, M.R.P., Savinkina, A., Kuehnert, M.J. & Basavaraju, S.V. (2019) Transfusion-transmitted infections reported to the National Healthcare Safety Network Hemovigilance Module. Transfusion Medicine Reviews, 33, 84–91.
- Hechler, B., Ohlmann, P., Chafey, P., Ravanat, C., Eckly, A., Maurer, E., Mangin, P., Isola, H., Cazenave, J.P. & Gachet, C. (2013) Preserved functional and biochemical characteristics of platelet components prepared with amotosalen and ultraviolet A for pathogen inactivation. Transfusion, 53, 1187–1200.
- Henschler, R., Seifried, E. & Mufti, N. (2011) Development of the S-303 pathogen inactivation technology for red blood cell concentrates. Transfusion Medicine and Hemotherapy, 38, 33–42.
- Hess, J.R., Pagano, M.B., Barbeau, J.D. & Johannson, P.I. (2016) Will pathogen reduction of blood components harm more people than it helps in developed countries? Transfusion, 56, 1236–1241.
- Irsch, J. & Lin, L. (2011) Pathogen inactivation of platelet and plasma blood components for transfusion using the INTERCEPT Blood System™. Transfusion Medicine and Hemotherapy, 38, 19–31.
- Jackman, R.P., Heitman, J.W., Marschner, S., Goodrich, R.P. & Norris, P.J. (2009) Understanding loss of donor white blood cell immunogenicity after pathogen reduction: mechanisms of action in ultraviolet illumination and riboflavin treatment. Transfusion, 49, 2686–2699.
- Janetzko, K., Cazenave, J.P., Klüter, H., Kientz, D., Michel, M., Beris, P., Lioure, B., Hastka, J., Marblie, S., Mayaudon, V., Lin, L., Lin, J.S., Conlan, M.G. & Flament, J. (2005) Therapeutic efficacy and safety of photochemically treated apheresis platelets processed with an optimized integrated set. Transfusion, 45, 1443–1452.
- Jansen, G.A., van Vliet, H.H., Vermeij, H., Beckers, E.A., Leebeek, F.W., Sonneveld, P. & van Rhenen, D.J. (2004) Functional characteristics of photochemically treated platelets. Transfusion, 44, 313–319.
- Jimenez-Marco, T., Mercant, C., Lliteras, E., Cózar, M. & Girona-Llobera, E. (2015) Practical issues that should be considered when planning the implementation of pathogen reduction technology for plateletpheresis. Transfusion and Apheresis Science, 52, 84–93.
- Jimenez-Marco, T., Garcia-Recio, M. & Girona-Llobera, E. (2018) Our experience in riboflavin and ultraviolet light pathogen reduction technology for platelets: from platelet production to patient care. Transfusion, 58, 1881–1889.
- Johnson, L., Hyland, R., Tan, S., Tolksdorf, F., Sumian, C., Seltsam, A. & Marks, D. (2016) In vitro quality of platelets with low plasma carryover treated with ultraviolet C light for pathogen inactivation. Transfusion Medicine and Hemotherapy, 43, 190–197.
- Jutzi, M., Mansouri Taleghani, B., Rueesch, M., Amsler, L. & Buser, A. (2018) Nationwide implementation of pathogen inactivation for all platelet concentrates in Switzerland. Transfusion Medicine and Hemotherapy, 45, 151–156.
- Kacker, S., Bloch, E.M., Ness, P.M., Gehrie, E.A., Marshall, C.E., Lokhandwala, P.M. & Tobian, A.A.R. (2019) Financial impact of alternative approaches to reduce bacterial contamination of platelet transfusions. Transfusion, 59, 1291–1299.
- Keil, S.D., Kiser, P., Sullivan, J.J., Kong, A.S., Reddy, H.L., Avery, A. & Goodrich, R.P. (2013) Inactivation of Plasmodium spp. in plasma and platelet concentrates using riboflavin and ultraviolet light. Transfusion, 53, 2278–2286.
