Pathogen reduction technology treatment of platelets, plasma and whole blood using riboflavin and UV light

Transfusion Medicine and Hemotherapy

Volumn 38, Issue 1, 2011, Pages 8-18

  Marschner, Susanne ^a   Goodrich, Raymond ^a  

^a CaridianBCT Biotechnologies   (United States)

Author keywords

Pathogen reduction; Riboflavin; Transfusion safety

Indexed keywords

GUANINE; LUMICHROME; MITOCHONDRIAL DNA; NUCLEIC ACID; PHOTOSENSITIZING AGENT; RIBOFLAVIN;

ACINETOBACTER BAUMANNII; ARTICLE; BABESIOSIS; BACILLUS CEREUS; BACTERIUM CONTAMINATION; BLOOD; BLOOD COMPONENT; BLOOD DONOR; BLOOD SAFETY; BLOOD TRANSFUSION; BLOOD TRANSFUSION REACTION; CHAGAS DISEASE; CHIKUNGUNYA ALPHAVIRUS; CLINICAL EVALUATION; COST EFFECTIVENESS ANALYSIS; CYTOMEGALOVIRUS; DISEASE TRANSMISSION; ENTEROBACTER CLOACAE; ENZYME DENATURATION; ESCHERICHIA COLI; GAMMA IRRADIATION; HEPATITIS B VIRUS; HEPATITIS C VIRUS; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN PARVOVIRUS B19; INFECTION PREVENTION; INFECTION RISK; INFECTION SENSITIVITY; INFLUENZA VIRUS; KLEBSIELLA PNEUMONIAE; LEISHMANIASIS; LIGHT ABSORPTION; MALARIA; MICROBIOLOGICAL PHENOMENA AND FUNCTIONS; MICROORGANISM DETECTION; NEWBORN JAUNDICE; PATHOGEN REDUCTION TECHNOLOGY SYSTEM; PHOTOTHERAPY; PLASMA; PROPIONIBACTERIUM ACNES; QUALITY CONTROL; RABIES VIRUS; SCRUB TYPHUS; SENSITIVITY AND SPECIFICITY; SERRATIA MARCESCENS; STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS EPIDERMIDIS; STREPTOCOCCUS AGALACTIAE; STREPTOCOCCUS MITIS; STREPTOCOCCUS PYOGENES; TECHNOLOGY; THROMBOCYTE; TOXICOLOGY; ULTRAVIOLET RADIATION; VIRUS INACTIVATION; WEST NILE FEVER; YERSINIA ENTEROCOLITICA;

EID: 79851470298     PISSN: 16603796     EISSN: None     Source Type: Journal    
DOI: 10.1159/000324160     Document Type: Article

References (91)

