Mirasol Pathogen Reduction Technology Research Articles

The safety of pathogen-reduced platelet transfusions in critically ill term and preterm neonates.

Platelet transfusions carry an important risk of infection transmission. The Mirasol Pathogen Reduction Technology system for platelets uses riboflavin and UV light to introduce irreparable lesions into nucleic acids, thereby inhibiting pathogen replication and inactivating white blood cells. The objective of this study is to evaluate the safety of pathogen-reduced platelet transfusions (PRPTs) in critically ill infants in a neonatal intensive care unit (NICU) in the Caribbean. We conducted a descriptive retrospective study of the use of Mirasol PRPTs in patients admitted to the NICU of the general hospital in Curaçao from February 2016 to April 2023. A total of 208 PRPTs were administered to 46 patients (median [range] transfusions per patient: 3 [1-24]). Three patients were born term, and 43 were born preterm (median [range] gestational age: 27 4/7 weeks [24 6/7-36 6/7]). PRPTs were well-tolerated and no complications occurred, especially no signs of haemolysis nor any signs of new infection within 24 h after transfusion. Twenty-one of 46 patients (46%) died during their admittance. None of the deaths were deemed related to PRPT. Mirasol PRPT appears to be safe for use in critically ill neonates, including extremely preterm neonates.

Pathogen reduction of monkeypox virus in plasma and whole blood using riboflavin and UV light.

Monkeypox virus has recently emerged from endemic foci in Africa and, since October 20, 2022, more than 73,000 human infections have been reported by the CDC from over 100 countries that historically have not reported monkeypox cases. The detection of virus in skin lesions, blood, semen, and saliva of infected patients with monkeypox infections raises the potential for disease transmission via routes that have not been previously documented, including by blood and plasma transfusions. Methods for protecting the blood supply against the threats of newly emerging disease agents exist and include Pathogen Reduction Technologies (PRT) which utilize photochemical treatment processes to inactivate pathogens in blood while preserving the integrity of plasma and cellular components. Such methods have been employed broadly for over 15 years, but effectiveness of these methods under routine use conditions against monkeypox virus has not been reported. Monkeypox virus (strain USA_2003) was used to inoculate plasma and whole blood units that were then treated with riboflavin and UV light (Mirasol Pathogen Reduction Technology System, Terumo BCT, Lakewood, CO). The infectious titers of monkeypox virus in the samples before and after riboflavin + UV treatment were determined by plaque assay on Vero cells. The levels of spiked virus present in whole blood and plasma samples exceeded 103 infectious particles per dose, corresponding to greater than 105 DNA copies per mL. Treatment of whole blood and plasma units under standard operating procedures for the Mirasol PRT System resulted in complete inactivation of infectivity to the limits of detection. This is equivalent to a reduction of ≥ 2.86 +/- 0.73 log10 pfu/mL of infectivity in whole blood and ≥ 3.47 +/-0.19 log10 pfu/mL of infectivity in plasma under standard operating conditions for those products. Based on this data and corresponding studies on infectivity in patients with monkeypox infections, use of Mirasol PRT would be expected to significantly reduce the risk of transfusion transmission of monkeypox.

Effect of mirasol pathogen reduction technology system on immunomodulatory molecules of apheresis platelets

