UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Pathogen inactivation of blood products

Author
Arthur J Silvergleid, MD
Section Editor
Steven Kleinman, MD
Deputy Editor
Jennifer S Tirnauer, MD

INTRODUCTION

The possibility of transmitting infectious organisms via blood products and plasma derivatives is a major public health concern. The paradigm for ensuring the safety of the blood supply using donor screening and laboratory testing is limited because it requires prior knowledge of the possible infectious agents, development of effective laboratory tests for each agent, and widespread application of that testing to all collected blood. For this reason, it has been a long-sought goal to find an effective way to sterilize blood after collection using a pathogen inactivation technology.

This topic review discusses available methods for pathogen inactivation of blood products including plasma, platelets, red blood cells, and plasma derivatives, and it provides evidence for the effectiveness and potential limitations of these procedures.

Approaches to reducing infectious risk using blood donor screening and blood product testing to eliminate products at risk of carrying infectious organisms are discussed in separate topic reviews. (See "Blood donor screening: Medical history" and "Blood donor screening: Laboratory testing" and "Blood donor screening: Procedures and processes to enhance safety for the blood recipient and the blood donor".)

GENERAL PRINCIPLES OF PATHOGEN INACTIVATION

Terminology — The terms pathogen inactivation and pathogen reduction have been used interchangeably by some authors. Strictly speaking, pathogen inactivation refers to complete prevention of infectivity by a pathogen, whereas pathogen reduction refers to decreasing the amount of an infectious pathogen, either by physical removal (eg, nanofiltration) or by an inactivation technique. Some experts have proposed that the term "pathogen inactivation" be used to refer to the processing of the component, and "pathogen-reduced blood component" be used to refer to the transfusable product because no method can guarantee complete sterility of the component [1].

Potential benefits — In principle, pathogen inactivation technologies have the potential to make the blood supply safer by broadly eliminating infectious organisms without the need to screen or test for specific pathogens. This is especially appealing for pathogens that cause asymptomatic infection (and thus would not be identified by donor screening), those with a long window period during which serologic testing would be ineffective, and emerging infectious diseases such as dengue virus, chikungunya virus, Zika virus, Babesia, and as yet unknown emerging pathogens for which donated blood is not screened.

              