1. Klein HG: Will blood transfusion ever be safe enough? JAMA 2000;284:238-240. (Pubitemid 30460870)
2. Moor AC, Dubbelman TM, VanSteveninck J, Brand A: Transfusion-transmitted diseases: risks, preven-tion and perspectives. Eur J Haematol 1999;62:1-18. (Pubitemid 29029912)
3. Goodrich RP, Platz MS: The design and develop-ment of selective, photoactivated drugs for steri-lization of blood products; Drugs Future 1997;22: 159-171. (Pubitemid 27186607)
4. Kasai H, Yamaizumi Z, Yamamoto F, Bessho T, Nishimura S, Berger M, Cadet J: Photosensitized formation of 8-hydroxyguanine (7,8-dihydro-8-oxoguanine) in DNA by riboflavin. Nucleic Acids Symp Ser 1992;181-182.
5. Korycka-Dahl M, Richardson T: Photodegrada-tion of DNA with fluorescent light in the presence of riboflavin, and photoprotection by flavin triplet-state quenchers. Biochim Biophys Acta 1980;610: 229-234.
6. Kuratomi K, Kobayashi Y: Studies on the interac-tions between DNA and flavins. Biochim Biophys Acta 1977;476:207-217.
7. Peak JG, Peak MJ, MacCoss M: DNA breakage caused by 334-nm ultraviolet light is enhanced by naturally occurring nucleic acid components and nucleotide coenzymes. Photochem Photobiol 1984; 39:713-716.
8. Speck WT, Rosenkranz HS: Phototherapy for neonatal hyperbilirubinemia-a potential environ-mental health hazard to newborn infants: a review. Environ Mutagen 1979;1:321-336. (Pubitemid 10060807)
9. Kumar V, Lockerbie O, Keil SD, Ruane PH, Platz MS, Martin CB, Ravanat JL, Cadet J, Goodrich RP: Riboflavin and UV-light based pathogen re-duction: extent and consequence of DNA damage at the molecular level. Photochem Photobiol 2004; 80:15-21.
10. Goodrich RP, Edrich RA, Goodrich L, Scott C, Manica K, Hlavinka D, Hovenga N, Hansen E, Gampp D, Keil SD, Gilmour DI, Li J, Martin CB, Platz MS: The antiviral and antibacterial properties of riboflavin and light: applications to blood safety and transfusion medicine; in Silva E, Edwards AM, (eds): Flavins: Photochemistry and Photobiology. Comprehensive Series in Photochemical and Pho-tobiological Sciences. Cambridge, The Royal Soci-ety of Chemistry, 2006, pp 83-113.
11. Janetzko K, Hinz K, Marschner S, Klüter H, Bugert P: Monitoring of the Mirasol Pathogen Reduction Procedure for Platelet Concentrates by PCR and bioanalyzer; Transfus Med Hemother 2007;34(suppl 1):S60.
12. Martin CB, Wilfong E, Ruane P, Goodrich R, Platz M: An action spectrum of the riboflavin-photosen-sitized inactivation of lambda phage. Photochem Photobiol 2005;81:474-480. (Pubitemid 40551528)
13. Hayashi M, Kishi M, Sofuni T, Ishidate M Jr: Micronucleus tests in mice on 39 food additives and eight miscellaneous chemicals. Food Chem Toxicol 1988;26:487-500.
14. Munoz N, Hayashi M, Bang LJ, Wahrendorf J, Crespi M, Bosch FX: Effect of riboflavin, retinol, and zinc on micronuclei of buccal mucosa and of esophagus: a randomized double-blind intervention study in China. J Natl Cancer Inst 1987;79:687-691. (Pubitemid 17145696)
15. Studer A, Zbinden G, Uehlinger E: Die Pathologie der Avitaminosen and Hypervitaminosen; in Buch-ner F, Letterer E, Roulet F (Hrsg): Handbuch der Allgemeinen Pathologie. Berlin, Springer, 1962, pp 734-987.
16. Unna K, Greslin JG: Studies on the toxicity and pharmacology of riboflavin. J Pharmacol 1942; 76:75-80.
17. Bates CJ: Human requirements for riboflavin. Am J Clin Nutr 1987;46:122-123.
18. Kostenbauder HB, DeLuca PP, Kowarski CR: Photobinding and photoreactivity of riboflavin in the presence of macromolecules. J Pharm Sci 1965;54:1243-1251.
19. Sisson TR: Photodegradation of riboflavin in ne-onates. Federation Proc 1987;46:1883-1885.
20. Yurdakok M, Erdem G, Tekinalp G: Riboflavin in the treatment of neonatal hyperbilirubinemia. Turkish J Pediatr 1988;30:159-161. (Pubitemid 19146383)