Pathogen inactivation for platelets by riboflavin system (MIRASOL) efficiently reduces transfusion related pathogen transmission. However little is known about its impact on platelets’ immunomodulatory biochemical profile. We aimed was to assess the effects of MIRASOL treatment on platelet quality parameters and immunomodulatory molecules CD62P, RANTES, and CD40L in Single Donor Platelets (SDPs) resuspended in plasma (SDP-P) or T-PAS and additive solution (SDP-A). Twenty nine SDPs (15 SDP-P and 14 SDP-A) were included in the study. Samples were collected before, after MIRASOL treatment and just before transfusion. P-selectin (CD62P), RANTES, and CD40L were tested by ELISA. Platelet products quality assays were also performed. Platelet count/unit decreased after Mirasol treatment by 13 %. The pH of all units decreased over the 5-day storage period but remained above expected limits and the swirling test was positive throughout storage. P-selectin levels were not different between the three different time points in both SDPs-P and SDPs-A while RANTES levels were found to differ statistically significantly at the three different time points in all units and in the SPD-A subgroup. CD40L levels in all SDP products increased slightly during storage but this was not statistically significant. CD62P, RANTES, and CD40L in all time points were elevated in SDPs-A compared to SDPs-P but not at a statistically significant level. In conclusion MIRASOL treatment apart from RANTES increase does not seem to substantially affect platelets associated other cytokines and immunomodulatory molecules namely P-selectin and sCD40L which are implicated in immune transfusion reactions.

Haemostatic profile of riboflavin-treated apheresis platelet concentrates.

The haemostatic activity of platelet concentrates (PCs) treated with pathogen reduction technology (PRT) remains a subject of debate. Our aim was to investigate the effect of Mirasol PRT on the haemostatic properties of PCs stored in plasma. Untreated and Mirasol-treated platelets stored in plasma and derived from ten split double-dose apheresis PCs were evaluated in vitro on days 1, 3 and 5 post collection for functionality, microparticle procoagulation activity (MPA), endogenous thrombin potential (ETP), and haemostatic profile using rotational thromboelastometry (ROTEM). P-selectin expression was significantly higher in Mirasol-treated platelets compared with untreated counterparts on days 3 and 5 (p=0.003 and p=0.002, respectively). Clot strength, as shown by EXTEM maximum clot firmness (MCF), was significantly lower in the Mirasol-treated platelets at all time points (days 1, 3, 5) than in untreated platelets (p=0.009, p<0.001, p<0.001, respectively). There was a considerable increase in MPA over time (p<0.001) and this was significantly higher in the Mirasol-treated platelets on day 5 (p=0.015). A notable acceleration of decrease in ETP values was observed for Mirasol-treated PCs over time (p<0.001), with significant differences between PRT-treated and untreated PCs on days 3 and 5 (p=0.038 and p=0.019, respectively). Clot strength attenuation was significantly associated with pH reduction (p<0.001, Spearman's rho: 0.84), increased microparticle procoagulant activity (p<0.001, Spearman's rho: -0.75), and with decreased ETP (p<0.032, Spearman's rho: 0.41). Increased platelet activation induced by PRT treatment leads to a decrease in in vitro haemostatic capacity as seen by reduced clot strength and thrombin generation capacity over time. The clinical relevance of this needs to be investigated.

The Mirasol Evaluation of Reduction in Infections Trial (MERIT): study protocol for a randomized controlled clinical trial

BackgroundTransfusion-transmitted infections (TTIs) are a global health challenge. One new approach to reduce TTIs is the use of pathogen reduction technology (PRT). In vitro, Mirasol PRT reduces the infectious load in whole blood (WB) by at least 99%. However, there are limited in vivo data on the safety and efficacy of Mirasol PRT. The objective of the Mirasol Evaluation of Reduction in Infections Trial (MERIT) is to investigate whether Mirasol PRT of WB can prevent seven targeted TTIs (malaria, bacteria, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, hepatitis E virus, and human herpesvirus 8).MethodsMERIT is a randomized, double-blinded, controlled clinical trial. Recruitment started in November 2019 and is expected to end in 2024. Consenting participants who require transfusion as medically indicated at three hospitals in Kampala, Uganda, will be randomized to receive either Mirasol-treated WB (n = 1000) or standard WB (n = 1000). TTI testing will be performed on donor units and recipients (pre-transfusion and day 2, day 7, week 4, and week 10 after transfusion). The primary endpoint is the cumulative incidence of one or more targeted TTIs from the Mirasol-treated WB vs. standard WB in a previously negative recipient for the specific TTI that is also detected in the donor unit. Log-binomial regression models will be used to estimate the relative risk reduction of a TTI by 10 weeks associated with Mirasol PRT. The clinical effectiveness of Mirasol WB compared to standard WB products in recipients will also be evaluated.DiscussionScreening infrastructure for TTIs in low-resource settings has gaps, even for major TTIs. PRT presents a fast, potentially cost-effective, and easy-to-use technology to improve blood safety. MERIT is the largest clinical trial designed to evaluate the use of Mirasol PRT for WB. In addition, this trial will provide data on TTIs in Uganda.Trial registrationMirasol Evaluation of Reduction in Infections Trial (MERIT) NCT03737669. Registered on 9 November 2018

