Pathogen Inactivation Technologies Research Articles

Oxygen removal during pathogen inactivation with riboflavin and UV light preserves protein function in plasma for transfusion

Photochemical pathogen inactivation technologies (PCT) for individual transfusion products act by inhibition of replication through irreversibly damaging nucleic acids. Concern on the collateral impact of PCT on the blood component's integrity has caused reluctance to introduce this technology in routine practice. This work aims to uncover the mechanism of damage to plasma constituents by riboflavin pathogen reduction technology (RF-PRT). Activity and antigen of plasma components were determined following RF-PRT in the presence or absence of dissolved molecular oxygen. Employing ADAMTS13 as a sentinel molecule in plasma, our data show that its activity and antigen are reduced by 23±8% and 29±9% (n=24), respectively, which corroborates with a mean decrease of 25% observed for other coagulation factors. Western blotting of ADAMTS13 shows decreased molecular integrity, with no obvious indication of additional proteolysis nor is riboflavin able to directly inhibit the enzyme. However, physical removal of dissolved oxygen prior to RF-PRT protects ADAMTS13 as well as FVIII and fibrinogen from damage, indicating a direct role for reactive oxygen species. Redox dye measurements indicate that superoxide anions are specifically generated during RF-PRT. Protein carbonyl content as a marker of disseminated irreversible biomolecular damage was significantly increased (3·1±0·8 vs. 1·6±0·5nmol/mg protein) following RF-PRT, but not in the absence of dissolved molecular oxygen (1·8±0·4nmol/mg). RF-PRT of single plasma units generates reactive oxygen species that adversely affect biomolecular integrity of relevant plasma constituents, a side-effect, which can be bypassed by applying hypoxic conditions during the pathogen inactivation process.

Induction of Nucleic Acid Damage in Viral Genomes using Riboflavin in Combination with UV Light

Background and Aims: Despite the screening of blood donors, blood transfusion represents an ideal port of entry for blood-borne infection. Blood-borne pathogen transmission has been a concern since the earliest days of transfusion. The blood product of platelet (PLT) concentrates is still faced with the risk of bacterial and viral contaminations. Pathogen inactivation technologies offer a proactive approach and the potential to further improve blood safety. Here we study the pathogen inactivating capacity of riboflavin with UV light treatment in platelet concentrates contaminated with enveloped and non-enveloped viruses. Materials and Methods: The inactivation effects of riboflavin in combination with UV light was examined on Herpes simplex virus (HSV), Vesicular stomatitis virus (VSV) and Polio virus classified as enveloped and non-enveloped DNA and RNA viruses, respectively. After spiking viruses in PLT concentrate, treatment was undertaken with riboflavin (50 µM) and exposed to different doses of UV light. Residual viral infectivity was titrated using 50%Tissue Culture Infective Dose (TCID50). Results: Combination of Riboflavin and UV light treatment reduced the titer of HSV, VSV and Poliovirus with different doses of UV light. Log reduction of HSV with UV doses of 0.82, 1.63, 2.44 and 3.25 J/cm 2 was 0.5, 1.3, 3.5 and 3.8, respectively. Log reduction of VSV for 0.82, 1.63, 2.44 and 3.25 J/cm 2 was 2.8, 3.8, 4.6 and 5.6, respectively. Also, log reduction of poliovirus in the same order for 0.82, 1.63, 2.44 and 3.25 J/cm 2 was 1.7, 2.5, 2.7 and 3.1 respectively. Conclusion: The final dose of UV (3.25 J/cm 2 ) resulted in a larger amount of viral inactivation for enveloped and non-enveloped viruses, in suspended PLT. This method offers a potential to be used for prevention of the majority of PLT transfusion-associated viral pathogens.

