THERAFLEX UV-Platelets System Research Articles

West Nile and Usutu viruses are efficiently inactivated in platelet concentrates by UVC light using the THERAFLEX UV-Platelets system.

West Nile virus (WNV) and Usutu virus (USUV) are mosquito-borne flaviviruses (Flaviviridae) that originated in Africa, have expanded their geographical range during the last decades and caused documented infections in Europe in the last years. Acute WNV and USUV infections have been detected in asymptomatic blood donors by nucleic acid testing. Thus, inactivation of both viral pathogens before blood transfusion is necessary to ensure blood product safety. This study aimed to investigate the efficacy of the THERAFLEX UV-Platelets system to inactivate WNV and USUV in platelet concentrates (PCs). Plasma-reduced PCs were spiked with the virus suspension. Spiked PC samples were taken after spiking (load and hold sample) and after UVC illumination on the Macotronic UV illumination machine with different light doses (0.05, 0.1, 0.15 and 0.2 (standard) J/cm2). Virus loads of WNV and USUV before and after illumination were measured by titration. Infectivity assays showed that UVC illumination inactivated WNV and USUV in a dose-dependent manner. At a UVC dose of 0.2 J/cm2, the WNV titre was reduced by a log10 factor of 3.59 ± 0.43 for NY99 (lineage 1) and 4.40 ± 0.29 for strain ED-I-33/18 (lineage 2). USUV titres were reduced at the same UVC dose by a log10 factor of 5.20 ± 0.70. Our results demonstrate that the THERAFLEX UV-Platelets procedure is an effective technology to inactivate WNV and USUV in contaminated PCs.

Inactivation of SARS-CoV-2 infectivity in platelet concentrates or plasma following treatment with ultraviolet C light or with methylene blue combined with visible light.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unlikely to be a major transfusion-transmitted pathogen, however, convalescent plasma is a treatment option used in some regions. The risk of transfusion-transmitted infections can be minimised by implementing Pathogen Inactivation (PI), such as THERAFLEX MB-Plasma and THERAFLEX UV-Platelets systems. Here we examined the capability of these PI systems to inactivate SARS-CoV-2. SARS-CoV-2 spiked plasma units were treated using the THERAFLEX MB-Plasma system in the presence of methylene blue (~0.8 μmol/L; visible light doses: 20, 40, 60 and 120 [standard] J/cm2 ). SARS-CoV-2 spiked platelet concentrates (PCs) were treated using the THERAFLEX UV-Platelets system (UVC doses: 0.05, 0.10, 0.15 and 0.20 [standard] J/cm2 ). Samples were taken prior to the first and after each illumination dose and viral infectivity was assessed using an immunoplaque assay. Treatment of spiked plasma with the THERAFLEX MB-Plasma system resulted in an average ≥5.03 log10 reduction in SARS-CoV-2 infectivity at one third (40 J/cm2 ) of the standard visible light dose. For the platelet concentrates (PCs), treatment with the THERAFLEX UV-Platelets system resulted in an average ≥5.18 log10 reduction in SARS-CoV-2 infectivity at the standard UVC dose (0.2 J/cm2 ). SARS-CoV-2 infectivity was reduced in plasma and platelets following treatment with the THERAFLEX MB-Plasma and THERAFLEX UV-Platelets systems, to the limit of detection, respectively. These PI technologies could therefore be an effective option to reduce the risk of transfusion-transmitted emerging pathogens. This article is protected by copyright. All rights reserved.

Inactivation of Japanese encephalitis virus in plasma by methylene blue combined with visible light and in platelet concentrates by ultraviolet C light.