- Keil, S.D., Bengrine, A., Bowen, R., Marschner, S., Hovenga, N., Rouse, L., Gilmour, D., Duverlie, G. & Goodrich, R.P. (2015a) Inactivation of viruses in platelet and plasma products using a riboflavin-and-UV-based photochemical treatment. Transfusion, 55, 1736–1744.
- Keil, S.D., Hovenga, N., Gilmour, D., Marschner, S. & Goodrich, R. (2015b) Treatment of platelet products with riboflavin and UV light: effectiveness against high titer bacterial contamination. Journal of Visualized Experiments, 102, e52820.
- Kerkhoffs, J.L., van Putten, W.L., Novotny, V.M., Te Boekhorst, P.A., Schipperus, M.R., Zwaginga, J.J., van Pampus, L.C., de Greef, G.E., Luten, M., Huijgens, P.C., Brand, A., van Rhenen, D.J. & Dutch – Belgian HOVON cooperative group (2010) Clinical effectiveness of leucoreduced, pooled donor platelet concentrates, stored in plasma or additive solution with and without pathogen reduction. British Journal of Haematology, 150, 209–217.
- Kleinman, S. & Stassinopoulos, A. (2015) Risks associated with red blood cell transfusions: potential benefits from application of pathogen inactivation. Transfusion, 55, 2983–3000.
- Knutson, F., Osselaer, J., Pierelli, L., Lozano, M., Cid, J., Tardivel, R., Garraud, O., Hervig, T., Domanovic, D., Cukjati, M., Gudmundson, S., Hjalmarsdottir, I.B., Castrillo, A., Gonzalez, R., Brihante, D., Santos, M., Schlenke, P., Elliott, A., Lin, J.S., Tappe, D., Stassinopoulos, A., Green, J. & Corash, L. (2015) A prospective, active haemovigilance study with combined cohort analysis of 19,175 transfusions of platelet components prepared with amotosalen-UVA photochemical treatment. Vox Sanguinis, 109, 343–352.
- de Korte, D., Curvers, J., de Kort, W.L., Hoekstra, T., van der Poel, C.L., Beckers, E.A. & Marcelis, H. (2006) Effects of skin disinfection method, deviation bag, and bacterial screening on clinical safety of platelet transfusions in the Netherlands. Transfusion, 46, 476–485.
- Leahy, M.F., Trentino, K.M., May, C., Swain, S.G., Chuah, H. & Farmer, S.L. (2017) Blood use in patients receiving intensive chemotherapy for acute leukemia or hematopoietic stem cell transplantation: the impact of a health system-wide patient blood management program. Transfusion, 57, 2189–2196.
- Lee, D. (2006) Perception of blood transfusion risk. Transfusion Medicine Reviews, 20, 141–148.
- Łętowska, M., Przybylska, Z., Piotrowski, D., Lachert, E., Rosiek, A., Rzymkiewicz, L. & Cardoso, M. (2016) Hemovigilance survey of pathogen-reduced blood components in the Warsaw Region in the 2009 to 2013 period. Transfusion, 56, S39–44.
- Levy, J.H., Neal, M.D. & Herman, J.H. (2018) Bacterial contamination of platelets for transfusion: strategies for prevention. Critical Care, 22, 271.
- Li, J.W., Brecher, M.E., Jacobson, J.L., Harm, S.K., Chen, D., El-Gamil, A., Dobson, A. & Mintz, P.D. (2017) Addressing the risk of bacterial contamination in platelets: a hospital economic perspective. Transfusion, 57, 2321–2328.
- Lozano, M., Galan, A., Mazzara, R., Corash, L. & Escolar, G. (2007) Leukoreduced buffy coat-derived platelet concentrates photochemically treated with amotosalen HCl and ultraviolet A light stored up to 7 days: assessment of hemostatic function under flow conditions. Transfusion, 47, 666–671.