Reducing the financial impact of pathogen inactivation technology for platelet components: our experience

Pathogen inactivation (PI) technology for blood components enhances blood safety by inactivating viruses, bacteria, parasites, and white blood cells. Additionally, PI for platelet (PLT) components has the potential to extend PLT storage time from 5 to 7 days. A retrospective analysis was conducted into the percentage of outdated PLT components during the 3 years before and after the adoption of PLT PI technology in our institution. The PLT transfusion dose for both pre-PI and post-PI periods was similar. A retrospective analysis to study clinical safety and component utilization was also performed in the Balearic Islands University Hospital. As a result of PI implementation in our institution, the PLT production cost increased by 85.5%. However, due to the extension of PLT storage time, the percentage of outdated PLT units substantially decreased (-83.9%) and, consequently, the cost associated with outdated units (-69.8%). This decrease represented a 13.7% reduction of the initial cost increase which, together with the saving in blood transportation (0.1%), led to a saving of 13.8% over the initial cost. Therefore, the initial 85.5% increase in the cost of PLT production was markedly reduced to 71.7%. The mean number of PLT concentrates per patient was similar during both periods. The extension of PLT storage time can substantially contribute to reducing the financial impact of PI by decreasing the percentage of outdated PLTs while improving blood safety. Since the adoption of PI, there have been no documented cases of PLT transfusion-related sepsis in our region.

Analysis of reasons for not implementing pathogen inactivation for platelet concentrates

In the last 10 years three technologies capable of inactivating pathogens in platelet concentrates have been authorized in Europe although only one based on the addition of amotosalen and illumination with ultraviolet A (UVA) light, has been approved by the National Agency for the Safety of Medicines and Health Products (ANSM). An intense debate exists about the implementation of pathogen inactivation technologies for labile blood components in general and for platelet concentrates in particular. In this review, we will analyze some of the most frequently argued reasons for not implementing pathogen inactivation for platelet components, i.e.: current platelet components are safe enough; pathogen inactivation technologies might be toxic for the recipient; and pathogen inactivation technologies affect platelet function and increase the risk of bleeding. The analysis and discussion of the evidence currently available to answer those reservations will be limited to the pathogen inactivation technology based on amotosalen and UVA.

The application of high-concentration short-time chlorine dioxide treatment for selected specialty crops including Roma tomatoes (Lycopersicon esculentum), cantaloupes (Cucumis melo ssp. melo var. cantaloupensis) and strawberries (Fragaria × ananassa)

The effects of high-concentration short-time chlorine dioxide (ClO2) gas treatment on food-borne pathogens inoculated onto the surface of tomatoes, cantaloupes, and strawberries were studied. Produce were spot-inoculated with a mixture of Salmonella enterica (serotypes Montevideo, Javiana and Baildon), Escherichia coli O157:H7 (serotypes 204 P, EDL 933 and C792) or Listeria monocytogenes (serotypes Scott A, F 5069 and LCDC 81-861), and treated with ClO2 gas at 10 mg/l for 180 s. After ClO2 gas treatment, surviving populations were determined and shelf-life studies were conducted (microbial spoilage population, change in color and overall appearance). Significant microbial reduction (p < 0.05) was observed for all treated samples. Nearly a 5LogCFU/cm2Salmonella reduction was found on tomatoes, cantaloupe and strawberries, while a ∼3LogCFU/cm2 reduction was observed for E. coli and Listeria on all produce surfaces. E. coli and Listeria appeared to be more resistant to ClO2 gas as compared to Salmonella spp. Treatments significantly (p < 0.05) reduced initial microflora population, while produce color surface was not significantly influenced, as compared to the control (p > 0.05). Results obtained suggest the potential use of high-concentration short-time ClO2 gas treatment as an effective online pathogen inactivation technology for specialty crops in large-scale produce packing operations.

The utility of pathogen inactivation technology: a real-life example of Leishmania infantum inactivation in platelets from a donor with an asymptomatic infection.