21. Olsen JH, Hertz H, Kjaer SK, Bautz A, Mellem-kjaer L, Boice JD Jr: Childhood leukemia follow-ing phototherapy for neonatal hyperbilirubinemia (Denmark). Cancer Causes Control 1996;7:411-414. (Pubitemid 26228329)
22. Hardwick CC, Herivel TR, Hernandez SC, Ruane PH, Goodrich RP: Separation, identification and quantification of riboflavin and its photoproducts in blood products using high-performance liquid chromatography with fluorescence detection: a method to support pathogen reduction technology. Photochem Photobiol 2004;80:609-615 (Pubitemid 40174493)
23. Expert Group on Vitamins and Minerals: Revised review of riboflavin:. 2002, pp 1-48. www.food.gov.uk/multimedia/pdfs/reviewriboflavin.
24. BIBRA Working Group: Riboflavin and its de-rivatives: toxicity profile. Epscm, Surrey, BIBRA, 1990, pp 1-7.
25. Reddy H, Buytaert-Hoefen K, Hovenga N, Gampp D, White J, Goodrich R: Acute toxicity of Mira-sol PRT-treated FFP in plasma exchange in dogs. Transfusion 2007;47(suppl):P75A.
26. Reddy HL, Dayan AD, Cavagnaro J, Gad S, Li J, Goodrich RP: Toxicity testing of a novel ribofla-vin-based technology for pathogen reduction and white blood cell inactivation. Transfus Med Rev 2008;22:133-153. (Pubitemid 351384824)
27. Ambruso DR, Thurman G, Marschner S, Goodrich RP: Lack of antibody formation to platelet neo-antigens after transfusion of riboflavin and ultra-violet light-treated platelet concentrates. Transfu-sion 2009;49:2631-2636.
28. Goodrich R, Murthy K, Doane S, Fitzpatrick C, Morrow L, Arndt P, Reddy H, Buytaert-Hoefen K, Garraty G: Evaluation of potential immune re-sponse and in vivo survival of riboflavin-ultraviolet light-treated red blood cells in baboons. Transfu-sion 2009;49:64-74.
29. Silliman CC, Khan SY, Ball JB, Kelher MR, Marschner S: Mirasol Pathogen Reduction Tech-nology treatment does not affect acute lung inju-ry in a two-event in vivo model caused by stored blood components. Vox Sang 2010;98:525-530.
30. Levy R, Herzberg GR, Andrews WL, Sutradhar B, Friel JK: Thiamine, riboflavin, folate, and vitamin B12 status of low birth weight infants receiving parenteral and enteral nutrition. JPEN J Parenter Enteral Nutr 1992;16:241-247.
31. Goodrich RP, Custer B, Keil S, Busch M: Defin-ing adequate pathogen reduction performance for transfused blood components. Transfusion 2010; 50:1827-1837.
32. McDonald CP, Roy A, Mahajan P, Smith R, Char-lett A, Barbara JA: Relative values of the inter-ventions of diversion and improved donor-arm disinfection to reduce the bacterial risk from blood transfusion. Vox Sang 2004;86:178-182. (Pubitemid 38529507)
33. Brecher ME, Hay SN: Bacterial contamination of blood components. Clin Microbiol Rev 2005;18: 195-204. (Pubitemid 40170668)
34. Goodrich RP, Gilmour D, Hovenga N, Keil SD: A laboratory comparison of pathogen reduction tech-nology treatment and culture of platelet products for addressing bacterial contamination concerns. Transfusion 2009;49:1205-1216.
35. Fast LD, DiLeone G, Cardarelli G, Li J, Goodrich R: Mirasol PRT treatment of donor white blood cells prevents the development of xenogeneic graft-versus-host disease in Rag2-/-gamma c-/-dou-ble knockout mice. Transfusion 2006;46:1553-1560. (Pubitemid 44326331)
36. Fast LD, DiLeone G, Marschner S: Inactivation of human white blood cells in platelet products after pathogen reduction technology treatment in com-parison to gamma irradiation. Transfusion 2010; doi: 10.1111/j.1537-2995. 2010.02984.x.
37. Marschner S, Fast LD, Baldwin WM III, Slichter SJ, Goodrich RP: White blood cell inactivation after treatment with riboflavin and ultraviolet light. Transfusion 2010;50:2489-2498.
38. Jackman R, Heitman J, Marschner S, Goodrich R, Norris PJ: Understanding loss of donor white blood cell immunogenicity following pathogen reduction: mechanisms of action in UV illumination and ribo-flavin treatment; Transfusion 2009;49:2686-2699.