- Lozano, M., Knutson, F., Tardivel, R., Cid, J., Maymó, R.M., Löf, H., Roddie, H., Pelly, J., Docherty, A., Sherman, C., Lin, L., Propst, M., Corash, L. & Prowse, C. (2011) A multi-centre study of therapeutic efficacy and safety of platelet components treated with amotosalen and ultraviolet A pathogen inactivation stored for 6 or 7 d prior to transfusion. British Journal of Haematology, 153, 393–401.
- Lozano, M., Cid, J., Prowse, C., McCullough, J., Klein, H.G. & Aubuchon, J.P. (2015) Pathogen inactivation or pathogen reduction: proposal for standardization of nomenclature. Transfusion, 55, 690.
- Marrocco, C., D'Alessandro, A., Girelli, G. & Zolla, L. (2013) Proteomic analysis of platelets treated with gamma irradiation versus a commercial photochemical pathogen reduction technology. Transfusion, 53, 1808–1820.
- Mays, J.A. & Hess, J.R. (2017) Modelling the effects of blood component storage lesions on the quality of haemostatic resuscitation in massive transfusion for trauma. Blood Transfusion, 15, 153–157.
- McCullough, J., Vesole, D.H., Benjamin, R.J., Slichter, S.J., Pineda, A., Snyder, E., Stadtmauer, E.A., Lopez-Plaza, I., Coutre, S., Strauss, R.G., Goodnough, L.T., Fridey, J.L., Raife, T., Cable, R., Murphy, S., Howard, F. 4th, Davis, K., Lin, J.S., Metzel, P., Corash, L., Koutsoukos, A., Lin, L., Buchholz, D.H. & Conlan, M.G. (2004) Therapeutic efficacy and safety of platelets treated with a photochemical process for pathogen inactivation: the SPRINT Trial. Blood, 104, 1534–1541.
- McCullough, J., Goldfinger, D., Gorlin, J., Riley, W.J., Sandhu, H., Stowell, C., Ward, D., Clay, M., Pulkrabek, S., Chrebtow, V. & Stassinopoulos, A. (2015) Cost implications of implementation of pathogen-inactivated platelets. Transfusion, 55, 2312–2320.
- McCullough, J., Alter, H.J. & Ness, P.M. (2019) Interpretation of pathogen load in relationship to infectivity and pathogen reduction efficacy. Transfusion, 59, 1132–1146.
- van der Meer, P.F., Ypma, P.F., van Geloven, N., van Hilten, J.A., van Wordragen-Vlaswinkel, R.J., Eissen, O., Zwaginga, J.J., Trus, M., Beckers, E.A.M., Te Boekhorst, P., Tinmouth, A., Lin, Y., Hsia, C., Lee, D., Norris, P.J., Goodrich, R.P., Brand, A., Hervig, T., Heddle, N.M., van der Bom, J.G. & Kerkhoffs, J.H. (2018) Hemostatic efficacy of pathogen-inactivated vs untreated platelets: a randomized controlled trial. Blood, 132, 223–231.
- Mirasol Clinical Evaluation Study Group (2010) A randomized controlled clinical trial evaluating the performance and safety of platelets treated with MIRASOL pathogen reduction technology. Transfusion, 50, 2362–2375.
- Mohr, H., Gravemann, U., Bayer, A. & Müller, T.H. (2009) Sterilization of platelet concentrates at production scale by irradiation with short-wave ultraviolet light. Transfusion, 49, 1956–1963.
- Muench, M.O., Heitman, J.W., Inglis, H., Fomin, M.E., Marschner, S., Goodrich, R.P., Norris, P.J. & Jackman, R.P. (2016) Reduced alloimmunization in mice following repeated transfusion with pathogen-reduced platelets. Transfusion, 56, 1419–1429.
- Mufti, N.A., Erickson, A.C., North, A.K., Hanson, D., Sawyer, L., Corash, L.M. & Lin, L. (2010) Treatment of whole blood (WB) and red blood cells (RBC) with S-303 inactivates pathogens and retains in vitro quality of stored RBC. Biologicals, 38, 14–19.
- Mundt, J.M., Rouse, L., van den Bossche, J. & Goodrich, R.P. (2014) Chemical and biological mechanisms of pathogen reduction technologies. Photochemistry and Photobiology, 90, 957–964.
