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Background: Ebola virus (EBOV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have been identified as potential threats to blood safety. This study investigated the efficacy of the THERAFLEX UV-Platelets and THERAFLEX MB-Plasma pathogen inactivation systems to inactivate EBOV and MERS-CoV in platelet concentrates (PCs) and plasma, respectively., Study Design and Methods: PCs and plasma were spiked with high titers of cell culture-derived EBOV and MERS-CoV, treated with various light doses of ultraviolet C (UVC; THERAFLEX UV-Platelets) or methylene blue (MB) plus visible light (MB/light; THERAFLEX MB-Plasma), and assessed for residual viral infectivity., Results: UVC reduced EBOV (≥4.5 log) and MERS-CoV (≥3.7 log) infectivity in PCs to the limit of detection, and MB/light decreased EBOV (≥4.6 log) and MERS-CoV (≥3.3 log) titers in plasma to nondetectable levels., Conclusions: Both THERAFLEX UV-Platelets (UVC) and THERAFLEX MB-Plasma (MB/light) effectively reduce EBOV and MERS-CoV infectivity in platelets and plasma, respectively., (© 2018 AABB.)

Background: Platelet additive solutions (PASs) facilitate plasma recovery and may reduce the risk of plasma-associated adverse transfusion reactions. Whereas current apheresis techniques are able to produce platelet concentrates (PCs) with reduced residual plasma volumes, it is still technically challenging to prepare PCs with plasma levels less than 20% from whole blood. This study aimed to evaluate the feasibility of producing buffy coat (BC)-derived platelets (PLTs) with as little as 10% residual plasma and to test the ability of PASs to preserve PLT quality under these conditions., Study Design and Methods: A pool-and-split design was used to evaluate the in vitro quality of semiautomatically prepared BC-derived PCs stored for 7 days in either SSP+ (PAS-IIIM) or Intersol-G (glucose-containing PAS) with 10% to 30% residual plasma in three phases: 1) 30% plasma (SSP+, Intersol-G), 2) 20 and 15% plasma (SSP+, Intersol-G), and 3) 10% plasma (Intersol-G)., Results: The different plasma-reduced PAS-PC types were comparable in volume, PLT concentration, and PLT yield and met all regulatory requirements. The in vitro quality variables of PLTs suspended in 20% or less residual plasma were comparable to those of PLTs stored in 30% plasma for both PAS types. PLT activation was slightly higher with SSP+ than with Intersol-G. The quality of PCs suspended in Intersol-G with 10% plasma was well maintained during storage., Conclusions: Preparation of BC-derived PCs with minimal plasma concentrations as low as 10% is feasible. Late-generation PASs satisfactorily preserve the in vitro quality of such PCs during storage., (© 2015 AABB.)

Methylene blue (MB) was the first method developed for pathogen inactivation of a labile blood component that was introduced in 1991. MB and light (MBL) inactivates most lipid-enveloped viruses and those non-enveloped are, in general, resistant. MBL treatment affects several coagulation factors, most noticeably fibrinogen and factor VIII with a loss of approximately 30%. Using endogenous thrombin potential, a global hemostasis evaluation, MBL treatment of plasma resulted in a 7% to 10% of reduction in thrombin potential. Although, originally, the scientific evidence of its efficacy and safety were scarce, the 4.4 million of units transfused have provided a wide body of evidence of its efficacy and safety in most of clinical situations. Nevertheless, some doubts have arisen about the efficacy of MBL plasma when used as a replacement solution for plasma exchange in the treatment of patients suffering from TTP. Probably only randomized controlled trials would provide definite evidence to clarify this point. Reports of severe allergic reactions in a few patients receiving MBL plasma have provoked the recent decision to remove the product from the market in France. Interestingly hemovigilance data in countries such as the same France, Spain, and United Kingdom have not corroborated an increase in severe allergic reaction. Close monitoring of the patients receiving plasma and suffering from allergic reactions and reporting to hemovigilance schemes hopefully will provide the needed data to definitely establish the exact risk of this complication for MBL vs other types of plasma., (© 2013.)

The use of pathogen reduction technologies (PRTs) for labile blood components is slowly but steadily increasing. While pathogen-reduced plasma is already used routinely, efficacy and safety concerns impede the widespread use of pathogen-reduced platelets. The supportive and often prophylactic nature of blood component therapy in a variety of clinical situations complicates the clinical evaluation of these novel blood products. However, an increasing body of evidence on the clinical efficacy, safety, cost-benefit ratio and development of novel technologies suggests that pathogen reduction has entered a stage of maturity that could further increase the safety margin in haemotherapy. This review summarizes the clinical evidence on PRTs for plasma and platelet products that are currently licensed or under development., (© 2013 John Wiley & Sons Ltd.)

Background: 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., Study Design and Methods: 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., Results: 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., Conclusions: 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., (© 2012 American Association of Blood Banks.)