Japanese encephalitis virus-spiked plasma units were treated using the THERAFLEX MB-Plasma system (visible light doses, 20, 40, 60, and 120 [standard] J/cm2) in the presence of methylene blue at approximately 0.8 μmol/L and spiked platelet concentrates (PCs) were treated using the THERAFLEX UV-Platelets system (UVC doses, 0.05, 0.10, 0.15, and 0.20 [standard] J/cm2). Samples were taken before the first and after each illumination dose and tested for infectivity using an immunoplaque assay. Treatment of plasma with the THERAFLEX MB-Plasma system resulted in an average of 6.59 log reduction in JEV infectivity at one-sixth of the standard visible light dose (20 J/cm2). For PCs, treatment with the THERAFLEX UV-Platelet system resulted in an average of 7.02 log reduction in JEV infectivity at the standard UVC dose (0.20 J/cm2). The THERAFLEX MB-Plasma and THERAFLEX UV-Platelets systems effectively inactivated JEV in plasma or PCs, and thus these PI technologies could be an effective option to reduce the risk of JEV transfusion transmission.

Hepatitis E virus is effectively inactivated in platelet concentrates by ultraviolet C light

As previous investigations have shown, THERAFLEX UV-Platelets, a UVC-based pathogen inactivation (PI) system, is effective against non-enveloped transfusion-relevant viruses such as hepatitis A virus (HAV), which are insensitive to most PI treatments for blood products. This study investigated the PI efficacy of THERAFLEX UV-Platelets against HEV in platelet concentrates (PCs). Buffy coat-derived PCs in additive solution were spiked with cell culture-derived HEV and treated with the THERAFLEX UV-Platelets system using various doses of UVC (0·05, 0·10, 0·15 and 0·20 (standard) J/cm2 ). Titres of infectious virus in pre- and post-treatment samples were determined using a large-volume plating assay to improve the detection limit of the virus assay. THERAFLEX UV-Platelets dose-dependently inactivated HEV in PCs. The standard UVC dose inactivated the virus to below the limit of detection, corresponding to a mean log reduction of greater than 3·5. Our study demonstrates that the THERAFLEX UV-Platelets system effectively inactivates HEV in PCs.

Pathogen inactivation method using ultraviolet C light

Since the end of the 1990s pathogen inactivation methods were being gradually implemented into routine work of blood transfusion establishments in many countries with regard to blood components dedicated for clinical use. The developed pathogen inactivation methods were either based on chemical compounds eg. the solvent detergent (SD) inactivation method or on photochemical and photodynamic reactions eg. inactivation methods with methylene blue, amotosalen hydrochloride and riboflavin. Blood components inactivated with any of the above mentioned methods still had traces of chemical compounds although removal steps were added (an exception here is the method with riboflavin). Attempts were therefore undertaken to develop an inactivation method based not on chemical compounds but on specific wavelength irradiation. An example of such inactivation method solely based on properties of short-wave UVC-light (UVC) with no photosensitizing chemicals is the Theraflex UV-Platelets system dedicated to platelet concentrates (PCs). The system uses 254 nm wavelength irradiation which is not absorbed by proteins so conventional toxicity tests are not required. The method is effective for clinically significant both G (+) and G (-) bacteria as well as viruses and protozoa. Clinical trials demonstrated reduced recovery of UVC-irradiated platelets and shorter survival time in the recipient’s organism.

Inactivation of yellow fever virus in plasma after treatment with methylene blue and visible light and in platelet concentrates following treatment with ultraviolet C light.

Yellow fever virus (YFV) is endemic to tropical and subtropical areas in South America and Africa, and is currently a major public health threat in Brazil. Transfusion transmission of the yellow fever vaccine virus has been demonstrated, which is indicative of the potential for viral transfusion transmission. An approach to manage the potential YFV transfusion transmission risk is the use of pathogen inactivation (PI) technology systems, such as THERAFLEX MB-Plasma and THERAFLEX UV-Platelets (Macopharma). We aimed to investigate the efficacy of these PI technology systems to inactivate YFV in plasma or platelet concentrates (PCs). YFV spiked plasma units were treated using THERAFLEX MB-Plasma system (visible light doses: 20, 40, 60, and 120 [standard] J/cm2 ) in the presence of methylene blue (approx. 0.8 μmol/L) and spiked PCs were treated using THERAFLEX UV-Platelets system (ultraviolet C doses: 0.05, 0.10, 0.15, and 0.20 [standard] J/cm2 ). Samples were taken before the first and after each illumination dose and tested for residual virus using a modified plaque assay. YFV infectivity was reduced by an average of 4.77 log or greater in plasma treated with the THERAFLEX MB-Plasma system and by 4.8 log or greater in PCs treated with THERAFLEX UV-Platelets system. Our study suggests the THERAFLEX MB-Plasma and the THERAFLEX UV-Platelets systems can efficiently inactivate YFV in plasma or PCs to a similar degree as that for other arboviruses. Given the reduction levels observed in this study, these PI technology systems could be an effective option for managing YFV transfusion-transmission risk in plasma and PCs.