SARS-CoV-2 variants inactivation of plasma units using a riboflavin and ultraviolet light-based photochemical treatment

BackgroundTest the ability of Mirasol Pathogen Reduction Technology (PRT, Terumo BCT, Lakewood Co, USA) treatment with riboflavin and ultraviolet light (R + UV) in reducing SARS-CoV-2 infectivity while maintaining blood product quality. Material and methodsSARS-CoV-2 strains were isolated and titrated to prepare cell free virus for plasma units infection. The units were then under treatment with Mirasol PRT. The infectious titers were determined before and after treatment with an in house microtitration assay on Vero E6 cells. Thirty-six plasma pool bags underwent PRT treatment. ResultsIn all the experiments, the measured titer following riboflavin and UV treatment was below the limit of detection of microtitration assay for all the different SARS-CoV-2 strains. Despite the high copies number detected by RT-PCR for each viral strain after treatment, viruses were completely inactivated and not able to infect VERO E6 cells. ConclusionRiboflavin and UV light treatment effectively reduced the virus titers of human plasma to the limit of detection in tissue culture, regardless of the strain. These data suggest that pathogen reduction in blood products highlight the safety of CP therapy procedures for critically ill COVID-19 patients, while maintaining blood product quality.

In vitro characteristics and in vivo platelet quality of whole blood treated with riboflavin and UVA/UVB light and stored for 24 hours at room temperature.

There is a global increase in whole blood usage and at the same time, emerging pathogens give cause for pathogen reduction technology (PRT). The Mirasol PRT has shown promising results for plasma and platelet concentrate products. Treatment of whole blood with subsequent platelet survival and recovery analysis would be of global value. A two-arm, open-label laboratory study was performed with 40 whole blood collections in four groups: non-leukoreduced non-PRT-treated, non-leukoreduced PRT-treated, leukoreduced non-PRT-treated, and leukoreduced PRT-treated. Leukoreduction and/or PRT-treatment was performed on the day of collection, then all WB units were stored at room temperature for 24 h. Sampling was performed after hold-time and after 24-h storage in RT. If PRT-treatment or leukoreduction, samples were also taken subsequently after treatment. Thirteen healthy volunteer blood donors completed the in vivo study per protocol. All WB units were non-leukoreduced and PRT-treated. Radioactive labeling of platelets from RT-stored, PRT-treated whole blood, sampling of subjects, recovery, and survival calculations were performed according to the Biomedical Excellence for Safer Transfusion Collaborative protocol. In vitro characteristics show that PRT-treatment leads to increased levels of hemolysis, potassium, and lactate, while there are decreased levels of glucose, FVIII, and fibrinogen after 24 h of storage. All values are within requirements for WB. In vivo recovery and survival of platelets were 85.4% and 81.3% of untreated fresh control, respectively. PRT-treatment moderately reduces whole blood quality but is well within the limits of international guidelines. Recovery and survival of platelets are satisfactory after Mirasol treatment.