Visceral leishmaniasis is typically caused by Leishmania infantum (L. infantum) in the Mediterranean littoral. The majority of infections with L. infantum are asymptomatic and resolve spontaneously in individuals with normal immune systems. A minority progress to classic, full-blown visceral leishmaniasis, known in many areas as kalaazar1,2. Leishmania infection is most often transmitted to humans via the bite of the phlebotomine female sand fly, however transmission of Leishmania by transfusion has also been reported3–13. Populations at risk of clinically apparent disease caused by L. infantum after insect bites or transfusion include infants and immunosuppressed patients. Most cases of transfusion-transmitted leishmaniasis have been reported in endemic areas and, because the infection is often asymptomatic in healthy individuals, it is difficult to calculate the transmission risk precisely. The existence of cryptic Leishmania infections, associated with intermittent low density circulation of the parasite 1,14, has been the main cause of transmission by blood. In the Balearic Islands, our region, the prevalence of asymptomatic L. infantum infection in blood donors is high (11% of blood donors tested had a positive reaction to the delayed-type hypersensitivity test, 3.1% had specific antibodies and L. infantum DNA was detected in the blood of 5.9% of donors studied)15 which is in agreement with other findings regarding asymptomatic individuals from the Mediterranean region1,16,17. Although some research studies have investigated Leishmania infection in blood donors1,14–17, currently there is no suitable Leishmania donor screening test that meets Blood Bank requirements with respect to aspects such as speed, automation and standardisation. At present, the only measure applied to prevent transmission-transfusion leishmaniasis is based on donor selection criteria. According to the “Guide to Preparation, Use and Quality Assurance of Blood Components” from the European Committee on Blood Transfusion, as well as the Spanish Regulation on Blood Donation, the strategy adopted in Europe is based on permanent deferral for donors who have had or currently have visceral leishmaniasis. In other countries, such as the USA, donors are deferred for a period of 1 year from the date of their last departure from an endemic country. Since there is currently no adequate donor screening test for Leishmania, several methods have been used to inactivate Leishmania in blood products18–20 and to eliminate the parasites through filtration using whole blood, fresh plasma and red blood cell (RBC) leucodepletion systems15,21–23. As an approach to reducing the risk of transfusion-related transmission in our area, we investigated the ability of pathogen inactivation technology using riboflavin and ultraviolet light to eliminate L. infantum in apheresis platelet units obtained from an asymptomatic infected blood donor. This is the first report on the utility of pathogen inactivation technology in the elimination of a parasite from a blood component collected from an asymptomatic infected blood donor.

Pathogen inactivation technology applied to a blood component collected from an asymptomatic carrier of Leishmania infantum: a case report

Asymptomatic Leishmania infections have been the main cause of transfusion transmission in endemic areas. Polymerase chain reaction has been used to detect L.infantum DNA in the peripheral blood of asymptomatic Leishmania carriers. In our region, the prevalence of asymptomatic L.infantum infection in donors is markedly high (5·9% of donors studied). We investigated the ability of pathogen inactivation technology, using amotosalen and UVA illumination, to eliminate L.infantum in a blood component collected from an asymptomatic L.infantum infected donor. This is the first report of the INTERCEPT system being used to eliminate a parasite from a component collected from a donor.

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.

Effect of pathogen inactivation on the storage lesion in red cells and platelet concentrates

A primary function of blood transfusion services is to ensure the safety of the community’s blood supply. Multilayer strategies of safety need to be incorporated into the processing of blood components in order to minimize untoward transfusion events related to infections or the blood storage lesion. While there have been considerable technical advances over the past few decades to advance blood component safety, there is a need for continued improvement. One significant problem area is transfusion transmitted bacterial infections. In infectious disease, blood borne bacteria are the major cause of morbidity in transfusion medicine. Proactive implementation of pathogen inactivation technologies, PIT can help to eliminate bacterial contamination of blood. This is accomplished by inactivation of various known and emerging bacterial pathogens, which have been identified through their nucleic acid sequences. The current PIT has additional positive impacts on transfusion safety by reducing adverse clinical events associated with viable residual leukocytes in the blood. Given the valuable benefits of pathogen inactivation, there is a practicable need to advance this technology. In order for a particular pathogen inactivation strategy to gain widespread acceptance, it must satisfy a number of important criteria. The technology shall be: (1) Effective to eliminate pathogens. (2) Uncomplicated and cost-effective to implement in the preparation of blood components. (3) Minimally toxic while maintaining the quality of blood storage products for transfusion purposes. (4) Safe. Currently, PIT is not suitable for all blood components. Future advances in PIT for whole blood and red cell components should expand the application of this technology across a broader range of blood products. Based on available laboratory and clinical data, current pathogen inactivation procedures appear to leave the cell components sufficiently viable to achieve an effective transfusion. Novel technologies continue to evolve for the inactivation of pathogens in the blood supply. We need to ensure these procedures do not worsen the storage lesion causing potential harm to patients. Quality research and development supporting multi-centre clinical trials are necessary. One purpose of such trials is to determine whether this new generation of procedures for processing blood yields bioequivalency regarding the quality of the products. Validated haematological assays should be utilized to test the extent of the blood storage lesion. Post-marketing surveillance involving active haemovigilance is necessary regarding possible adverse outcomes of transfusion.