39. Asano H, Lee CY, Fox-Talbot K, Koh CM, Erdinc MM, Marschner S, Keil S, Goodrich RP, Baldwin WM: Treatment with riboflavin and ultraviolet light prevents alloimmunization to platelet trans-fusions and cardiac transplants. Transplantation 2007;84:1174-1182. (Pubitemid 350125361)
40. Goodrich RP, Li J, Pieters H, Crookes R, Roodt J, Heyns A: Correlation of in vitro platelet qual-ity measurements with in vivo platelet viability in human subjects. Vox Sang 2006;90:279-285.
41. Marschner S, Hovenga N, Goodrich RP: Coagu-lation potential of Mirasol Pathogen Reduction technology treated platelets. Vox Sang 2010;99:247.
42. Perez-Pujol S, Tonda R, Lozano M, Fuste B, Lopez-Vilchez I, Galan AM, Li J, Goodrich R, Escolar G: Effects of a new pathogen-reduction technology (Mirasol PRT) on functional aspects of platelet concentrates. Transfusion 2005;45:911-919. (Pubitemid 40798782)
43. Picker SM, Schneider V, Gathof BS: Platelet func-tion assessed by shear-induced deposition of split triple-dose apheresis concentrates treated with pa-tho gen reduction technologies. Transfusion 2009; 49:1224-1232.
44. Li J, Lockerbie O, de KD, Rice J, McLean R, Goodrich RP: Evaluation of platelet mitochondria integrity after treatment with Mirasol pathogen re-duction technology. Transfusion 2005;45:920-926. (Pubitemid 40798783)
45. Picker SM, Schneider V, Oustianskaia L, Gathof BS: Cell viability during platelet storage in correla-tion to cellular metabolism after different pathogen reduction technologies. Transfusion 2009;49:2311-2318.
46. Hockberger PE, Skimina TA, Centonze VE, Lavin C, Chu S, Dadras S, Reddy JK, White JG: Activation of flavin-containing oxidases underlies light-induced production of H2O2 in mammalian cells. Proc Natl Acad Sci USA 1999;96:6255-6260. (Pubitemid 29256652)
47. Marschner S, Hovenga N, Gathof BS, Picker SM, de Korte D, Goodrich R: Acetate consumption in platelets treated with different pathogen reduction technologies. Vox Sang 2010;99:247.
48. Akkerman J-W, Verhoeven AJ: Energy Metabo-lism and Function; in Holmsen H (ed): Platelet Re-sponses and Metabolism. Vol. 3: Response-Metab-olism Relationships. Boca Raton, CRC Press, 1987, pp 69-99.
49. Kerkhoffs JL, van Putten WL, Novotny VM, Te Boekhorst PA, Schipperus MR, Zwaginga JJ, van Pampus LC, de Greef GE, Luten M, Huijgens PC, Brand A, van Rhenen DJ: Clinical effectiveness of leucoreduced, pooled donor platelet concen-trates, stored in plasma or additive solution with and without pathogen reduction. Br J Haematol 2010;150:209-217.
50. Cazenave JP, Folléa G, Bardiaux L, Boiron JM, Lafeuillade B, Debost M, Lioure B, Harousseau JL, Tabrizi R, Cahn JY, Michallet M, Ambruso D, Schots R, Tissot JD, Sensebé L, Kondo T, McCullough J, Rebulla P, Escolar G, Mintz P, Heddle NM, Goodrich RP, Bruhwyler J, Le C, Cook RJ, Stouch B; for members of the The Mirasol Clinical Evaluation Study Group: A randomized controlled clinical trial evaluating the performance and safety of platelets treated with MIRASOL pathogen reduc tion technology: Transfusion 2010;50:2362-2375.
51. British Committee for Standards in Haematol-ogy, Blood Transfusion Task Force: Guidelines for the use of platelet transfusions: Br J Haematol 2003;122:10-23.
52. Solheim BG, Seghatchian J: Update on pathogen reduction technology for therapeutic plasma: an overview. Transfus Apher Sci 2006;35:83-90. (Pubitemid 44354323)
53. Cardigan R, Lawrie AS, Mackie IJ, Williamson LM: The quality of fresh-frozen plasma produced from whole blood stored at 4 degrees C overnight. Transfusion 2005;45:1342-1348. (Pubitemid 41647802)
54. Keitel S (ed): Guide to the Preparation, Use and Quality Assurance of Blood Components Stras-bourg, Council of Europe, 2009, pp 256-258.
55. Hornsey VS, Drummond O, Morrison A, McMil-lan L, MacGregor IR, Prowse CV: Pathogen reduction of fresh plasma using riboflavin and ultra-violet light: effects on plasma coagulation proteins. Transfusion 2009;49:2167-2172.