Pathogen reduction of platelets: experience of a single blood bank

: Pathogen reduction technology (PRT) has the potential to prevent pathogen transfusion transmission from blood donor to patient by impeding the replication of bacteria, viruses and parasites in blood components. Additionally, PRT can help to guarantee blood safety in challenging situations for blood supply, as in the Ebola or Chikungunya epidemics, or in a scenario full of uncertainties such as the current SARS-CoV-2 pandemic. The Balearic Islands Blood Bank (BIBB) is one of the few blood establishments worldwide with more than 10 years of experience in the routine use of amotosalen/UVA (Intercept Blood System) and riboflavin/UVA-UVB (Mirasol PRT system) for platelets (PLTs), the use of riboflavin/UVA-UVB for plasma and with research experience in riboflavin/UVA-UVB applied to whole blood. Over the years, we have had the opportunity to evaluate PRT from different perspectives, such as clinical and hemovigilance research in adults and children, in vitro studies on PRT effects on PLTs and assessing the financial impact of PRT implementation. PRT methods offer remarkable benefits but also have certain limitations, which are important to bear in mind during the decision-making process for PRT implementation. The purpose of this study is to review the current knowledge on PRT for PLTs drawing on our experience acquired over the last decade.

Improvement of Blood Processing and Safety by Automation and Pathogen Reduction Technology

Introduction: The objective of the present study was to describe the experience of the Blood and Tissues Bank of Aragon with the Reveos® Automated Blood Processing System and Mirasol® Pathogen Reduction Technology (PRT) System, comparing retrospectively routine quality data obtained in two different observation periods. Methods: Comparing quality data encompassing 6,525 blood components from the period 2007–2012, when the semi-automated buffy coat method was used in routine, with 6,553 quality data from the period 2014–2019, when the Reveos system and subsequently the Mirasol system were implemented in routine. Results: Moving from buffy coat to Reveos led to decreased discard rates of whole blood units (1.2 to 0.1%), increased hemoglobin content (48.1 ± 7.6 to 55.4 ± 6.6 g/unit), and hematocrit (58.9 ± 6.5% to 60.0 ± 4.9%) in red blood cell concentrates. Platelet concentrates (PCs) in both periods had similar yields (3.5 ×10¹¹). Whereas in the earlier period, PCs resulted from pooling 5 buffy coats, in the second period 25% of PCs were prepared from 4 interim platelet units. The mean level of factor VIII in plasma was significantly higher with Reveos (92.8 vs. 97.3 IU). Mirasol PRT treatment of PCs reduced expiry rates to 1.2% in 2019. One septic transmission was reported with a non-PRT treated PCs, but none with PRT-treated PCs. Conclusion: Automation contributed to standardization, efficiency, and improvement of blood processing. Released resources enabled the effortless implementation of PRT. The combination of both technologies guaranteed the self-sufficiency and improvement of blood safety.

Pathogen reduction of SARS-CoV-2 virus in plasma and whole blood using riboflavin and UV light.

BackgroundSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has recently been identified as the causative agent for Coronavirus Disease 2019 (COVID-19). The ability of this agent to be transmitted by blood transfusion has not been documented, although viral RNA has been detected in serum. Exposure to treatment with riboflavin and ultraviolet light (R + UV) reduces blood-borne pathogens while maintaining blood product quality. Here, we report on the efficacy of R + UV in reducing SARS-CoV-2 infectivity when tested in human plasma and whole blood products.Study design and methodsSARS-CoV-2 (isolate USA-WA1/2020) was used to inoculate plasma and whole blood units that then underwent treatment with riboflavin and UV light (Mirasol Pathogen Reduction Technology System, Terumo BCT, Lakewood, CO). The infectious titers of SARS-CoV-2 in the samples before and after R + UV treatment were determined by plaque assay on Vero E6 cells. Each plasma pool (n = 9) underwent R + UV treatment performed in triplicate using individual units of plasma and then repeated using individual whole blood donations (n = 3).ResultsRiboflavin and UV light reduced the infectious titer of SARS-CoV-2 below the limit of detection for plasma products at 60–100% of the recommended energy dose. At the UV light dose recommended by the manufacturer, the mean log reductions in the viral titers were ≥ 4.79 ± 0.15 Logs in plasma and 3.30 ± 0.26 in whole blood units.ConclusionRiboflavin and UV light effectively reduced the titer of SARS-CoV-2 to the limit of detection in human plasma and by 3.30 ± 0.26 on average in whole blood. Two clades of SARS-CoV-2 have been described and questions remain about whether exposure to one strain confers strong immunity to the other. Pathogen-reduced blood products may be a safer option for critically ill patients with COVID-19, particularly those in high-risk categories.