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Mar 2016. | This topic last updated: Apr 18, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Lozano M, Cid J, Prowse C, et al. Pathogen inactivation or pathogen reduction: proposal for standardization of nomenclature. Transfusion 2015; 55:690.
  2. Pamphilon D. Viral inactivation of fresh frozen plasma. Br J Haematol 2000; 109:680.
  3. Schimpf K, Mannucci PM, Kreutz W, et al. Absence of hepatitis after treatment with a pasteurized factor VIII concentrate in patients with hemophilia and no previous transfusions. N Engl J Med 1987; 316:918.
  4. Lawrence JE. Affinity chromatography to remove viruses during preparation of plasma derivatives. In: Virological Safety of Plasma Derivatives, Brown F (Ed), Karger, Basel 1993. p.191.
  5. Horowitz MS, Rooks C, Horowitz B, Hilgartner MW. Virus safety of solvent/detergent-treated antihaemophilic factor concentrate. Lancet 1988; 2:186.
  6. Snyder EL, Dodd RY. Reducing the risk of blood transfusion. Hematology Am Soc Hematol Educ Program 2001; :433.
  7. Tabor E. The epidemiology of virus transmission by plasma derivatives: clinical studies verifying the lack of transmission of hepatitis B and C viruses and HIV type 1. Transfusion 1999; 39:1160.
  8. Horowitz B, Busch M. Estimating the pathogen safety of manufactured human plasma products: application to fibrin sealants and to thrombin. Transfusion 2008; 48:1739.
  9. Dichtelmüller HO, Biesert L, Fabbrizzi F, et al. Robustness of solvent/detergent treatment of plasma derivatives: a data collection from Plasma Protein Therapeutics Association member companies. Transfusion 2009; 49:1931.
  10. Hellstern P, Solheim BG. The Use of Solvent/Detergent Treatment in Pathogen Reduction of Plasma. Transfus Med Hemother 2011; 38:65.
  11. Pehta JC. Clinical studies with solvent detergent-treated products. Transfus Med Rev 1996; 10:303.
  12. Lerner RG, Nelson J, Sorcia E, et al. Evaluation of solvent/detergent-treated plasma in patients with a prolonged prothrombin time. Vox Sang 2000; 79:161.
  13. Lambrecht B, Mohr H, Knüver-Hopf J, Schmitt H. Photoinactivation of viruses in human fresh plasma by phenothiazine dyes in combination with visible light. Vox Sang 1991; 60:207.
  14. Zeiler T, Riess H, Wittmann G, et al. The effect of methylene blue phototreatment on plasma proteins and in vitro coagulation capability of single-donor fresh-frozen plasma. Transfusion 1994; 34:685.
  15. Atance R, Pereira A, Ramírez B. Transfusing methylene blue-photoinactivated plasma instead of FFP is associated with an increased demand for plasma and cryoprecipitate. Transfusion 2001; 41:1548.
  16. Suontaka AM, Blombäck M, Chapman J. Changes in functional activities of plasma fibrinogen after treatment with methylene blue and red light. Transfusion 2003; 43:568.
  17. Moog R, Reichenberg S, Hoburg A, Müller N. Quality of methylene-blue-treated fresh-frozen plasma stored up to 27 months. Transfusion 2010; 50:516.
  18. http://www.interceptbloodsystem.com/product-overview/amotosalen-mechanism-of-action.
  19. Singh Y, Sawyer LS, Pinkoski LS, et al. Photochemical treatment of plasma with amotosalen and long-wavelength ultraviolet light inactivates pathogens while retaining coagulation function. Transfusion 2006; 46:1168.
  20. Schlenke P, Hervig T, Isola H, et al. Photochemical treatment of plasma with amotosalen and UVA light: process validation in three European blood centers. Transfusion 2008; 48:697.
  21. Hambleton J, Wages D, Radu-Radulescu L, et al. Pharmacokinetic study of FFP photochemically treated with amotosalen (S-59) and UV light compared to FFP in healthy volunteers anticoagulated with warfarin. Transfusion 2002; 42:1302.
  22. Ciaravino V. Preclinical safety of a nucleic acid-targeted Helinx compound: a clinical perspective. Semin Hematol 2001; 38:12.
  23. de Alarcon P, Benjamin R, Dugdale M, et al. Fresh frozen plasma prepared with amotosalen HCl (S-59) photochemical pathogen inactivation: transfusion of patients with congenital coagulation factor deficiencies. Transfusion 2005; 45:1362.
  24. Corbin F 3rd. Pathogen inactivation of blood components: current status and introduction of an approach using riboflavin as a photosensitizer. Int J Hematol 2002; 76 Suppl 2:253.
  25. Marschner S, Goodrich R. Pathogen Reduction Technology Treatment of Platelets, Plasma and Whole Blood Using Riboflavin and UV Light. Transfus Med Hemother 2011; 38:8.
  26. Seghatchian J, Tolksdorf F. Characteristics of the THERAFLEX UV-Platelets pathogen inactivation system - an update. Transfus Apher Sci 2012; 46:221.
  27. Prowse C. Properties of pathogen-inactivated plasma components. Transfus Med Rev 2009; 23:124.
  28. Prowse CV. Component pathogen inactivation: a critical review. Vox Sang 2013; 104:183.
  29. Corash L, Lin L. Novel processes for inactivation of leukocytes to prevent transfusion-associated graft-versus-host disease. Bone Marrow Transplant 2004; 33:1.
  30. Marschner S, Fast LD, Baldwin WM 3rd, et al. White blood cell inactivation after treatment with riboflavin and ultraviolet light. Transfusion 2010; 50:2489.