Current concepts in transfusion transmitted diseases

During the 1950s, 25% of recipients of four or more whole blood transfusions in New York City, USA, developed jaundice, and this was accepted as a ‘fact of life’. At that time, the only transfusion transmitted infectious diseases (TTID) of importance were syphilis and ‘serum hepatitis’, later recognized as hepatitis B. Syphilis screening was introduced in the 1940s and the first assays for hepatitis B surface antigen in the early 1970s. In the early 1980s, the tragedy of AIDS brought serious consequences for blood recipients but also brought attention and resources to the prevention of TTID, resulting in the introduction of additional screening tests in the U.S. and in several other countries [1]. As new screening tests, donor screening procedures and quality systems were developed, they were cumulatively added to the list of donor eligibility and blood processing requirements. Obsolete procedures were removed only under exceptional circumstances. Gradually, multiple layers of safety became part of regulatory requirements including in addition to testing and quality systems, more extensive donor history questionnaires in which donors are asked about potential exposure to transmissible agents (e.g. history of risk behaviours, travel); deferral files listing donors who were deferred because of travel, risk behaviour or reactive screening tests results; quarantine of untested and unsuitable components, kept separately to avoid inappropriate release for transfusion. It should be noted that donor history questions [2] and deferral files [3] have lower sensitivity and poorer predictive value than donor screening tests. In addition, requirements for donor notification and counselling after positive test results were instituted under the presumption that knowledge about their positive results would discourage positive donors from returning to donate. Also, the movement towards volunteer, non-remunerated donations as opposed to replacement donations (made by donors referred by a patient to ensure admission to a hospital) or paid donations was intensified.

Implementation of Bacterial Detection Methods into Blood Donor Screening – Overview of Different Technologies

Background: Through the implementation of modern technology, such as nucleic acid testing, over the last two decades, blood safety has improved considerably in that the risk of viral infection is less than 1 in a million blood transfusions. By contrast, the residual risk of transfusion-associated bacterial infection is stable at approximately 1 in 2,000 to 1 in 3,000 in platelets. To improve blood safety with regard to bacterial infections, many countries have implemented bacterial screening methods as part of their blood donor screening programmes. Methods: Bacterial detection methods are clustered into three groups: i) culture methods in combination with the ‘negative-to-date’ concept, ii) rapid detection systems with a late sample collection, and iii) bedside screening tests. Results: The culture methods are convincing because of their very high analytical sensitivity. Nevertheless, false-negative culture results and subsequent fatalities were reported in several countries. Rapid bacterial systems are characterised as having short testing time but reduced sensitivity. Sample errors are prevented by late sample collection. Finally, bedside tests reduce the risk for sample errors to a minimum, but testing outside of blood donation services may have risks for general testing failures. Conclusion: Bacterial screening of blood products, especially platelets, can be performed using a broad range of technologies. Each system exhibits advantages and disadvantages and offers only a temporary solution until a general pathogen inactivation technology is available for all blood components.

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.

Evaluation of Chlorine Dioxide Gas Residues on Selected Food Produce

In recent years, the consumption of fresh fruits and vegetables has greatly increased, and so has its association with contamination of several foodborne pathogens (Listeria, Salmonella, and Escherichia coli). Hence, there is a need to investigate effective sanitizer systems for produce decontamination. Chlorine dioxide (ClO(2)), a strong oxidizing gas with broad spectrum and sanitizing properties, has previously been studied for use on selected fruits and vegetables. ClO(2) gas treatments show great potential for surface pathogen reduction; however its use from a residue safety standpoint has yet to be assessed. Thus, the objective of this study was to evaluate residues of ClO(2), chlorite, chlorate, and chloride on selected fresh produce surfaces after treatment with ClO(2) gas. A rinse procedure was used and water samples were analyzed by N, N-diethyl-p-phenylenediamine and ion chromatography method (300.0). Seven different foods--tomatoes, oranges, apples, strawberries, lettuce, alfalfa sprouts, and cantaloupe--were analyzed after ClO(2) treatment for surface residues. Very low residues were detectable for all the food products except lettuce and alfalfa sprouts, where the measured concentrations were significantly higher. Chlorine dioxide technology leaves minimal to no detectable chemical residues in several food products, thus result in no significant risks to consumers. Practical Application: Potential for chlorine dioxide gas treatments as an effective pathogen inactivation technology to produce with minimal risk for consumers.

