Influence of riboflavin and ultraviolet-light treatment on plasma proteins – protein S and alpha 2-antiplasmin – in relation to the time of administration

  • Dragana Gojkov Military Medical Academy, Institute for Transfusiology and Haemobiology, Belgrade, Serbia
  • Bela Balint Serbian Academy of Sciences and Arts, Department of Medical Sciences, Belgrade, Serbia
  • Bratislav Dejanović Military Medical Academy, Institute for Medical Biochemistry, Belgrade, Serbia
  • Dušan Vučetić Military Medical Academy, Institute for Transfusiology and Haemobiology, Belgrade, Serbia
Keywords: alpha-2-antiplasmin, plasma, proteins, protein s, riboflavin, safety, time factors, ultraviolet rays

Abstract


Background/Aim. After the introduction of a careful selection procedure for blood donors and the implementation of highly sensitive screening tests for transfusion-transmitted infections (TTIs), blood has become a very safe product concerning TTIs. However, due to the existence of a “window” period during which these “markers” cannot be detected, as well as the emergence of new pathogens, the risk is still present. Implementation of pathogen reduction technology (PRT) provides a proactive approach to improving blood safety. By damaging nucleic acids, PRT selectively inactivates pathogens and leucocytes. Nevertheless, during the process, plasma proteins are also damaged to some extent. The aim of this study was to conclude whether there is a difference in the effect of  PRT on protein S (PS) and alpha 2-antiplasmin (α2AP) regarding the time of inactivation: inactivation immediately after plasma separation from whole blood (before freezing) vs. inactivation after freezing/thawing. Methods. The voluntary donors’ blood is taken into a quadruple bag system, centrifuged, and separated into blood products. Control group plasma was first inactivated by the Mirasol® PRT system and then frozen. Experimental group plasma was immediately frozen and, after four months, thawed and inactivated. PS and α2AP activity was examined in samples after separation, inactivation, and thawing. Results. Analyzing PS and α2AP activity, no statistically significant difference was found between the initial samples. The trend of protein activity reduction after inactivation and freezing/thawing was present in both groups but without a statistically significant intergroup difference. Conclusion. No statistically significant difference was found between the activity values of PS and α2AP after immediate inactivation, before freezing, and after freezing/thawing, making stored plasma units suitable for safe and efficient inactivation directly before clinical use and according to the patient’s blood type.

References

Harmening D. Modern Blood Banking & Transfusion Practices. 6th ed. Philadelphia: Davis Company; 2012. p. 365‒7.

Fung M. Technical Manual 19th ed. Bethesda: AABB, 2017. p. 518.

Kitchen C, Alving B, Kessler C. Consultative Hemostasis and Thrombosis. Philadelphia, Pennsylvania: Elsevier Science; 2002. p. 183.

Rodak B, Fritsma G, Keohane E. Hematology. St. Louis, Mo: Elsevier Saunders; 2012. p. 643.

McCullough J. Pathogen inactivation: a new paradigm for preventing transfusion-transmitted infections. Am J Clin Pathol 2007; 128(6): 945–55.

Klein HG, Glynn SA, Ness PM, Blajchman MA. NHLBI Working Group on Research Opportunities for the Pathogen Reduction/Inactivation of Blood Components. Research opportunities for pathogen reduction/inactivation of blood components: summary of an NHLBI workshop. Transfusion 2009; 49(6): 1262‒8.

Pelletier JP, Transue S, Snyder EL. Pathogen inactivation techniques. Best Pract Res Clin Haematol 2006; 19(1): 205–42.

Elikaei A, Hosseini SM, Sharifi Z. Inactivation of model viruses and bacteria in human fresh frozen plasma using riboflavin and long wave ultraviolet rays. Iran J Microbiol 2017; 9(1): 50‒4.

Jocic M, Trkuljic M, Jovicic D, Borovcanin N, Balint B. Inactivation efficacy of Mirasol PRT in platelet concentrates using bacteria contamination model. Vojnosanit Pregl 2011; 68(12): 1041–6. (Serbian)

Goodrich RP, Doane S, Reddy HL. Design and development of a method for the reduction of infectious pathogen load and inactivation of white blood cells in whole blood products. Biologicals 2010; 38(1): 20–30.

Cicchetti A, Berrino A, Casini M, Codella P, Facco G, Fiore A, et al. Health Technology Assessment of pathogen reduction technologies applied to plasma for clinical use. Blood Transfus 2016; 14(4): 287‒386.

Stanojkovic Z, Balint B, Antic A, Todorovic M, Ostojic G, Pavlovic M. Clinical efficacy of riboflavin and ultraviolet light inactivated fresh frozen plasma evaluated with INR-quantification. Transfus Apher Sci 2012; 47(1): 33‒7.

