Pathogen Inactivation Technologies for Cellular Blood Components: an Update

Abstract

Nowadays patients receiving blood components are exposed to much less transfusion-transmitted infectious diseases than three decades before when among others HIV was identified as causative agent for the acquired immunodeficiency syndrome and the transmission by blood or coagulation factors became evident. Since that time the implementation of measures for risk prevention and safety precaution was socially and politically accepted. Currently emerging pathogens like arboviruses and the well-known bacterial contamination of platelet concentrates still remain major concerns of blood safety with important clinical consequences, but very rarely with fatal outcome for the blood recipient. In contrast to the well-established pathogen inactivation strategies for fresh frozen plasma using the solvent-detergent procedure or methylene blue and visible light, the bench-to-bedside translation of novel pathogen inactivation technologies for cell-containing blood components such as platelets and red blood cells are still underway. This review summarizes the pharmacological/toxicological assessment and the inactivation efficacy against viruses, bacteria, and protozoa of each of the currently available pathogen inactivation technologies and highlights the impact of the results obtained from several randomized clinical trials and hemovigilance data. Until now in some European countries pathogen inactivation technologies are in in routine use for single-donor plasma and platelets. The invention and adaption of pathogen inactivation technologies for red blood cell units and whole blood donations suggest the universal applicability of these technologies and foster a paradigm shift in the manufacturing of safe blood.

Humanes Cytomegalievirus (HCMV)

“…Neue Studienergebnisse belegen, dass frisch serokonvertierte Spender die höchsten Viruskonzentrationen im Verlauf einer HCMV-Infektion haben. Diese Spender waren klinisch asymptomatisch und wurden ohne HCMV-Diagnostik nicht erkannt [9, [152][153][154][155][156][157][158].…”

“…Jedoch sollte längerfris-tig die Anwendung solcher Präparate wissenschaftlich begleitet werden [150,160]. Verfahren zur Inaktivierung von Pathogenen in Erythrozytenpräparaten sind noch in Entwicklung und müssen in klinischen Studien weiter untersucht werden [155,158].…”

Pathogen Inactivation Plays an Irreplaceable Role in Safeguarding the Safety of Blood Transfusion

“…Through a three-step of intercalation, monoadduct and cross-links (diadducts) chemical reactions between single-or double-stranded DNA or RNA, UVA-light-mediated amotosalen inhibits nucleic acids replication, transcription and repair mechanisms as well. Due to hemoglobin absorbs the UVA light, Amotosalen/UVA based PI cannot be used for inactivation of RBCs [9,11]. Intercept® plasma (Cerus, Concord, CA), as a successfully developed commercial product of Amotosalen/UVA, has been used for nearly a decade in more than 20 countries.…”

“…This technology has been proved to be effective to inactivate a broad spectrum of viruses, bacteria and parasites as well as leukocytes contained in the blood products and considered to be safe without any unusual adverse effects or toxicity events. It has received CE Class III mark approval in Europe and approval for use in the USA in 2006 and 2014, respectively [11,12].…”

“…Mirasol® (Terumo BCT, USA), based on Riboflavin/UVB PI technology, has been used in a number of blood centers in many countries and received CE Class II b mark approval for platelets inactivation in October 2007 and plasma in August 2008. As for the Theraflex UV-Platelets system, it cannot be used routinely because further clinical evaluation is needed [11,13].…”