Bacterial inactivation of platelet concentrates with the THERAFLEX UV-Platelets pathogen inactivation system.

The THERAFLEX UV-Platelets system (Maco Pharma) uses ultraviolet C (UVC) light for pathogen inactivation (PI) of platelet concentrates (PCs) without any additional photoactive compound. The aim of the study was to systematically investigate bacterial inactivation with this system under conditions of intended use. The robustness of the system was evaluated by assessing its capacity to inactivate high concentrations of different bacterial species in accordance with World Health Organization guidelines. The optimal use of the PI system was explored in time-to-treatment experiments by testing its ability to sterilize PCs contaminated with low levels of bacteria on the day of manufacture (target concentration, 100 colony-forming units/unit). The bacteria panel used for spiking experiments in this study included the World Health Organization International Repository Platelet Transfusion Relevant Reference Strains (n = 14), commercially available strains (n = 13), and in-house clinical isolates (n = 2). Mean log reduction factors after UVC treatment ranged from 3.1 to 7.5 and varied between different strains of the same species. All PCs (n = 12/species) spiked with up to 200 colony-forming units/bag remained sterile until the end of storage when UVC treated 6 hours after spiking. UVC treatment 8 hours after spiking resulted in single breakthrough contaminations with the fast-growing species Escherichia coli and Streptococcus pyogenes. The UVC-based THERAFLEX UV-Platelets system efficiently inactivates transfusion-relevant bacterial species in PCs. The comprehensive data from this study may provide a valuable basis for the optimal use of this UVC-based PI system.

The impact of refrigerated storage of UVC pathogen inactivated platelet concentrates on invitro platelet quality parameters.

Refrigeration (cold-storage) of pathogen inactivated (PI) platelet components may increase the shelf-life and safety profile of platelet components, compared to conventional room-temperature (RT) storage. Whilst there is substantial knowledge regarding the impact of these individual treatments on platelets, the combined effect has not been assessed. Using a pool-and-split study design, paired buffy-coat derived platelets in 70% platelet additive solution (SSP+; MacoPharma) were left untreated or PI-treated using the THERAFLEX UV-Platelets System (UVC; MacoPharma). Units from each pair were split and stored at room temperature (20-24°C) or cold-stored (2-6°C) to yield RT, cold, RT-UVC and cold-UVC study groups (n=8 in each group). In vitro quality and function was tested over 9days. Cold-storage of UVC-treated platelets reduced glycolytic metabolism (glucose consumption and lactate production) compared to RT-UVC units. Cold-UVC platelets demonstrated complete abrogation of HSR by day 5, increased externalisation of phosphatidylserine (annexin-V binding) and activation of the GPIIb/IIIa receptor (PAC-1 binding) above the levels observed with the individual treatments. Aggregation responses (ADP and collagen) were enhanced in the cold-UVC platelets compared to both RT groups, but this was primarily mediated by cold-storage. Haemostatic function, as measured using TEG, was similar between the groups. Cold-storage of UVC-treated platelets reduced PI-induced acceleration of glycolytic metabolism. However, combining cold-storage and UVC-treatment resulted in additional phenotypic changes compared to each treatment individually. Further work is required to understand the impact of these changes in clinical efficacy.

Ultraviolet C light efficiently inactivates nonenveloped hepatitis A virus and feline calicivirus in platelet concentrates.