Keil SD, Ragan I, Yonemura S, Hartson L, Dart NK, Bowen R. Inactivation of severe acute respiratory syndrome coronavirus 2 in plasma and platelet products using a riboflavin and ultraviolet light-based photochemical treatment. Vox Sang 2020; 115(6): 495‒501.

Yonemura S, Doane S, Keil S, Goodrich R, Pidcoke H, Cardoso M. Improving the safety of whole blood-derived transfusion products with a riboflavin-based pathogen reduction technology. Blood Transfus 2017; 15(4): 357‒64.

Dahlbäck B. Vitamin K-Dependent Protein S: Beyond the Protein C Pathway. Semin Thromb Hemost 2018; 44(2): 176‒84.

Fearon A, Pearcy P, Venkataraman S, Shah P. Protein S Deficiency and Arterial Thromboembolism: A Case Report and Review of the Literature. J Hematol 2019; 8(1): 37‒9.

Carpenter SL, Mathew P. α2 -Antiplasmin and its deficiency: fibrinolysis out of balance. Haemophilia 2008; 14: 1250–4.

Lee KN, Lee CS, Tae WC, Jackson KW, Christiansen VJ, McKee PA. Crosslinking of alpha 2-antiplasmin to fibrin. Ann N Y Acad Sci. 2001; 936: 335‒9.

Balint B, Pavlovic M, Todorovic M, Jevtic M, Ristanovic E, Ignjatovic L. The use of original ex vivo immunoadsorption and "multi-manner" apheresis in ABO/H-mismatched kidney transplants - A phase II clinical study. Transfus Apher Sci 2010; 43(2): 141‒8.

Marschner S, Goodrich R. Pathogen Reduction Technology Treatment of Platelets, Plasma and Whole Blood Using Riboflavin and UV Light. Transfus Med Hemother 2011; 38(1): 8–18.

Alter HJ. Pathogen reduction: a precautionary principle paradigm. Transfus Med Rev 2008; 22(2): 97‒102.

Goodrich RP, Platz MS. The design and development of selective, photoactivated drugs for sterilization of blood products. Drugs Future 1997; 22: 159–71.

Kasai H, Yamaizumi Z, Yamamoto F, Bessho T, Nishimura S, Berger M, et al. Photosensitized formation of 8-hydroxyguanine (7,8-dihydro-8-oxoguanine) in DNA by riboflavin. Nucleic Acids Symp Ser 1992; (27): 181‒2.

Kumar V, Lockerbie O, Keil SD, Ruane PH, Platz MS, Martin CB, et al. Riboflavin and UV-light based pathogen reduction: extent and consequence of DNA damage at the molecular level. Photochem Photobiol 2004; 80: 15‒21.

Rock G. A comparison of methods of pathogen inactivation of FFP. Vox Sang 2011; 100(2): 169–78.

Balint B, Jovicic-Gojkov D, Todorovic-Balint M, Subota V, Pavlovic M, Goodrich R. Plasma constituent integrity in pre-storage vs. post-storage riboflavin and UV-light treatment – A comparative study. Transf Apheres Sci 2013; 49(3): 434‒9.

Smith J, Rock G. Protein quality in Mirasol pathogen reduction technology-treated, apheresis-derived fresh-frozen plasma. Transfusion 2010; 50(4): 926–31.

Hornsey VS, Drummond O, Morrison A, McMillan L, MacGregor IR, Prowse CV. Pathogen reduction of fresh plasma using riboflavin and ultraviolet light: effects on plasma coagulation proteins. Transfusion 2009; 49(10): 2167–72.

Ettinger A, Miklauz MM, Hendrix BK, Bihm DJ, Maldonado-Codina G, Goodrich RP. Quality of proteins in riboflavin and UV light-treated FFP during 1 year of storage at-18°C. Transfus Apher Sci 2012; 46(1): 15–18.

Ettinger A, Miklauz MM, Hendrix BK, Bihm DJ, Maldonado-Codina G, Goodrich RP. Protein stability of previously frozen plasma, riboflavin and UV light-treated, refrozen and stored for up to 2 years at-30°C. Transfus Apher Sci. 2011; 44(1): 25–31

Bihm DJ, Ettinger A, Buytaert-Hoefen KA, Hendrix BK, Maldonado-Codina G, Rock G, at al. Characterization of plasma protein activity in riboflavin and UV light-treated fresh frozen plasma during 2 years of storage at -30°C. Vox Sang 2010; 98(2): 108–15.

Singh Y, Sawyer LS, Pinkoski LS, Dupuis KW, Hsu JC, Lin L, et al. Photochemical treatment of plasma with amotosalen and long-wavelength ultraviolet light inactivates pathogens while retaining coagulation function. Transfusion 2006; 46(7): 1168‒77.

Published
2022/11/01
Section
Original Paper