  31. Brown KE, Young NS, Alving BM, Barbosa LH. Parvovirus B19: implications for transfusion medicine. Summary of a workshop. Transfusion 2001; 41:130.
  32. Schneider B, Becker M, Brackmann HH, Eis-Hübinger AM. Contamination of coagulation factor concentrates with human parvovirus B19 genotype 1 and 2. Thromb Haemost 2004; 92:838.
  33. Klein HG, Dodd RY, Dzik WH, et al. Current status of solvent/detergent-treated frozen plasma. Transfusion 1998; 38:102.
  34. Ludlam CA, Powderly WG, Bozzette S, et al. Clinical perspectives of emerging pathogens in bleeding disorders. Lancet 2006; 367:252.
  35. Flamholz R, Jeon HR, Baron JM, Baron BW. Study of three patients with thrombotic thrombocytopenic purpura exchanged with solvent/detergent-treated plasma: is its decreased protein S activity clinically related to their development of deep venous thromboses? J Clin Apher 2000; 15:169.
  36. Mast AE, Stadanlick JE, Lockett JM, Dietzen DJ. Solvent/detergent-treated plasma has decreased antitrypsin activity and absent antiplasmin activity. Blood 1999; 94:3922.
  37. Nifong TP, Light J, Wenk RE. Coagulant stability and sterility of thawed S/D-treated plasma. Transfusion 2002; 42:1581.
  38. Williamson LM, Llewelyn CA, Fisher NC, et al. A randomized trial of solvent/detergent-treated and standard fresh-frozen plasma in the coagulopathy of liver disease and liver transplantation. Transfusion 1999; 39:1227.
  39. Zeiler T, Wittmann G, Zimmermann R, et al. The effect of virus inactivation on coagulation factors in therapeutic plasma. Br J Haematol 2000; 111:986.
  40. Haubelt H, Blome M, Kiessling AH, et al. Effects of solvent/detergent-treated plasma and fresh-frozen plasma on haemostasis and fibrinolysis in complex coagulopathy following open-heart surgery. Vox Sang 2002; 82:9.
  41. Freeman JW, Williamson LM, Llewelyn C, et al. A randomized trial of solvent/detergent and standard fresh frozen plasma in the treatment of the coagulopathy seen during Orthotopic Liver Transplantation. Vox Sang 1998; 74 Suppl 1:225.
  42. Unger U, Poelsler G, Modrof J, Kreil TR. Virus inactivation during the freeze-drying processes as used for the manufacture of plasma-derived medicinal products. Transfusion 2009; 49:1924.
  43. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427111.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery.
  44. Wagner SJ. Virus inactivation in blood components by photoactive phenothiazine dyes. Transfus Med Rev 2002; 16:61.
  45. Wainwright M, Mohr H, Walker WH. Phenothiazinium derivatives for pathogen inactivation in blood products. J Photochem Photobiol B 2007; 86:45.
  46. Lin L, Cook DN, Wiesehahn GP, et al. Photochemical inactivation of viruses and bacteria in platelet concentrates by use of a novel psoralen and long-wavelength ultraviolet light. Transfusion 1997; 37:423.
  47. Wollowitz S. Fundamentals of the psoralen-based Helinx technology for inactivation of infectious pathogens and leukocytes in platelets and plasma. Semin Hematol 2001; 38:4.
  48. Ljungman P. Risk of cytomegalovirus transmission by blood products to immunocompromised patients and means for reduction. Br J Haematol 2004; 125:107.
  49. Mintz PD, Bass NM, Petz LD, et al. Photochemically treated fresh frozen plasma for transfusion of patients with acquired coagulopathy of liver disease. Blood 2006; 107:3753.
  50. http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/UCM336161.pdf.
  51. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427500.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Accessed on December 19, 2014).
  52. Mirasol Clinical Evaluation Study Group. A randomized controlled clinical trial evaluating the performance and safety of platelets treated with MIRASOL pathogen reduction technology. Transfusion 2010; 50:2362.
  53. Osselaer JC, Doyen C, Defoin L, et al. Universal adoption of pathogen inactivation of platelet components: impact on platelet and red blood cell component use. Transfusion 2009; 49:1412.
  54. Osselaer JC, Messe N, Hervig T, et al. A prospective observational cohort safety study of 5106 platelet transfusions with components prepared with photochemical pathogen inactivation treatment. Transfusion 2008; 48:1061.
  55. Schlenke P, Hagenah W, Irsch J, et al. Safety and clinical efficacy of platelet components prepared with pathogen inactivation in routine use for thrombocytopenic patients. Ann Hematol 2011; 90:1457.
  56. Cazenave JP, Isola H, Waller C, et al. Use of additive solutions and pathogen inactivation treatment of platelet components in a regional blood center: impact on patient outcomes and component utilization during a 3-year period. Transfusion 2011; 51:622.
  57. Vamvakas EC. Meta-analysis of the studies of bleeding complications of platelets pathogen-reduced with the Intercept system. Vox Sang 2012; 102:302.
  58. Butler C, Doree C, Estcourt LJ, et al. Pathogen-reduced platelets for the prevention of bleeding. Cochrane Database Syst Rev 2013; 3:CD009072.
  59. Cancelas JA, Dumont LJ, Rugg N, et al. Stored red blood cell viability is maintained after treatment with a second-generation S-303 pathogen inactivation process. Transfusion 2011; 51:2367.
  60. https://clinicaltrials.gov/ct2/show/NCT02118428 (Accessed on March 09, 2016).