- Ng, M.S.Y., Tung, J.P. & Fraser, J.F. (2018) Platelet storage lesions: what more do we know now? Transfusion Medicine Reviews, 32, 144–154.
- Norris, P.J., Kaidarova, Z., Maiorana, E., Milani, S., Lebedeva, M., Busch, M.P., Custer, B. & Rebulla, P. (2018) Ultraviolet light-based pathogen inactivation and alloimmunization after platelet transfusion: results from a randomized trial. Transfusion, 58, 1210–1217.
- North, A., Ciaravino, V., Mufti, N. & Corash, L. (2011) Preclinical pharmacokinetic and toxicology assessment of red blood cells prepared with S-303 pathogen inactivation treatment. Transfusion, 51, 2208–2218.
- Nussbaumer, W., Amato, M., Schennach, H., Astl, M., Chen, C.Y., Lin, J.S., Corash, L. & Benjamin, R.J. (2017) Patient outcomes and amotosalen/UVA-treated platelet utilization in massively transfused patients. Vox Sanguinis, 112, 249–256.
- Ohlsson, S., Diedrich, B., Uhlin, M. & Sandgren, P. (2018) Optimized processing for pathogen inactivation of double-dose buffy-coat platelet concentrates: maintained in vitro quality over 7-day storage. Vox Sanguinis, 113, 611–621.
- Osselaer, J.C., Doyen, C., Defoin, L., Debry, C., Goffaux, M., Messe, N., van Hooydonk, M., Bosly, A., Lin, J.S., Lin, L. & Corash, L. (2009) Universal adoption of pathogen inactivation of platelet components: impact on platelet and red blood cell component use. Transfusion, 49, 1412–1422.
- Perez-Pujol, S., Tonda, R., Lozano, M., Fuste, B., Lopez-Vilchez, I., Galan, A.M., Li, J., Goodrich, R. & Escolar, G. (2005) Effects of a new pathogen-reduction technology (Mirasol PRT) on functional aspects of platelet concentrates. Transfusion, 45, 911–919.
- Picker, S.M., Speer, R. & Gathof, B.S. (2004) Functional characteristics of buffy-coat PLTs photochemically treated with amotosalen-HCl for pathogen inactivation. Transfusion, 44, 320–329.
- Picker, S.M., Steisel, A. & Gathof, B.S. (2008) Effects of Mirasol PRT treatment on storage lesion development in plasma-stored apheresis-derived platelets compared to untreated and irradiated units. Transfusion, 48, 1685–1692.
- Piotrowski, D., Przybylska-Baluta, Z., Jimenez-Marco, T., Kryzauskaite, L., Papachronis, A., Marinaki, A., Höcker, P., Wilde, S.C. & Cardoso, M. (2018) Passive haemovigilance of blood components treated with a riboflavin-based pathogen reduction technology. Blood Transfusion, 16, 348–351.
- Pohler, P., Lehmann, J., Veneruso, V., Tomm, J., von Bergen, M., Lambrecht, B., Kohn, B., Weingart, C., Müller, T.H. & Seltsam, A. (2012) Evaluation of the tolerability and immunogenicity of ultraviolet C-irradiated autologous platelets in a dog model. Transfusion, 52, 2414–2426.
- Prioli, K.M., Karp, J.K., Lyons, N.M., Chrebtow, V., Herman, J.H. & Pizzi, L.T. (2018) Economic implications of pathogen reduced and bacterially tested platelet components: a US hospital budget impact model. Applied Health Economics and Health Policy, 16, 889–899.
- Prowse, C.V. (2013) Component pathogen inactivation: a critical review. Vox Sanguinis, 104, 183–199.
- Prudent, M., D'Alessandro, A., Cazenave, J.P., Devine, D.V., Gachet, C., Greinacher, A., Lion, N., Schubert, P., Steil, L., Thiele, T., Tissot, J.D., Völker, U. & Zolla, L. (2014) Proteome changes in platelets after pathogen inactivation – an interlaboratory consensus. Transfusion Medicine Reviews, 28, 72–83.
