Pathogen reduction using riboflavin and UV light

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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.

Contents

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

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).

Related Research Articles

<span class="mw-page-title-main">Blood type</span> Classification of blood based on antibodies and antigens on red blood cell surfaces

A blood type is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system. Some of these antigens are also present on the surface of other types of cells of various tissues. Several of these red blood cell surface antigens can stem from one allele and collectively form a blood group system.

<span class="mw-page-title-main">Blood transfusion</span> Intravenous transference of blood products

Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but modern medical practice commonly uses only components of the blood, such as red blood cells, plasma, platelets, and other clotting factors. White blood cells are transfused only in very rare circumstances, since granulocyte transfusion has limited applications. Whole blood has come back into use in the setting of trauma.

<span class="mw-page-title-main">Platelet</span> Component of blood aiding in coagulation

Platelets or thrombocytes are a blood component whose function is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm derived from the megakaryocytes of the bone marrow or lung, which then enter the circulation. Platelets are found only in mammals, whereas in other vertebrates, thrombocytes circulate as intact mononuclear cells.

<span class="mw-page-title-main">Whole blood</span> Unseparated donated human blood

Whole blood (WB) is human blood from a standard blood donation. It is used in the treatment of massive bleeding, in exchange transfusion, and when people donate blood to themselves. One unit of whole blood brings up hemoglobin levels by about 10 g/L. Cross matching is typically done before the blood is given. It is given by injection into a vein.

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<span class="mw-page-title-main">Blood bank</span> Place where blood donations are collected

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<span class="mw-page-title-main">Blood donation</span> Blood withdrawal for use by another person via transfusion

A blood donation occurs when a person voluntarily has blood drawn and used for transfusions and/or made into biopharmaceutical medications by a process called fractionation. Donation may be of whole blood, or of specific components directly (apheresis). Blood banks often participate in the collection process as well as the procedures that follow it.

<span class="mw-page-title-main">Apheresis</span> Medical techniques to separate one or more components of blood

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<span class="mw-page-title-main">Plateletpheresis</span> Method of collecting platelets from blood

Plateletpheresis is the process of collecting thrombocytes, more commonly called platelets, a component of blood involved in blood clotting. The term specifically refers to the method of collecting the platelets, which is performed by a device used in blood donation that separates the platelets and returns other portions of the blood to the donor. Platelet transfusion can be a life-saving procedure in preventing or treating serious complications from bleeding and hemorrhage in patients who have disorders manifesting as thrombocytopenia or platelet dysfunction. This process may also be used therapeutically to treat disorders resulting in extraordinarily high platelet counts such as essential thrombocytosis.

Leukoreduction is the removal of white blood cells from the blood or blood components supplied for blood transfusion. After the removal of the leukocytes, the blood product is said to be leukoreduced.

<span class="mw-page-title-main">Psoralen</span> Chemical compound

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<span class="mw-page-title-main">Platelet transfusion</span> Treatment for bleeding irregularities

Platelet transfusion, also known as platelet concentrate, is used to prevent or treat bleeding in people with either a low platelet count or poor platelet function. Often this occurs in people receiving cancer chemotherapy. Preventive transfusion is often done in those with platelet levels of less than 10 x 109/L. In those who are bleeding transfusion is usually carried out at less than 50 x 109/L. Blood group matching (ABO, RhD) is typically recommended before platelets are given. Unmatched platelets, however, are often used due to the unavailability of matched platelets. They are given by injection into a vein.

<span class="mw-page-title-main">Ultraviolet germicidal irradiation</span> Disinfection method using ultraviolet light

Ultraviolet germicidal irradiation (UVGI) is a disinfection technique employing ultraviolet (UV) light, particularly UV-C (180–280 nm), to kill or inactivate microorganisms. UVGI primarily inactivates microbes by damaging their genetic material, thereby inhibiting their capacity to carry out vital functions.

Viral inactivation is to stop the viruses in a given sample from contaminating the desired product either by removing viruses completely or rendering them non-infectious. These techniques are used widely in the food and blood plasma industries, as those products can be harmed by the presence of viral particles. Some of the more common viruses removed by these methods are the HIV-1 and HIV-2 viruses; hepatitis A, B, and C; and parvoviruses. These methods have been adapted to remove prions, which are not related to viruses, from blood products.

Platelet transfusion refractoriness is the repeated failure to achieve the desired level of blood platelets in a patient following a platelet transfusion. The cause of refractoriness may be either immune or non-immune. Among immune-related refractoriness, antibodies against HLA antigens are the primary cause. Non-immune causes include splenomegaly, fever, and sepsis.