Inactivation of severe acute respiratory syndrome coronavirus 2 in plasma and platelet products using a riboflavin and ultraviolet light-based photochemical treatment.

Background and ObjectiveSevere acute respiratory distress syndrome coronavirus‐2 (SARS‐CoV‐2), the causative agent of coronavirus disease 2019 (COVID‐19), is a member of the coronavirus family. Coronavirus infections in humans are typically associated with respiratory illnesses; however, viral RNA has been isolated in serum from infected patients. Coronaviruses have been identified as a potential low‐risk threat to blood safety. The Mirasol Pathogen Reduction Technology (PRT) System utilizes riboflavin and ultraviolet (UV) light to render blood‐borne pathogens noninfectious, while maintaining blood product quality. Here, we report on the efficacy of riboflavin and UV light against the pandemic virus SARS‐CoV‐2 when tested in both plasma and platelets units.Materials and MethodsStock SARS‐CoV‐2 was grown in Vero cells and inoculated into either plasma or platelet units. Those units were then treated with riboflavin and UV light. The infectious titres of SARS‐CoV‐2 were determined by plaque assay using Vero cells. A total of five (n = 5) plasma and three (n = 3) platelet products were evaluated in this study.ResultsIn both experiments, the measured titre of SARS‐CoV‐2 was below the limit of detection following treatment with riboflavin and UV light. The mean log reductions in the viral titres were ≥3·40 and ≥4·53 for the plasma units and platelet units, respectively.ConclusionRiboflavin and UV light effectively reduced the titre of SARS‐CoV‐2 in both plasma and platelet products to below the limit of detection in tissue culture. The data suggest that the process would be effective in reducing the theoretical risk of transfusion transmitted SARS‐CoV‐2.

A comprehensive proteomics study on platelet concentrates: Platelet proteome, storage time and Mirasol pathogen reduction technology

Platelet concentrates (PCs) represent a blood transfusion product with a major concern for safety as their storage temperature (20–24°C) allows bacterial growth, and their maximum storage time period (less than a week) precludes complete microbiological testing. Pathogen inactivation technologies (PITs) provide an additional layer of safety to the blood transfusion products from known and unknown pathogens such as bacteria, viruses, and parasites. In this context, PITs, such as Mirasol Pathogen Reduction Technology (PRT), have been developed and are implemented in many countries. However, several studies have shown in vitro that Mirasol PRT induces a certain level of platelet shape change, hyperactivation, basal degranulation, and increased oxidative damage during storage. It has been suggested that Mirasol PRT might accelerate what has been described as the platelet storage lesion (PSL), but supportive molecular signatures have not been obtained. We aimed at dissecting the influence of both variables, that is, Mirasol PRT and storage time, at the proteome level. We present comprehensive proteomics data analysis of Control PCs and PCs treated with Mirasol PRT at storage days 1, 2, 6, and 8. Our workflow was set to perform proteomics analysis using a gel-free and label-free quantification (LFQ) approach. Semi-quantification was based on LFQ signal intensities of identified proteins using MaxQuant/Perseus software platform. Data are available via ProteomeXchange with identifier PXD008119. We identified marginal differences between Mirasol PRT and Control PCs during storage. However, those significant changes at the proteome level were specifically related to the functional aspects previously described to affect platelets upon Mirasol PRT. In addition, the effect of Mirasol PRT on the platelet proteome appeared not to be exclusively due to an accelerated or enhanced PSL. In summary, semi-quantitative proteomics allows to discern between proteome changes due to Mirasol PRT or PSL, and proves to be a methodology suitable to phenotype platelets in an unbiased manner, in various physiological contexts.