- Qadri, S.M., Chen, D., Schubert, P., Perruzza, D.L., Bhakta, V., Devine, D.V. & Sheffield, W.P. (2017) Pathogen inactivation by riboflavin and ultraviolet light illumination accelerates the red blood cell storage lesion and promotes eryptosis. Transfusion, 57, 661–673.
- Rebulla, P., Vaglio, S., Beccaria, F., Bonfichi, M., Carella, A., Chiurazzi, F., Coluzzi, S., Cortelezzi, A., Gandini, G., Girelli, G., Graf, M., Isernia, P., Marano, G., Marconi, M., Montemezzi, R., Olivero, B., Rinaldi, M., Salvaneschi, L., Scarpato, N., Strada, P., Milani, S. & Grazzini, G. (2017) Clinical effectiveness of platelets in additive solution treated with two commercial pathogen-reduction technologies. Transfusion, 57, 1171–1183.
- Reddy, H.L., Dayan, A.D., Cavagnaro, J., Gad, S., Li, J. & Goodrich, R.P. (2008) Toxicity testing of a novel riboflavin-based technology for pathogen reduction and white blood cell inactivation. Transfusion Medicine Reviews, 22, 133–153.
- Reddy, H.L., Doane, S.K., Keil, S.D., Marschner, S. & Goodrich, R.P. (2013) Development of a riboflavin and ultraviolet light-based device to treat whole blood. Transfusion, 53, 131S–136S.
- Ruane, P.H., Edrich, R., Gampp, D., Keil, S.D., Leonard, R.L. & Goodrich, R.P. (2004) Photochemical inactivation of selected viruses and bacteria in platelet concentrates using riboflavin and light. Transfusion, 44, 877–885.
- Rutter, S. & Snyder, E.L. (2019) How do we … integrate pathogen reduced platelets into our hospital blood bank inventory? Transfusion, 59, 1628–1636.
- Saá, P., Proctor, M., Foster, G., Krysztof, D., Winton, C., Linnen, J.M., Gao, K., Brodsky, J.P., Limberger, R.J., Dodd, R.Y. & Stramer, S.L. (2018) Investigational testing for Zika virus among U.S. blood donors. New England Journal of Medicine, 378, 1778–1788.
- Sachais, B.S., Paradiso, S., Strauss, D. & Shaz, B.H. (2017) Implications of the US Food and Drug Administration draft guidance for mitigating septic reactions from platelet transfusions. Blood Advances, 1, 1142–1147.
- Salunkhe, V., De Cuyper, I.M., Papadopoulos, P., van der Meer, P.F., Daal, B.B., Villa-Fajardo, M., de Korte, D., van den Berg, T.K. & Gutiérrez, L. (2019) A comprehensive proteomics study on platelet concentrates: platelet proteome, storage time and Mirasol pathogen reduction technology. Platelets, 30, 368–379.
- Sandgren, P., Tolksdorf, F., Struff, W.G. & Gulliksson, H. (2011) In vitro effects on platelets irradiated with short-wave ultraviolet light without any additional photoactive reagent using the THERAFLEX UV-Platelets method. Vox Sanguinis, 101, 35–43.
- Saris, A., Kerkhoffs, J.L., Norris, P.J., van Ham, S.M., Ten Brinke, A., Brand, A., van der Meer, P.F. & Zwaginga, J.J. (2019) The role of pathogen-reduced platelet transfusions on HLA alloimmunization in hemato-oncological patients. Transfusion, 59, 470–481.
- Schmidt, M., Geilenkeuser, W.J., Sireis, W., Seifried, E. & Hourfar, K. (2014) Emerging pathogens - how safe is blood? Transfusion Medicine and Hemotherapy, 41, 10–17.
- Schmidt, M., Hourfar, M.K., Sireis, W., Pfeiffer, U., Göttig, S., Kempf, V.A., McDonald, C.P. & Seifried, E. (2015) Evaluation of the effectiveness of a pathogen inactivation technology against clinically relevant transfusion-transmitted bacterial strains. Transfusion, 55, 2104–2012.