56. Larrea L, Calabuig M, Roldan V, Rivera J, Tsai HM, Vicente V, Roig R: The influence of ribofla-vin photochemistry on plasma coagulation factors. Transfus Apher Sci 2009;41:199-204.
57. Smith J, Rock G: Protein quality in Mirasol patho-gen reduction technology-treated, apheresis-derived fresh-frozen plasma. Transfusion 2010;50:926-931.
58. Bihm D, Ettinger A, Buytaert-Hoefen K, Hen-drix B, Maldonado-Codina G, Rock G, Giclas P, Goodrich RP: Characterization of plasma protein activity in riboflavinand UV light-treated fresh fro-zen plasma during 2 years of storage at-30 °C. Vox Sang 2010;98:108-115.
59. Ettinger A, Miklauz MM, Hendrix B, Bihm D, Maldonado-Codina G, Goodrich RP: Protein sta-bility of previously frozen plasma, riboflavin and UV light-treated, refrozen and stored for up to 2 years at-30 °C. Transfus Apher Sci 2010;(in press).
60. Antic A, Stanijkovic Z: Clinical performance of buffy coat platelets treated with riboflavin and UV light. Transfusion 2010;50(suppl):p66A.
61. Cancelas J, Rugg N, Worsham DN, Pratt GP, Dunn SK, Reddy H, Fletcher D, Goodrich RP: Quality assessment of stored RBC after treatment of whole blood with the Mirasol System. Transfu-sion 2010;50(suppl):p71A.
62. Goodrich RP, Doane S, Reddy HL: Design and development of a method for the reduction of in-fectious pathogen load and inactivation of white blood cells in whole blood products. Biologicals 2010;38:20-30.
63. Li J, Goodrich L, Hansen E, Edrich R, Gampp D, Goodrich RP: Platelet glycolytic flux increases stimulated by ultraviolet-induced stress is not the direct cause of platelet morphology and activation changes: possible implications for the role of glu-cose in platelet storage. Transfusion 2005;45:1750-1758. (Pubitemid 43923902)
64. Reddy H, Marschner S, Doane S, Spotts C, Good-rich RP: Room temperature storage of whole blood treated with the Mirasol System. Vox Sang 2010;99:p243.
65. Reddy H, Doane S, Spotts C, Goodrich RP: In vitro assessments of platelet function in whole blood treated with the Mirasol System and stored at room temperature. Vox Sang 2010;99:p243.
66. Tonnetti L, Thorp AM, Reddy H, Goodrich RP, Leiby DA: Evaluation of the reduction of T cruzi with the Mirasol System for Whole Blood. Transfu-sion 2010;50(suppl):p209A.
67. Custer B, Agapova M, Martinez RH: The cost-effectiveness of pathogen reduction technology as assessed using a multiple risk reduction model. Transfusion 2010;50:2461-2473.
68. Jackson BR, Busch MP, Stramer SL, AuBuchon JP: The cost-effectiveness of NAT for HIV, HCV, and HBV in whole-blood donations. Transfusion 2003;43:721-729. (Pubitemid 36629116)
69. Marshall DA, Kleinman SH, Wong JB, AuBuchon JP, Grima DT, Kulin NA, Weinstein MC: Cost-effectiveness of nucleic acid test screening of vol-unteer blood donations for hepatitis B, hepatitis C and human immunodeficiency virus in the United States. Vox Sang 2004;86:28-40. (Pubitemid 38200453)
70. Heddle NM: Optimal timing and dosing of platelet transfusions. ISBT Science Series 2010;5:88-94.
71. Prowse C: Properties of pathogen-inactivated plas-ma components. Transfus Med Rev 2009;23:124-133.
72. Rock G: A comparison of methods of pathogen inactivation of FFP. Vox Sang 2010; DOI: 10.1111/j.1423-0410.2010.01374.x.
73. Alter HJ: Pathogen reduction: a precautionary principle paradigm. Transfus Med Rev 2008;22:97-102. (Pubitemid 351381952)
74. Cardo LJ, Rentas FJ, Ketchum L, Salata J, Har-man R, Melvin W, Weina PJ, Mendez J, Reddy H, Goodrich R: Pathogen inactivation of Leishmania donovani infantum in plasma and platelet concen-trates using riboflavin and ultraviolet light. Vox Sang 2006;90:85-91. (Pubitemid 43381495)