Mirasol pathogen reduction technology treatment of human whole blood does not induce acute lung injury in mice.

In resource-limited settings and in the military theater, fresh human whole blood is commonly transfused, but infectious risks are a concern. Sophisticated molecular testing for potential infectious agents in the whole blood is often unavailable. To address this unmet need, pathogen reduction technology (PRT) has been developed, and it is an effective approach to inactivate a broad range of pathogens found in human blood. However, studies are needed to determine if it is harmful to blood cells and whether these cells could damage the transfused recipient, including the development of acute lung injury/acute respiratory distress syndrome. In this study, we used a commercial PRT system to treat human whole blood that was then transfused into immunodeficient mice, and the development of acute lung injury was determined. In a model of transfusion-related acute lung injury (TRALI), BALB/c SCID mice developed more robust lung injury when challenged with a MHC Class I monoclonal antibody compared to BALB/c wild-type and NOD/SCID mice. Transfusion of control versus Mirasol PRT-treated whole blood (25% blood volume exchange) into BALB/c SCID mice did not produce lung injury at storage day 1. However, mild lung injury at storage days 14 and 21 was observed without significant differences in lung injury measurements between Mirasol PRT-treated and control groups. The mild storage-dependent acute lung injury correlated with trends for increased levels of cell-free hemoglobin that accumulated in both the control and Mirasol PRT-treated groups. Neutrophil extracellular traps were elevated in the plasma of BALB/c SCID mice in the monoclonal antibody TRALI model, but were not different in mice that received exchange transfusions. In conclusion, exchange transfusion of human whole blood into immunodeficient mice produces mild lung injury that is storage-dependent and not related to pathogen reduction treatment.

Effects of riboflavin and ultraviolet light treatment on platelet thrombus formation and thrombus stability on collagen.

Pathogen reduction technologies (PRTs) are considered for the implementation of safer platelet (PLT) transfusion. PRT treatment involves the addition of a photosensitizer to a blood component followed by ultraviolet (UV) light irradiation. However, the effects of PRT treatment on PLT thrombus formation and thrombus stability have not been satisfactorily clarified. Leukoreduced PLT concentrates (PCs) were treated with riboflavin and UV light (Mirasol PRT). PLT thrombus formation on collagen was evaluated by the microchannel method, by which the total amount of PLTs deposited was measured as indices of thrombus formation and thrombus stability. Using a cone-plate shear-induced PLT aggregometer, PLT reactivity in blood flow was examined in a wide range of shear stresses of 6 to 108 dyn/cm2 . There was no significant difference in surface coverage between PRT-treated PLTs and control PLTs on collagen. On the other hand, the total amount of PRT-treated PLTs deposited was higher than that of control PLTs. The promotive effect of PRT treatment on PLT deposition completely disappeared in the presence of tirofiban, a potent integrin αIIbβ3 inhibitor. The percentage of the dissociation of PRT-treated PLTs on collagen was lower than that of control PLTs after flushing with phosphate-buffered saline. PRT treatment significantly inhibited PLT aggregation under high-shear-stress conditions. Riboflavin-based PRT treatment of PCs leads to the enhancement of PLT thrombus formation and thrombus stability on collagen. However, it does not enhance the reactivity of PLTs not in contact with collagen under high-shear-stress conditions.

Clinical effectiveness of platelets in additive solution treated with two commercial pathogen-reduction technologies.