- Schubert, P., Culibrk, B., Karwal, S., Slichter, S.J. & Devine, D.V. (2012) Optimization of platelet concentrate quality: application of proteomic technologies to donor management. Journal of Proteomics, 76 Spec. No, 329–336.
- Schulz, W.L., McPadden, J., Gehrie, E.A., Bahar, B., Gokhale, A., Ross, R., Price, N., Spencer, B.R. & Snyder, E. (2019) Blood utilization and transfusion reactions in pediatric patients transfused with conventional or pathogen reduced platelets. Journal of Pediatrics, 209, 220–225.
- Seghatchian, J. & Tolksdorf, F. (2012) Characteristics of the THERAFLEX UV-Platelets pathogen inactivation system – an update. Transfusion and Apheresis Science, 46, 221–229.
- Seltsam, A. & Müller, T.H. (2011) UVC irradiation for pathogen reduction of platelet concentrates and plasma. Transfusion Medicine and Hemotherapy, 38, 43–54.
- Seltsam, A. & Müller, T.H. (2013) Update on the use of pathogen-reduced human plasma and platelet concentrates. British Journal of Haematology, 162, 442–454.
- Sigle, J.P., Infanti, L., Studt, J.D., Martinez, M., Sten, M., Gratwohl, A., Passweg, J., Tichelli, A. & Buser, A.S. (2013) Comparison of transfusion efficacy of amotosalen-based pathogen-reduced platelet components and gamma-irradiated platelet components. Transfusion, 53, 1788–1797.
- Sim, J., Tsoi, W.C., Lee, C.K., Leung, R., Lam, C.C.K., Koontz, C., Liu, A.Y., Huang, N., Benjamin, R.J., Vermeij, H.J., Stassinopoulos, A., Corash, L. & Lie, A.K.W. (2019) Transfusion of pathogen-reduced platelet components without leukoreduction. Transfusion, 59, 1953–1961.
- Simmons, G., Brès, V., Lu, K., Liss, N.M., Brambilla, D.J., Ryff, K.R., Bruhn, R., Velez, E., Ocampo, D., Linnen, J.M., Latoni, G., Petersen, L.R., Williamson, P.C. & Busch, M.P. (2016) High incidence of Chikungunya virus and frequency of viremic blood donations during epidemic, Puerto Rico, USA, 2014. Emerging Infectious Diseases, 22, 1221–1228.
- Slichter, S.J., Pellham, E., Bailey, S.L., Christoffel, T., Gettinger, I., Gaur, L., Latchman, Y., Nelson, K. & Bolgiano, D. (2017) Leukofiltration plus pathogen reduction prevents alloimmune platelet refractoriness in a dog transfusion model. Blood, 130, 1052–1061.
- Snyder, E., Raife, T., Lin, L., Cimino, G., Metzel, P., Rheinschmidt, M., Baril, L., Davis, K., Buchholz, D.H., Corash, L. & Conlan, M.G. (2004) Recovery and life span of 111indium-radiolabeled platelets treated with pathogen inactivation with amotosalen HCl (S-59) and ultraviolet A light. Transfusion, 44, 1732–1740.
- Snyder, E., McCullough, J., Slichter, S.J., Strauss, R.G., Lopez-Plaza, I., Lin, J.S., Corash, L., Conlan, M.G., SPRINT Study Group (2005) Clinical safety of platelets photochemically treated with amotosalen HCl and ultraviolet A light for pathogen inactivation: the SPRINT trial. Transfusion, 45, 1864–1875.