Nonenveloped transfusion-transmissible viruses such as hepatitis A virus (HAV) and hepatitis E virus (HEV) are resistant to many of the common virus inactivation procedures for blood products. This study investigated the pathogen inactivation (PI) efficacy of the THERAFLEX UV-Platelets system against two nonenveloped viruses: HAV and feline calicivirus (FCV), in platelet concentrates (PCs). PCs in additive solution were spiked with high titers of cell culture-derived HAV and FCV, and treated with ultraviolet C at various doses. Pre- and posttreatment samples were taken and the level of viral infectivity determined at each dose. For some samples, large-volume plating was performed to improve the detection limit of the virus assay. THERAFLEX UV-Platelets reduced HAV titers in PCs to the limit of detection, resulting in a virus reduction factor of greater than 4.2 log steps, and reduced FCV infectivity in PCs by 3.0 ± 0.2 log steps. THERAFLEX UV-Platelets effectively inactivates HAV and FCV in platelet units.

Mitochondrial DNA multiplex real-time polymerase chain reaction inhibition assay for quality control of pathogen inactivation by ultraviolet C light in platelet concentrates.

Several ultraviolet (UV) light-based pathogen inactivation (PI) technologies for platelet (PLT) products have been developed or are under development. Upon implementation of PI technologies, quality control measures are required to ensure consistent efficiency of the treatment process. Previous reports showed that amotosalen/UVA and riboflavin/UV-based PI technologies induce modifications of the PLT-derived mitochondrial DNA (mtDNA) that can be detected by polymerase chain reaction (PCR) inhibition assays. In this study, we sought to establish a PCR inhibition assay to document the impact of ultraviolet C (UVC) treatment with the THERAFLEX UV-Platelets system on the mitochondrial genome in PLT concentrates (PCs). A multiplex real-time PCR inhibition assay with simultaneous short-amplicon (143 bp) and long-amplicon (794 bp) amplification was developed to detect mtDNA modifications in PLTs after UVC treatment. Assay performance was tested in UVC-treated and untreated, plasma-reduced pooled PCs, and apheresis PCs and challenged using PCs manufactured for a clinical trial under routine-like conditions. UVC illumination of PLTs resulted in dose-dependent inhibition of mtDNA amplification for the larger amplicon. Amplification of the shorter amplicon was not affected by UVC treatment. Evaluation of 283 blinded apheresis and pooled PLT samples from routine-like PC production resulted in prediction of UVC treatment status with 100% accuracy. The proposed dual-amplicon size real-time mtDNA PCR assay effectively detects nucleic acid damage induced by UVC illumination of PLTs and could be useful as an informative indicator of PI quality of the THERAFLEX UV-Platelets system.

Reduction of Zika virus infectivity in platelet concentrates after treatment with ultraviolet C light and in plasma after treatment with methylene blue and visible light.

Zika virus (ZIKV) has emerged as a potential threat to transfusion safety worldwide. Pathogen inactivation is one approach to manage this risk. In this study, the efficacy of the THERAFLEX UV-Platelets system and THERAFLEX MB-Plasma system to inactivate ZIKV in platelet concentrates (PCs) and plasma was investigated. PCs spiked with ZIKV were treated with the THERAFLEX UV-Platelets system at 0.05, 0.10, 0.15, and 0.20 J/cm2 UVC. Plasma spiked with ZIKV was treated with the THERAFLEX MB-Plasma system at 20, 40, 60, and 120 J/cm2 light at 630 nm with at least 0.8 µmol/L methylene blue (MB). Samples were taken before the first and after each illumination dose and tested for residual virus. For each system the level of viral reduction was determined. Treatment of PCs with THERAFLEX UV-Platelets system resulted in a mean of 5 log reduction in ZIKV infectivity at the standard UVC dose (0.20 J/cm2 ), with dose dependency observed with increasing UVC dose. For plasma treated with MB and visible light, ZIKV infectivity was reduced by a mean of at least 5.68 log, with residual viral infectivity reaching the detection limit of the assay at 40 J/cm2 (one-third the standard dose). Our study demonstrates that the THERAFLEX UV-Platelets system and THERAFLEX MB-Plasma system can reduce ZIKV infectivity in PCs and pooled plasma to the detection limit of the assays used. These findings suggest both systems have the capacity to be an effective option to manage potential ZIKV transfusion transmission risk.