Two noninferiority, randomized, controlled trials were conducted in parallel comparing the safety and efficacy of platelets treated with Intercept or Mirasol pathogen-reduction technologies versus standard platelets. The primary endpoint was the percentage of hematology patients who developed World Health Organization Grade 2 or greater bleeding. A noninferiority margin of 11% was chosen based on expected Grade 2 or greater bleeding in 20% of controls. The study was closed for financial restrictions before reaching the planned sample size of 828 patients, and an intention-to-treat analysis was conducted on 424 evaluable patients. In the Intercept trial (113 treated vs. 115 control patients), the absolute risk difference in Grade 2 or greater bleeding was 6.1%, with an upper one-sided 97.5% confidence limit of 19.2%. The absolute risk difference in the Mirasol trial (99 treated vs. 97 control patients) was 4.1%, and the upper one-sided 97.5% confidence limit was 18.4%. Neither absolute risk difference was statistically significant. In both trials, posttransfusion platelet count increments were significantly lower in treated versus control patients. Mean blood component use in treated patients versus controls was 54% higher (95% confidence interval, 36%-74%; Intercept) and 34% higher (95% confidence interval, 16%-54%; Mirasol) for platelets and 23% higher (95% confidence interval, 8%-39%; Intercept) and 32% higher (95% confidence interval, 10%-57%; Mirasol) for red blood cells. Unexpected reactions and adverse events were not reported. Mortality did not differ significantly between treated and control patients. Although conclusions on noninferiority could not be drawn due to low statistical power, the study provides additional information on the safety and efficacy of pathogen-reduced platelets treated with two commercial pathogen-reduction technologies.

Inactivation of Middle East respiratory syndrome coronavirus (MERS-CoV) in plasma products using a riboflavin-based and ultraviolet light-based photochemical treatment.

BACKGROUNDMiddle East respiratory syndrome coronavirus (MERS‐CoV) has been identified as a potential threat to the safety of blood products. The Mirasol Pathogen Reduction Technology System uses riboflavin and ultraviolet (UV) light to render blood‐borne pathogens noninfectious while maintaining blood product quality. Here, we report on the efficacy of riboflavin and UV light against MERS‐CoV when tested in human plasma.STUDY DESIGN AND METHODSMERS‐CoV (EMC strain) was used to inoculate plasma units that then underwent treatment with riboflavin and UV light. The infectious titers of MERS‐CoV in the samples before and after treatment were determined by plaque assay on Vero cells. The treatments were initially performed in triplicate using pooled plasma (n = 3) and then repeated using individual plasma units (n = 6).RESULTSIn both studies, riboflavin and UV light reduced the infectious titer of MERS‐CoV below the limit of detection. The mean log reductions in the viral titers were ≥4.07 and ≥4.42 for the pooled and individual donor plasma, respectively.CONCLUSIONRiboflavin and UV light effectively reduced the titer of MERS‐CoV in human plasma products to below the limit of detection, suggesting that the treatment process may reduce the risk of transfusion transmission of MERS‐CoV.

Hemovigilance survey of pathogen-reduced blood components in the Warsaw Region in the 2009 to 2013 period.

In 2009 the Mirasol Pathogen Reduction Technology (PRT) was introduced to the routine blood component production of the Regional Blood Transfusion Center in Warsaw (RBTCW). The goal of this study was to investigate the safety of Mirasol-treated blood components. The accumulated passive hemovigilance data of Mirasol-treated blood components collected at the RBTCW are presented and compared to historical and contemporary data. Furthermore, active hemovigilance data collected from patients with different hematologic disorders transfused with Mirasol-treated or untreated blood components at the Institute of Hematology and Transfusion Medicine (IHTM) are presented and discussed. The adverse reaction (AR) reporting rate by hospitals to the RBTCW after the implementation of the Mirasol technology was 0.39% for Mirasol-treated platelet concentrates (M-PCs) and 0.05% for Mirasol-treated fresh-frozen plasma. When comparing contemporary rates of ARs recorded by RBTCW in the time period 2011 to 2012, no statistical difference was observed between Mirasol-treated and untreated blood components. No serious AR was attributed to Mirasol-treated components. At the IHTM a lower rate of ARs after transfusion of M-PCs was observed than with untreated PCs. Despite the fact that very large amounts of Mirasol-treated plasma have been transfused to patients with congenital or acquired thrombotic thrombocytopenic purpura, no significant increase in AR rates was observed. Treatment of blood components with the Mirasol PRT System has proven to be safe for patients and is not associated with increased rates and grades of adverse events in patients of hospitals in the Warsaw Region.