- Spindler-Raffel, E., Benjamin, R.J., McDonald, C.P., Ramirez-Arcos, S., Aplin, K., Bekeredjian-Ding, I., de Korte, D., Gabriel, C., Gathof, B., Hanschmann, K.M., Hourfar, K., Ingram, C., Jacobs, M.R., Keil, S.D., Kou, Y., Lambrecht, B., Marcelis, J., Mukhtar, Z., Nagumo, H., Niekerk, T., Rojo, J., Marschner, S., Satake, M., Seltsam, A., Seifried, E., Sharafat, S., Störmer, M., Süßner, S., Wagner, S.J., Yomtovian, R. & ISBT Working Party Transfusion-Transmitted Infectious Diseases (WP-TTID), Subgroup on Bacteria (2017) Enlargement of the WHO international repository for platelet transfusion-relevant bacteria reference strains. Vox Sanguinis, 112, 713–722.
- Staginnus, U. & Corash, L. (2004) Economics of pathogen inactivation technology for platelet concentrates in Japan. International Journal of Hematology, 80, 317–324.
- Stivala, S., Gobbato, S., Infanti, L., Reiner, M.F., Bonetti, N., Meyer, S.C., Camici, G.G., Lüscher, T.F., Buser, A. & Beer, J.H. (2017) Amotosalen/ultraviolet A pathogen inactivation technology reduces platelet activatability, induces apoptosis and accelerates clearance. Haematologica, 102, 1650–1660.
- Stolla, M. (2019) Pathogen reduction and HLA alloimmunization: more questions than answers. Transfusion, 59, 1152–1155.
- Thiele, T., Pohler, P., Kohlmann, T., Sümnig, A., Aurich, K., Selleng, K., Westphal, A., Bakchoul, T., Petersmann, A., Müller, T.H., Greinacher, A. & Seltsam, A. (2015) Tolerance of platelet concentrates treated with UVC-light only for pathogen reduction–a phase I clinical trial. Vox Sanguinis, 109, 44–51.
- Thomas, K.A., Shea, S.M., Yazer, M.H. & Spinella, P.C. (2019) Effect of leukoreduction and pathogen reduction on the hemostatic function of whole blood. Transfusion, 59, 1539–1548.
- Tormey, C.A., Santhanakrishnan, M., Smith, N.H., Liu, J., Marschner, S., Goodrich, R.P. & Hendrickson, J.E. (2016) Riboflavin-ultraviolet light pathogen reduction treatment does not impact the immunogenicity of murine red blood cells. Transfusion, 56, 863–872.
- Trakhtman, P., Kumukova, I., Starostin, N., Borsakova, D., Balashov, D., Ignatova, A., Kadaeva, L., Novichkova, G. & Rumiantcev, A. (2019) The pathogen-reduced red blood cell suspension: single centre study of clinical safety and efficacy in children with oncological and haematological diseases. Vox Sanguinis, 114, 223–231.
- Vostal, J.G. (2006) Efficacy evaluation of current and future platelet transfusion products. Journal of Trauma, 60, S78–82.
- Wagner, S.J. (2011) Developing pathogen reduction technologies for RBC suspensions. Vox Sanguinis, 100, 112–121.
- Wagner, S.J. & Getz, T.M. (2019) Is a platelet suntan the answer? Transfusion, 59, 1163–1165.
- Ware, A.D., Jacquot, C., Tobian, A.A.R., Gehrie, E.A., Ness, P.M. & Bloch, E.M. (2018) Pathogen reduction and blood transfusion safety in Africa: strengths, limitations and challenges of implementation in low-resource settings. Vox Sanguinis, 113, 3–12.
- Weimer, A., Tagny, C.T., Tapko, J.B., Gouws, C., Tobian, A.A.R., Ness, P.M. & Bloch, E.M. (2019) Blood transfusion safety in sub-Saharan Africa: a literature review of changes and challenges in the 21st century. Transfusion, 59, 412–427.
- Yonemura, S., Doane, S., Keil, S., Goodrich, R., Pidcoke, H. & Cardoso, M. (2017) Improving the safety of whole blood-derived transfusion products with a riboflavin-based pathogen reduction technology. Blood Transfusion, 15, 357–364.
- Yoshida, T., Prudent, M. & D'Alessandro, A. (2019) Red blood cell storage lesion: causes and potential clinical consequences. Blood Transfusion, 17, 27–52.
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