Inactivation of dengue, chikungunya, and Ross River viruses in platelet concentrates after treatment with ultraviolet C light.

Arboviruses, including dengue (DENV 1-4), chikungunya (CHIKV), and Ross River (RRV), are emerging viruses that are a risk for transfusion safety globally. An approach for managing this risk is pathogen inactivation, such as the THERAFLEX UV-Platelets system. We investigated the ability of this system to inactivate the above mentioned arboviruses. DENV 1-4, CHIKV, or RRV were spiked into buffy coat (BC)-derived platelet (PLT) concentrates in additive solution and treated with the THERAFLEX UV-Platelets system at the following doses: 0.05, 0.1, 0.15, and 0.2 J/cm(2) (standard dose). Pre- and posttreatment samples were taken for each dose, and the level of viral infectivity was determined. At the standard ultraviolet C (UVC) dose (0.2 J/cm(2) ), viral inactivation of at least 4.43, 6.34, and 5.13 log or more, was observed for DENV 1-4, CHIKV, and RRV, respectively. A dose dependency in viral inactivation was observed with increasing UVC doses. Our study has shown that DENV, CHIKV, and RRV, spiked into BC-derived PLT concentrates, were inactivated by the THERAFLEX UV-Platelets system to the limit of detection of our assay, suggesting that this system could contribute to the safety of PLT concentrates with respect to these emerging arboviruses.

In vitro Quality of Platelets with Low Plasma Carryover Treated with Ultraviolet C Light for Pathogen Inactivation

Background: The THERAFLEX UV-Platelets system uses shortwave ultraviolet C light (UVC, 254 nm) to inactivate pathogens in platelet components. Plasma carryover influences pathogen inactivation and platelet quality following treatment. The plasma carryover in the standard platelets produced by our institution are below the intended specification (<30%). Methods: A pool and split study was carried out comparing untreated and UVC-treated platelets with <30% plasma carryover (n = 10 pairs). This data was compared to components that met specifications (>30% plasma). The platelets were tested over storage for in vitro quality. Results: Platelet metabolism was accelerated following UVC treatment, as demonstrated by increased glucose consumption and lactate production. UVC treatment caused increased externalization of phosphatidylserine on platelets and microparticles, activation of the GPIIb/IIIa receptor (PAC-1 binding), and reduced hypotonic shock response. Platelet function, as measured with thrombelastogram, was not affected by UVC treatment. Components with <30% plasma were similar to those meeting specification with the exception of enhanced glycolytic metabolism. Conclusion: This in vitro analysis demonstrates that treatment of platelets with <30% plasma carryover with the THERAFLEX UV-Platelets system affects some aspects of platelet metabolism and activation, although in vitro platelet function was not negatively impacted. This study also provides evidence that the treatment specifications of plasma carryover could be extended to below 30%.

Pathogen reduction by ultraviolet C light effectively inactivates human white blood cells in platelet products.