Use of high-concentration-short-time chlorine dioxide gas treatments for the inactivation of Salmonella enterica spp. inoculated onto Roma tomatoes

Salmonella outbreaks have been recently linked to the consumption of fresh tomatoes. Thus, there is a need to develop systems that reduce the risk of microbial contamination to increase product shelf-life and keep fresh fruit attributes. The objectives of this study were to evaluate high-concentration-short-time chlorine dioxide gas treatments effects on Salmonella-inoculated Roma tomatoes and determine the optimal treatment conditions for microbial inactivation and shelf-life extension. Effects of ClO 2 concentration (2, 5, 8 and 10 mg/l) and exposure time (10, 30, 60, 120 and 180 s) on inoculated Roma tomatoes were studied. Salmonella enterica strains, serotype Montevideo, Javiana and Baildon, were used to experimentally inoculate the food product. After ClO 2 treatments, tomatoes were stored at room temperature for 28 days. Inherent microbial population, change in tomato color, and chlorine dioxide gas residuals were evaluated. ANOVA analysis showed that both ClO 2 concentration and treatment time were significant ( p < 0.01) for Salmonella inactivation. Surviving Salmonella populations of 3.09, 2.17 and 1.16 log CFU/cm 2 were obtained treating tomatoes with 8 mg/l ClO 2 for 60 s, 10 mg/l ClO 2 for 120 s, and 10 mg/l for 180 s, respectively (initial Salmonella population: 6.03 ± 0.11 log CFU/cm 2). The selected treatments significantly reduced background microflora ( p < 0.05), while fruit color and residual contents were not significantly different ( p > 0.05), as compared to the control. Results suggest the potential for high-concentration-short-time treatments ClO 2 gas as an effective pathogen inactivation technology for large-scale produce packing operations.

BLOOD COMPONENTS: Lack of antibody formation to platelet neoantigens after transfusion of riboflavin and ultraviolet light–treated platelet concentrates

BACKGROUND: Pathogen inactivation technologies provide a potential solution to donor screening and blood testing strategies reducing the risk of transfusion‐transmitted infectious diseases. The Mirasol pathogen reduction technology (PRT) system (CaridianBCT) uses riboflavin and UV light to introduce modifications in nucleic acids, reducing the infectious pathogen load in blood components. This study evaluated serum of patients who received PRT‐treated platelet (PLT) concentrates over a time period of 28 days for the appearance of antibodies to neoantigens on PLTs.STUDY DESIGN AND METHODS: Serum specimens were obtained at study inclusion and at the 28‐day follow‐up visit from patients randomly assigned to receive PRT‐treated PLT concentrates and at study inclusion of control subjects receiving untreated PLTs. PLT samples from untreated and PRT‐treated PLTs were collected. PLT samples for each patient were pooled for the analysis. The presence of antibodies in patient serum to neoantigens was determined with a modified Capture‐P assay. The presence of auto‐ or alloantibodies in specific patient samples was determined with PAKAUTO and PAK 12 techniques.RESULTS: Forty‐four patients receiving PRT‐treated PLTs were evaluated; none of these patients demonstrated antibodies to neoantigens. One patient demonstrated a PLT alloantibody to human PLT antigen (HPA)‐5b and autoreactivity to glycoprotein Ia/IIa, consistent with an alloantibody at the beginning, but not at the end of the study interval. Of 22 patients evaluated in the control group, one alloantibody with HPA‐5b reactivity was detected.CONCLUSION: Patients receiving PRT‐treated PLT concentrates did not demonstrate antibodies to neoantigens, suggesting that neoantigen formation is not a critical side effect of this pathogen reduction process.

INTERCEPT plasma: comparability with conventional fresh-frozen plasma based on coagulation function – an in vitro analysis