Background: Ultraviolet (UV) light, especially UVC, is germicidal but its ability to penetrate layers of protein containing solutions is poor. This hampers its use to inactivate pathogens in therapeutic fresh plasma (FP)., Study Design and Methods: FP units were spiked with lipid-enveloped or nonenveloped viruses. Others were used without spiking. The units were transferred into UV-transparent bags and irradiated with UVB or UVC light from both sides. The bags either were clamped between quartz plates or remained loose. In addition they were agitated at different speeds. Before and after irradiation virus titers or plasma variables were measured., Results: Virus inactivation by UV irradiation was marginal when the FP units were not agitated or when the irradiation bags were fixed between quartz plates. It was strongly enhanced when they remained unfixed and were intensively agitated during treatment. At 100 rpm and UVC doses of approximately 1 J/cm(2), with the exception of human immunodeficiency virus Type 1, all viruses used were effectively inactivated. UVB up to 2.5 J/cm(2) was less effective. At 1 J/cm(2) UVC or 2.5 J/cm(2) UVB the activities of the clotting factors tested in general were reduced by approximately 10% to 20% compared to untreated plasma. More sensitive was clotting factor XI whose activity was lowered by approximately 23 and 29%, respectively. No further reductions were determined after storage of UVC-treated FP for 3 months at 30 degrees C or less., Conclusions: Pathogen inactivation of FP by UV light becomes effective when the unfixed irradiation bags are strongly agitated. The decrease in some clotting factor activities could be acceptable.

Background: A fully automated single-tube assay with tubes (BD TruCOUNT, BD Biosciences) for absolute counting of residual cells in freshly prepared plasma by flow cytometry was developed (BD Plasma Count)., Study Design and Methods: The nucleic acid dye thiazole orange stains white blood cells (WBCs). The monoclonal antibodies anti-CD41a-peridinin chlorophyll protein-Cy5.5 and anti-glycophorin A-fluorescein isothiocyanate label platelets (PLTs) and red blood cells (RBCs), respectively. No fixation, permeabilization, or washing steps were required. Validation was done according to guidelines of the International Conference on Harmonization and the National Committee for Clinical Laboratory Standards. Cell-free plasma was spiked with each cell type for accuracy, reproducibility, and linearity measurements., Results: Results showed no carryover or drift under automated sample acquisition conditions. Nonspecific background was fewer than 0.3 cells per microL for residual WBCs (rWBCs), fewer than 2.7 cells per microL for rRBCs, and fewer than 85 cells per microL for rPLTs. Determinations of rWBC and rPLT counts were linear with a coefficient of variation of less than 12 percent for the imprecision. Owing to cross-linking of the anti-glycophorin A antibody, linearity and precision for rRBCs diverged up to 21 percent at a count of 6000 rRBCs per microL. In a 2-year period, five operators investigated 2666 quality control (QC) samples of fresh-frozen plasma on 108 working days. Maximum cell numbers found were 196 for rWBCs, 3960 for rRBCs, and 28,952 for rPLTs per microL. In 31 cases (1.2%) rWBCs were out of specification. No outlier was observed for rRBCs and rPLTs. Residual RBC cell numbers determined were always within the acceptable concentration range of the assay., Conclusion: These data demonstrate that the single-tube test is suitable for routine QC assessment of the cellular contaminants of therapeutic plasma according to the European recommendations.

Background: The epidemic of West Nile virus (WNV) in the US resulted in cases of transfusion-transmitted WNV. Effective pathogen reduction methods could have removed this infectious agent from the blood supply We have evaluated the efficacy of photodynamic treatment of fresh frozen plasma (FFP) with methylene blue (MB), a decontamination method applied in several European countries., Study Design and Methods: FFP units (300 ml each) were spiked with WNV. MB was added, and the units were illuminated with white or monochromatic yellow light. WNV infectivity was determined by bioassay. WNV-RNA was quantitated by real-time PCR. The inactivation of WNV was investigated under standard and under suboptimal conditions, respectively. In addition, rechallenge experiments with multiple addition of WNV at maximal load (approx. 105 CFU/ml) and repeated illumination without replenishing MB were performed., Results: Complete inactivation of WNV was achieved by MB (0.8-1 mmol/l) and illumination with white light (30,000-45,000 Lux) within 2 min. White yellow light 20-40 J/cm(2) (2.5-5 min) were sufficient for inactivation by 5.75 log10-steps. The rechallenge experiments revealed the substantial reserve capacity of the procedure to inactivate WNV. Quantitative PCR indicated that the viral RNA was rapidly destroyed., Conclusion: All experimental data demonstrate the enormous potency of phototreatment with MB to inactivate WNV in plasma.

Background: Emerging viruses like severe acute respiratory syndrome coronavirus (SARS‐CoV), Crimean–Congo haemorrhagic fever virus (CCHFV) and Nipah virus (NiV) have been identified to pose a potential threat to transfusion safety. In this study, the ability of the THERAFLEX UV‐Platelets and THERAFLEX MB‐Plasma pathogen inactivation systems to inactivate these viruses in platelet concentrates and plasma, respectively, was investigated. Materials and methods: Blood products were spiked with SARS‐CoV, CCHFV or NiV, and then treated with increasing doses of UVC light (THERAFLEX UV‐Platelets) or with methylene blue (MB) plus increasing doses of visible light (MB/light; THERAFLEX MB‐Plasma). Samples were taken before and after treatment with each illumination dose and tested for residual infectivity. Results: Treatment with half to three‐fourths of the full UVC dose (0·2 J/cm2) reduced the infectivity of SARS‐CoV (≥3·4 log), CCHFV (≥2·2 log) and NiV (≥4·3 log) to the limit of detection (LOD) in platelet concentrates, and treatment with MB and a fourth of the full light dose (120 J/cm2) decreased that of SARS‐CoV (≥3·1 log), CCHFV (≥3·2 log) and NiV (≥2·7 log) to the LOD in plasma. Conclusion: Our study demonstrates that both THERAFLEX UV‐Platelets (UVC) and THERAFLEX MB‐Plasma (MB/light) effectively reduce the infectivity of SARS‐CoV, CCHFV and NiV in platelet concentrates and plasma, respectively. [ABSTRACT FROM AUTHOR]

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. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]