Residual white blood cells (WBCs) in cellular blood components induce a variety of adverse immune events, including nonhemolytic febrile transfusion reactions, alloimmunization to HLA antigens, and transfusion-associated graft-versus-host disease (TA-GVHD). Pathogen reduction (PR) methods such as the ultraviolet C (UVC) light-based THERAFLEX UV-Platelets system were developed to reduce the risk of transfusion-transmitted infection. As UVC light targets nucleic acids, it interferes with the replication of both pathogens and WBCs. This preclinical study aimed to evaluate the ability of UVC light to inactivate contaminating WBCs in platelet concentrates (PCs). The in vitro and in vivo function of WBCs from UVC-treated PCs was compared to that of WBCs from gamma-irradiated and untreated PCs by measuring cell viability, proliferation, cytokine secretion, antigen presentation in vitro, and xenogeneic GVHD responses in a humanized mouse model. UVC light was at least as effective as gamma irradiation in preventing GVHD in the mouse model. It was more effective in suppressing T-cell proliferation (>5-log reduction in the limiting dilution assay), cytokine secretion, and antigen presentation than gamma irradiation. The THERAFLEX UV-Platelets (MacoPharma) PR system can substitute gamma irradiation for TA-GVHD prophylaxis in platelet (PLT) transfusion. Moreover, UVC treatment achieves suppression of antigen presentation and inhibition of cytokine accumulation during storage of PCs, which has potential benefits for transfusion recipients.

The efficacy of the ultraviolet C pathogen inactivation system in the reduction of Babesia divergens in pooled buffy coat platelets

Babesia spp. is an intraerythrocytic parasite that causes human babesiosis and its transmission by transfusion has been extensively demonstrated. The aim of this study was to ascertain the efficacy of an ultraviolet C (UVC)-based pathogen inactivation system in the reduction of Babesia divergens-infected platelet (PLT) concentrates and to determine the parasite's ability to survive in PLT concentrates stored under blood bank conditions. This study was conducted using in vitro cultures of B. divergens. The detection limit of the culture assay was established and, subsequently, 15 buffy coat-derived PLT concentrates (BC-PCs) were inoculated with 10(7) B. divergens-infected red blood cells. Infected BC-PCs were irradiated with 0.2 J/cm(2) UVC light using the THERAFLEX UV-Platelets method (Macopharma). Viability and parasite growth were evaluated before and after inactivation. Culture growth kinetics were monitored by DNA incorporation of [(3) H]thymidine. The ability of B. divergens to survive in PLT concentrates was also analyzed. The limit of detection in cultures was established at 0.1 × 10(-6) % parasites. The THERAFLEX UV-Platelets system inactivated B. divergens to below the limit of detection in 12 of 15 BC-PCs (log reduction, >6.0) and to the limit of detection (log reduction, 5.0) in three of 15. It was also demonstrated that B. divergens remains viable in BC-PCs stored up to 7 days. Since B. divergens can survive in PLT concentrates and given the performance of UVC, this system could be considered as an alternative to prevent B. divergens and other Babesia species from being transmitted through PLT transfusions.

Two pathogen reduction technologies—methylene blue plus light and shortwave ultraviolet light—effectively inactivate hepatitis C virus in blood products

Contamination of blood products with hepatitis C virus (HCV) can cause infections resulting in acute and chronic liver diseases. Pathogen reduction methods such as photodynamic treatment with methylene blue (MB) plus visible light as well as irradiation with shortwave ultraviolet (UVC) light were developed to inactivate viruses and other pathogens in plasma and platelet concentrates (PCs), respectively. So far, their inactivation capacities for HCV have only been tested in inactivation studies using model viruses for HCV. Recently, a HCV infection system for the propagation of infectious HCV in cell culture was developed. Inactivation studies were performed with cell culture-derived HCV and bovine viral diarrhea virus (BVDV), a model for HCV. Plasma units or PCs were spiked with high titers of cell culture-grown viruses. After treatment of the blood units with MB plus light (Theraflex MB-Plasma system, MacoPharma) or UVC (Theraflex UV-Platelets system, MacoPharma), residual viral infectivity was assessed using sensitive cell culture systems. HCV was sensitive to inactivation by both pathogen reduction procedures. HCV in plasma was efficiently inactivated by MB plus light below the detection limit already by 1/12 of the full light dose. HCV in PCs was inactivated by UVC irradiation with a reduction factor of more than 5 log. BVDV was less sensitive to the two pathogen reduction methods. Functional assays with human HCV offer an efficient tool to directly assess the inactivation capacity of pathogen reduction procedures. Pathogen reduction technologies such as MB plus light treatment and UVC irradiation have the potential to significantly reduce transfusion-transmitted HCV infections.