An effective pathogen inactivation (PI) technology for plasma must inactivate a broad range of pathogens with retention of haemostatic function suitable for therapeutic support. This study evaluated a broad panel of coagulation factors regarding functionality in plasma treated with the INTERCEPT Blood System (I-FFP). Apheresis plasma (600 ml) was treated with amotosalen and UVA. Aliquots of plasma were collected prior to and after photochemical treatment and frozen prior to analysis. Pro-coagulants, inhibitors and fibrinolytic proteins, contact pathway components, activation markers, the von Willebrand complex and complement proteins were analyzed. Retention of procoagulant factors in I-FFP ranged from 77 to 92% of pretreatment levels. Components of the von Willebrand complex, including multimers and von Willebrand cleavage protease activity (vWF:CP), remained within normal ranges after treatment. Endogenous inhibitors of coagulation were retained at 93 to 100% of baseline. Plasminogen and alpha-2 antiplasmin were retained at 94 and 78% respectively. Retention of contact factors was variable as some factors were below the reference range prior to PI treatment. With the exception of thrombin-antithrombin complexes (TAT) in one of six replicates all markers of coagulation activation were well within normal ranges. Anaphylatoxins were not increased and C1-esterase inhibitor was fully retained. Treatment of plasma with the INTERCEPT Blood System preserves proteins necessary for haemostasis without inappropriate activation of coagulation, fibrinolytic or complement pathways.

Protecting the blood supply from emerging pathogens: The role of pathogen inactivation

As a consequence of the many blood-safety interventions introduced since the mid-1980s, the major causes of transfusion-associated mortality have shifted from being mainly due to transfusion-transmitted infections (TTIs) to being mainly due to non-infectious serious events such as TRALI, hemolytic reactions, transfusion overload, and graft versus host disease. Thus, TTIs now account for only 10 to 15% of all transfusion associated mortalities! Relevantly, manufacturers of purified plasma protein fractions have, over the same time period, shown that pathogen inactivation technologies can be successfully implemented resulting in little or no transmission of HIV, HCV or HBV since the late 1980s. These technologies, however, cannot be applied to cellular blood components. Thus, new technologies have evolved over the past decade to treat cellular blood components as well as plasma. These technologies, particularly those involving plasma and platelets, have begun to be used in Europe and this proactive paradigm has evolved to become a potential pre-emptive approach for ridding the blood supply of most TTIs (virus, bacteria, and protozoa). However, in order for pathogen inactivation technologies to become widely accepted, they must be shown to be both cost effective and not associated with new risks to recipients!

Transfusion medicine and safety

Advances in safety of blood transfusion in clinical practice principally relate to preventing transfusion-transmitted infections (TTI). Epidemiological studies of TTI have resulted in the development, standardization, and implementation of an expanding array of immunoassays employed worldwide in routine screening of blood donated by voluntary blood donors. Exclusion of infected blood and their donors has remarkably reduced the risk of transmitting HBV, HCV, HIV-1/2, and HTLV-I/II infections. Nucleic acid tests (NAT) using enzymatic amplification of viral gene sequences have augmented the risk reduction in “window period” infections that are undetectable by the serological tests. Improved viral safety of transfusion therapy has led us to recognize the risk of bacterial contamination, especially in platelet concentrates stored optimally at room temperature. Besides the current effort devoted to microbial risk reduction, pathogen inactivation technologies promise reduction of the residual risk of known and emerging infectious agents. The clinical effectiveness of the foregoing measures, international harmonization/standardization of practices and procedures, and continued hemovigilance portend safest possible safety in the clinical practice of blood transfusion.

Pathogen inactivation - the definitive safeguard for cellular blood products?

Although the infectious risks of blood transfusion are remarkably small, the current multi-layered approach of donor screening, testing and deferral is unlikely to have as much impact in the future as it has in the past. Pathogen inactivation (PI) technologies have all but eliminated the infectious risks of plasma-derived protein fractions and will potentially provide additional protection against both known and as-yet-unidentified agents. The treatment of blood components using PI technologies continues to evolve and the impact of PI on product quality and recipient safety remains paramount and is yet to be fully determined. The presentation will focus on the issues surrounding pathogen inactivation of blood components and how they contrast with those involved in plasma fraction manufacturing.

Pathogen inactivation - the definitive safeguard for cellular blood products?

Although the infectious risks of blood transfusion are remarkably small, the current multi-layered approach of donor screening, testing and deferral is unlikely to have as much impact in the future as it has in the past. Pathogen inactivation (PI) technologies have all but eliminated the infectious risks of plasma-derived protein fractions and will potentially provide additional protection against both known and as-yet-unidentified agents. The treatment of blood components using PI technologies continues to evolve and the impact of PI on product quality and recipient safety remains paramount and is yet to be fully determined. The presentation will focus on the issues surrounding pathogen inactivation of blood components and how they contrast with those involved in plasma fraction manufacturing.