Real-time measurement of platelet shape change by light scattering under riboflavin and ultraviolet light treatment.

The adoption of pathogen reduction technologies (PRTs) is considered for the implementation of safer platelet (PLT) transfusion. However, the effects of PRT treatment including irradiation with ultraviolet (UV) light on PLT shape have not yet been fully clarified. Leukoreduced PLT concentrates (PCs) were treated with riboflavin and UV light (Mirasol PRT, TerumoBCT). PLT shape and adenosine diphosphate (ADP)-induced shape change were evaluated by a light scattering method where the amplitude of the scattered signal intensity was measured as the indicator of the proportion of discoid PLTs. Using a modified fluorometer, the real-time effects of different wavelengths of UV light on PLT shape were examined over the range of 300 to 360 nm at the same dose. The proportion of discoid PLTs in the Mirasol PRT-treated PCs decreased immediately after treatment. The difference in the proportion between PRT-treated and untreated PLTs became larger with storage. Although this modification correlated significantly with the pH decrease and P-selectin expression, the Mirasol PRT-treated PLTs retained sufficient ability to undergo an ADP-induced shape change. In the study using the modified fluorometer, the proportion of discoid PLTs significantly decreased with the wavelength (< 320 nm) of irradiated UV light. Mirasol PRT treatment of PCs decreases the proportion of discoid PLTs, which seemed to be caused by the irradiation with UV light of short wavelengths (< 320 nm), not that of long wavelengths (≥ 320 nm) in the Mirasol PRT system. Modification of UV light wavelength may improve the quality of PRT-treated PCs.

Transfusion of Human Platelets Treated with Mirasol Pathogen Reduction Technology Does Not Induce Acute Lung Injury in Mice.

Pathogen reduction technology (PRT) has been developed in an effort to make the blood supply safer, but there is controversy as to whether it may induce structural or functional changes to platelets that could lead to acute lung injury after transfusion. In this study, we used a commercial PRT system to treat human platelets that were then transfused into immunodeficient mice, and the development of acute lung injury was determined. P-selectin expression was higher in the Mirasol PRT-treated platelets compared to control platelets on storage day 5, but not storage day 1. Transfusion of control vs. Mirasol PRT-treated platelets (day 5 of storage, 109 platelets per mouse) into NOD/SCID mice did not result in lung injury, however transfusion of storage day 5 platelets treated with thrombin receptor-activating peptide increased both extravascular lung water and lung vascular permeability. Transfusion of day 1 platelets did not produce lung injury in any group, and LPS priming 24 hours before transfusion had no effect on lung injury. In a model of transfusion-related acute lung injury, NOD/SCID mice were susceptible to acute lung injury when challenged with H-2Kd monoclonal antibody vs. isotype control antibody. Using lung intravital microscopy, we did not detect a difference in the dynamic retention of platelets in the lung circulation in control vs. Mirasol PRT-treated groups. In conclusion, Mirasol PRT produced an increase in P-selectin expression that is storage-dependent, but transfusion of human platelets treated with Mirasol PRT into immunodeficient mice did not result in greater platelet retention in the lungs or the development of acute lung injury.

Efficacy of the Mirasol pathogen reduction technology system against severe fever with thrombocytopenia syndrome virus (SFTSV).

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne virus in the Bunyaviridae family. This virus has recently been found in China, Japan and Korea. The risk of transfusion-transmitted SFTSV infection (TTI-SFTSV) is a concern because person-to-person transmission resulting from contact with SFTSV-contaminated blood has been reported. Therefore, we investigated the efficacy of the Mirasol pathogen reduction technology (PRT) system for inactivating SFTSV in vitro. The Mirasol PRT system achieved a > 4.11 log10 reduction value (LRV) for SFTSV. In conclusion, we showed that the Mirasol PRT system could potentially be used to reduce the risk of TTI-SFTSV.