Characteristics of the THERAFLEX UV-Platelets pathogen inactivation system – An update

Considerable progress has been made in the last decade in producing purer, safer, leucocyte and plasma reduced platelet concentrates (PC) with an extended shelf life. The development of different pathogen inactivation technologies (PIT) has made a substantial contribution to this trend. Preceding platelet PIT (INTERCEPT Blood System/Cerus Corporation, Concord, CA, USA; MIRASOL/Caridian BCT, Lakewood, CO, USA) are based on adding a photosensitive compound to PC. The mixture is then activated by UV light in the UVB and/or UVA spectral regions. A novel procedure, THERAFLEX UV-Platelets (MacoPharma, Mouvaux, France), was recently developed that uses short-wave ultraviolet light (UVC), without addition of any photoactive agent. This technology has proven to be highly effective in sterilising bacteria (the major cause of morbidity/mortality after platelet transfusion) as well as inactivating other transfusion transmitted DNA/RNA containing pathogens and residual leucocytes.Any PIT reflects a balance between the efficacy of pathogen inactivation and preservation of platelet quality and function. A broad spectrum of in vitro tests have become available for the assessment of platelet storage lesion (PSL), aiming to better predict clinical outcome and untoward effects of platelet therapy. Recent paired studies on the release of platelet-derived cytokines, as new platelet performance indicators, revealed a parallel increase in both THERAFLEX UV-treated and control PC throughout storage, supporting the notion that the bioavailability of platelet function is not grossly affected by UVC treatment. This is corroborated by some newer technologies for proteomic analysis, showing that the THERAFLEX UV-Platelets system results in limited disruption of integrin-regulating extracellular disulfide bonds and minimal protein alterations when compared to UVB and gamma irradiation. Moreover, standard in vitro parameters reflecting activation, metabolic activity and function of platelets are useful indicators of the overall performance of processing and storage and may be used as surrogate markers of platelet quality in vivo. However, there is some doubt as to what degree each marker alone or in combination reflects the true clinical outcome of transfused platelets. Therefore, an appropriate clinical programme has been initiated. The preclinical evaluation demonstrated tolerability and immunological safety of THERAFLEX UV-Platelets using an animal model. Additionally, the system has successfully completed two autologous Phase I trials on recovery and survival. Preliminary results suggest that the recovery and survival rates are consistent with other pathogen reduced platelet products that are licensed and in use. The method is currently under evaluation for safety and tolerability of UVC-treated platelets in healthy volunteers. Presently the THERAFLEX UV-Platelets system is the simplest and purest PIT easily adaptable to the existing blood bank setting. In the future, extension of the application range of the THERAFLEX UV-Platelets system is expected, in order to make this new technology compatible with a broad spectrum of collection and processing platforms, and with other blood products.

UVC Irradiation for Pathogen Reduction of Platelet Concentrates and Plasma

Besides the current efforts devoted to microbial risk reduction, pathogen inactivation technologies promise reduction of the residual risk of known and emerging infectious agents. A novel pathogen reduction process for platelets, the THERAFLEX UV-Platelets system, has been developed and is under clinical evaluation for its efficacy and safety. In addition, proof of principle has been shown for UVC treatment of plasma units. The pathogen reduction process is based on application of UVC light of a specific wavelength (254 nm) combined with intense agitation of the blood units to ensure a uniform treatment of all blood compartments. Due to the different absorption characteristics of nucleic acids and proteins, UVC irradiation mainly affects the nucleic acid of pathogens and leukocytes while proteins are largely preserved. UVC treatment significantly reduces the infectivity of platelet units contaminated by disease-causing viruses and bacteria. In addition, it inactivates residual white blood cells in the blood components while preserving platelet function and coagulation factors. Since no photoactive compound needs to be added to the blood units, photoreagent-related adverse events are excluded. Because of its simple and rapid procedure without the need to change the established blood component preparation procedures, UVC-based pathogen inactivation could easily be implemented in existing blood banking procedures.