Pathogen reduction using riboflavin and UV light explained

Pathogen reduction using riboflavin and UV light is a method by which infectious pathogens in blood for transfusion are inactivated by adding riboflavin and irradiating with UV light.^{[1] [2] [3]} This method reduces the infectious levels of disease-causing agents that may be found in donated blood components, while still maintaining good quality blood components for transfusion. This type of approach to increase blood safety is also known as “pathogen inactivation” in the industry.

Despite measures that are in place in the developed world to ensure the safety of blood products for transfusion, a risk of disease transmission still exists. Consequently, the development of pathogen inactivation/reduction technologies for blood products has been an ongoing effort in the field of transfusion medicine. A new procedure for the treatment of individual units of single-donor (apheresis) or whole blood–derived, pooled, platelets has recently been introduced. This technology uses riboflavin and light for the treatment of platelets and plasma.

Method

This pathogen reduction process involves adding riboflavin (vitamin B2) to the blood component, which is then placed into an illuminator where it is exposed to UV light for about five to ten minutes. Exposure to UV light activates riboflavin and when it is associated with nucleic acids (DNA and RNA), riboflavin causes a chemical alteration to functional groups of the nucleic acids thereby making pathogens unable to replicate.^{[1] [4] [5]} In this way the process prevents viruses, bacteria, parasites and white blood cells, from replicating and causing disease.^{[6] [7]}

UV Light + Riboflavin → Irreversible Inactivation

This method using riboflavin and UV light renders pathogens harmless by using a non-mutagenic, non-toxic method. Riboflavin and its photoproducts are already present in the human body and do not need to be removed from blood products prior to transfusion.^[1]

Examples of pathogens inactivated by this method

• Viruses – both enveloped and non-enveloped^[8] including: Avian Flu, Chikungunya, CMV, Hepatitis A, Hepatitis B, Hepatitis C, HIV, Human B-19, Influenza, Rabies, and West Nile.^[5] This adds a level of protection for those receiving the transfusion product against viruses that donors are screened for (and may be at a level too low to be detected- window period) as well as those that they are not screened for at the time of their donation.
• Bacteria – such as: B. cereus, E. cloacae, E. coli, K. pneumonia, P. acnes, S. marcescens, S. aureus, S. epidermidis, S. agalactiae, S. mitis, S. pyogenes, and Y. enterocolitica.^[5]
• Parasites – including: Babesiosis, Chagas disease, Leishmaniasis, Malaria, and Scrub typhus.^{[2] [9]}
• White blood cells – due to the effective inactivation of white blood cells in donated blood products, riboflavin and UV light treatment may be used as an alternative to gamma-irradiation for the prevention of transfusion-associated graft-versus-host disease (TA-GVHD),^[7] a serious blood transfusion related complication.

Application

The riboflavin and UV light method for pathogen reduction of platelets and plasma is in routine use in multiple countries throughout Europe.^{[10] [11] [12] [13]} This same process is currently in development for the treatment of whole blood, resulting in pathogen reduction of the three components (RBCs, platelets and plasma).

Notes and References

1. 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. . 80 . 3 . 609–15 . 2004 . 15382964 . 10.1562/0031-8655(2004)080<0609:TNSIAQ>2.0.CO;2 . 198154059 . 0031-8655 .
2. Sullivan J, etal . Pathogen Inactivation of plasmodium Falciparum in Plasma and Platelet Concentrations with Riboflavin and UV Light . Vox Sanguinis . 2008 . 95 . Suppl. 1 . 278–279 . 10.1111/j.1423-0410.2008.01056.x . 10292/2147 . free .
3. Reddy HL, Dayan AD, Cavagnaro J, Gad S, Li J, Goodrich RP . Toxicity testing of a novel riboflavin-based technology for pathogen reduction and white blood cell inactivation . Transfus Med Rev . 22 . 2 . 133–53 . April 2008 . 18353253 . 10.1016/j.tmrv.2007.12.003 .
4. Larrea L, Calabuig M, Roldán V, Rivera J, Tsai HM, Vicente V, Roig R . The influence of riboflavin photochemistry on plasma coagulation factors . Transfus. Apher. Sci. . 41 . 3 . 199–204 . December 2009 . 19782644 . 10.1016/j.transci.2009.09.006 . 3158998.
5. Ruane PH, Edrich R, Gampp D, Keil SD, Leonard RL, Goodrich RP . Photochemical inactivation of selected viruses and bacteria in platelet concentrates using riboflavin and light . Transfusion . 44 . 6 . 877–85 . June 2004 . 15157255 . 10.1111/j.1537-2995.2004.03355.x . 24109912 .
6. Book: Goodrich RP, etal . Edwards, Ana M. . Silva, Eduardo . Flavins: photochemistry and photobiology . RSC Publishing . Cambridge . 2006 . Chapter 5:The Antiviral and Antibacterial Properties of Riboflavin and Light: Applications to Blood Safety and Transfusion Medicine . 0-85404-331-4 .
7. Fast LD, Dileone G, Marschner S . Inactivation of human white blood cells in platelet products after pathogen reduction technology treatment in comparison to gamma irradiation . Transfusion . 51. 7. 1397–1404. December 2010 . 21155832 . 10.1111/j.1537-2995.2010.02984.x . 34154946 .
8. Goodrich RP, Custer B, Keil S, Busch M . Defining "adequate" pathogen reduction performance for transfused blood components . Transfusion . 50 . 8 . 1827–37 . August 2010 . 20374558 . 10.1111/j.1537-2995.2010.02635.x . 11538115 .
9. Cardo LJ, Salata J, Mendez J, Reddy H, Goodrich R . Pathogen inactivation of Trypanosoma cruzi in plasma and platelet concentrates using riboflavin and ultraviolet light . Transfus. Apher. Sci. . 37 . 2 . 131–7 . October 2007 . 17950672 . 10.1016/j.transci.2007.07.002 .
10. CaridianBCT. (2010, June 23). CaridianBCT’s Mirasol Pathogen Reduction Technologies System Selected to Increase Safety of Poland’s Blood Supply. [Press Release]. Retrieved from http://www.caridianbct.com/location/north-america/about-caridianbct/press-room/Pages/23JUN,2010-CaridianBCTMirasolPathogenReductionTechnologiesSystemSelectedtoIncreaseSafetyofPoland%E2%80%99sBloodSupply.aspx
11. Business Wire. (2010, July 20). Belgian Red Cross-Flanders Selects CaridianBCT’s Mirasol® Pathogen Reduction Technology System. [Press Release]. Retrieved from http://www.businesswire.com/news/home/20100720007038/en/Belgian-Red-Cross-Flanders-Selects-CaridianBCT%E2%80%99s-Mirasol%C2%AE-Pathogen
12. All Business. (2008, October 6). Warsaw Blood Center Selects CaridianBCT for Mirasol PRT. [Press Release]. Retrieved from http://www.allbusiness.com/medicine-health/public-health-blood-supply-donations/11595632-1.html
13. Healthcare Technology Online. (2008, August 6). CaridianBCT Receives CE Mark for Mirasol Pathogen Reduction Technology System for Plasma. [Press Release]. Retrieved from http://www.healthcaretechnologyonline.com/article.mvc/CaridianBCT-Receives-CE-Mark-For-Mirasol-0001?VNETCOOKIE=NO