75. Cardo LJ, Salata J, Mendez J, Reddy H, Goodrich R: Pathogen inactivation of Trypanosoma cruzi in plasma and platelet concentrates using ribofla-vin and ultraviolet light. Transfus Apher Sci 2007; 37:131-137. (Pubitemid 350181574)
76. Rentas F, Harman R, Gomez C, Salata J, Childs J, Silva T, Lippert L, Montgomery J, Richards A, Chan C, Jiang J, Reddy H, Li J, Goodrich R: In-activation of Orientia tsutsugamushi in red blood cells, plasma, and platelets with riboflavin and light, as demonstrated in an animal model. Transfusion 2007;47:240-247. (Pubitemid 46146557)
77. Sullivan J, Bounngaseng A, Reddy H, Keil S, Goodrich RP: Inactivation of Plasmodium falci-parum in plasma and platelet concentrates with riboflavin and UV light. Vox Sang 2008;95:p278.
78. Tonnetti L, Proctor MC, Reddy HL, Goodrich RP, Leiby DA: Evaluation of the Mirasol pathogen [corrected] reduction technology system against Babesia microti in apheresis platelets and plasma. Transfusion 2010;50:1019-1027.
79. Fast LD, DiLeone G, Li J, Goodrich R: Functional inactivation of white blood cells by Mirasol treat-ment. Transfusion 2006;46:642-648.
80. Li J, de Korte D, Woolum MD, Ruane PH, Keil SD, Lockerbie O, McLean R, Goodrich RP: Patho-gen reduction of buffy coat platelet concentrates using riboflavin and light: comparisons with path-ogen-reduction technology-treated apheresis plate-let products. Vox Sang 2004;87:82-90. (Pubitemid 39265454)
81. Ostrowski SR, Bochsen L, Salado-Jimena JA, Ullum H, Reynaerts I, Goodrich RP, Johansson PI: In vitro cell quality of buffy coat platelets in addi-tive solution treated with pathogen reduction tech-nology. Transfusion 2010;50:2210-2219.
82. Picker SM, Steisel A, Gathof BS: Effects of Mira-sol PRT treatment on storage lesion development in plasma-stored apheresis-derived platelets com-pared to untreated and irradiated units. Transfusion 2008;48:1685-1692.
83. Picker SM, Oustianskaia L, Schneider V, Gathof BS: Functional characteristics of apheresis-derived platelets treated with ultraviolet light combined with either amotosalen-HCl (S-59) or riboflavin (vitamin B2) for pathogen-reduction. Vox Sang 2009;97:26-33.
84. Picker SM, Oustianskaia L, Schneider V, Gathof BS: Annexin V release and transmembrane mi-tochondrial potential during storage of apheresis-derived platelets treated for pathogen reduction. Transfus Med Hemother 2010;37:7-12.
85. Ruane PH, Edrich R, Gampp D, Keil SD, Leon-ard RL, Goodrich RP: Photochemical inactivation of selected viruses and bacteria in platelet concen-trates using riboflavin and light. Transfusion 2004; 44:877-885. (Pubitemid 38738418)
86. Picker SM, Steisel A, Gathof BS: Cell integrity and mitochondrial function after Mirasol-PRT treat-ment for pathogen reduction of apheresis-derived platelets: Results of a three-arm in vitro study. Transfus Apher Sci 2009;40:79-85.
87. Galan AM, Lozano M, Molina P, Navalon F, Marschner S, Goodrich R, Escolar G: Impact of pathogen reduction technology and storage in platelet additive solutions on platelet function. Transfusion 2010; doi: 10.1111/j.1537-2995.2010. 02914.x.
88. Cardoso M, Piotrowski D, Przybylska-Baluta Z, Leleno M, Uszynska A: Transfusion experience with platelet concentrates treated with the Mirasol PRT System in the regional BTS Warsaw. Transfusion 2010;50(suppl):p67A.
89. Marschner S, Villaescusa RD, Perez Vaquero MA, De Fusco G, Arroyo L, Pierelli L, Nucci S, Freitas A: The Mirasol Evaluation Program: use of Mirasol Pathogen Reduction Technologyfor platelets in routine clinical practice. Vox Sang 2009;96(suppl 1):229.
90. Stanojkovic ZA, Antic AM, Stanijkovic M: Clini-cal performance of buffy coat platelets treated with riboflavin and UV light. Transfusion 2010;50 (suppl):p66A.
91. Yanez M, Blanco L, Gonzalez A, Moya A, De Coca G, Cuello R: Performance of buffy coat platelets in plasma treated with riboflavin and UV light: in vitro and in vivo evaluation. Transfusion 2010;50(suppl):p84A.