Febrile non-hemolytic transfusion reaction (FNHTR) is the most common type of transfusion reaction. It is a benign occurrence with symptoms that include fever but not directly related with hemolysis. It is caused by cytokine release from leukocytes within the donor product as a consequence of white blood cell breakdown .These inflammatory mediators accumulate during the storage of the donated blood, and so the frequency of this reaction increases with the storage length of donated blood. This is in contrast to transfusion-associated acute lung injury, in which the donor plasma has antibodies directed against the recipient HLA antigens, mediating the characteristic lung damage.

Platelet swirling is a noninvasive method for testing the quality of platelet-rich plasma (PRP). Platelet swirling is caused by light diffraction due to the alignment of normal disc-shaped platelets. These discs align light that is diffracted, creating a cloud- or swirl-like appearance.

Plasma frozen within 24 hours after phlebotomy, commonly called FP24, PF‑24, or similar names, is a frozen human blood plasma product used in transfusion medicine. It differs from fresh-frozen plasma (FFP) in that it is frozen within 24 hours of blood collection, whereas FFP is frozen within 8 hours. The phrase "FFP" is sometimes used to refer to any frozen blood plasma product intended for transfusion.

An allergic transfusion reaction is when a blood transfusion results in allergic reaction. It is among the most common transfusion reactions to occur. Reported rates depend on the degree of active surveillance versus passing reporting to the blood bank. Overall, they are estimated to complicate up to 3% of all transfusions. The incidence of allergic transfusion reactions is associated with the amount of plasma in the product. More than 90% of these reactions occur during transfusion.

Cerus Corporation is an American multinational biotechnology company headquartered in Concord, California that develops and provides a treatment system to pathogen-reduce human blood products for the healthcare industry.

References

  1. 1 2 3 Hardwick CC, Herivel TR, Hernandez SC, Ruane PH, Goodrich RP (2004). "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. doi:10.1562/0031-8655(2004)080<0609:TNSIAQ>2.0.CO;2. ISSN   0031-8655. PMID   15382964. S2CID   198154059.
  2. 1 2 Sullivan J, et al. (2008). "Pathogen Inactivation of plasmodium Falciparum in Plasma and Platelet Concentrations with Riboflavin and UV Light". Vox Sanguinis. 95 (Suppl. 1): 278–279. doi:10.1111/j.1423-0410.2008.01056.x. hdl: 10292/2147 .
  3. ↑ Reddy HL, Dayan AD, Cavagnaro J, Gad S, Li J, Goodrich RP (April 2008). "Toxicity testing of a novel riboflavin-based technology for pathogen reduction and white blood cell inactivation". Transfus Med Rev. 22 (2): 133–53. doi:10.1016/j.tmrv.2007.12.003. PMID   18353253.
  4. ↑ Larrea L, Calabuig M, Roldán V, Rivera J, Tsai HM, Vicente V, Roig R (December 2009). "The influence of riboflavin photochemistry on plasma coagulation factors". Transfus. Apher. Sci. 41 (3): 199–204. doi:10.1016/j.transci.2009.09.006. PMC   3158998 . PMID   19782644.
  5. 1 2 3 Ruane PH, Edrich R, Gampp D, Keil SD, Leonard RL, Goodrich RP (June 2004). "Photochemical inactivation of selected viruses and bacteria in platelet concentrates using riboflavin and light". Transfusion. 44 (6): 877–85. doi:10.1111/j.1537-2995.2004.03355.x. PMID   15157255. S2CID   24109912.
  6. ↑ Goodrich RP, et al. (2006). "Chapter 5:The Antiviral and Antibacterial Properties of Riboflavin and Light: Applications to Blood Safety and Transfusion Medicine". In Edwards, Ana M., Silva, Eduardo (eds.). Flavins: photochemistry and photobiology. Cambridge: RSC Publishing. ISBN   0-85404-331-4.
  7. 1 2 Fast LD, Dileone G, Marschner S (December 2010). "Inactivation of human white blood cells in platelet products after pathogen reduction technology treatment in comparison to gamma irradiation". Transfusion. 51 (7): 1397–1404. doi:10.1111/j.1537-2995.2010.02984.x. PMID   21155832. S2CID   34154946.
  8. ↑ Goodrich RP, Custer B, Keil S, Busch M (August 2010). "Defining "adequate" pathogen reduction performance for transfused blood components". Transfusion. 50 (8): 1827–37. doi:10.1111/j.1537-2995.2010.02635.x. PMID   20374558. S2CID   11538115.
  9. ↑ Cardo LJ, Salata J, Mendez J, Reddy H, Goodrich R (October 2007). "Pathogen inactivation of Trypanosoma cruzi in plasma and platelet concentrates using riboflavin and ultraviolet light". Transfus. Apher. Sci. 37 (2): 131–7. doi:10.1016/j.transci.2007.07.002. PMID   17950672.
  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
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