Safety Of Blood Components Research Articles

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.

Blood Cell MicroRNAs: What Are They and What Future Do They Hold?

The advent of blood component storage revolutionized health care by allowing for a managed supply of transfusion quality blood products. During storage, blood components undergo a series of physiological changes that affect the product quality, which ultimately can interfere with the safety and efficacy of such products after transfusion. Despite continuous improvements in blood component quality and safety, it is still desirable to have in vitro standard markers of measurable characteristics that predict blood component safety and efficacy in vivo following their transfusion. Over the last decade, research on the feasibility of using microRNAs as biomarkers for various clinical manifestations and cellular pathologies has exploded. Here, we review the literature on blood cell microRNAs and discuss the potential of these molecules to act as measurable characteristics (product biomarkers) for stored blood component quality and safety.

Bottlenecks of blood processing in Uganda

To identify where and why delays occur in Uganda blood banks. The timely provision and supply of safe and efficacious blood components to hospitals depends on sound systems in the processing blood banks. Poorly managed systems lead to apparent blood shortages in hospitals and increase discard rates due to expiry before dispatch. We reviewed records of 4126 units of whole blood delivered by the mobile collection teams to a major regional blood bank, in the period 1 March 2009 to 30 June 2009, to ascertain the time intervals between the critical steps in the blood processing chain. This was followed by interviews with staff in two blood banks to establish the causes of process delays. The average duration between blood collection and final labelling (release from quarantine for final storage) was 15·4 (SD 10·8) days. In timeline, the step between matrix generation and grouping was (median duration 8 days) the longest, whereas grouping to labelling was the shortest (median duration 2 days). Blood expiry had the highest discard rate (0·17%) among the non-transfusion transmissible infection marker causes. A minimally facilitated small staff contributed to the process flaws. A considerable amount of blood does not reach hospitals because of process delays between collection and ultimate dispatch. This is caused by a thin staff working with inadequate materials, out-of-date methods and in an overcrowded environment. Provision of adequate staff and improved financial allocations to the Uganda Blood Transfusion Services will mitigate this situation.

Good practice in plasma collection and fractionation

The control strategy to ensure safety of blood products includes a combination of measures focusing on ensuring the quality and safety of starting material by careful donor selection and testing strategies at different levels, together with validated manufacturing processes, including steps to inactivate or remove potential contaminating agents. Using an approach based on good manufacturing practice (GMP) provides a manufacturing model that allows for a documented system of incorporating quality throughout the entire manufacturing process and describes the activities and controls needed to consistently produce products that comply with specifications and are safe for use. There are no doubts that the aim of providing safe and high‐quality product to the patients should be the same for all products derived from human blood, independent of its use either as a blood component for direct transfusion or as industrially manufactured product. It would be difficult to justify whether for blood components the good practice standards and for plasma derivatives the GMP standards for manufacturing would not ensure equivalent levels of quality and safety. To ensure a high level of quality and safety of blood components and plasma derivatives, the implementation of double standards in blood establishments and fractionation industry would not be effective and should be avoided. Harmonized standards and good practices for collection and fractionation, based on the principles of GMP, should be envisaged in the whole chain of manufacturing blood components and plasma derivatives. Global initiatives to further promote the implementation of harmonized GMP for the collection in blood establishments and a stringent regulatory control are ongoing. This would further contribute to the global availability of plasma‐derived medicinal products.

Evaluation of clinical appropriateness of blood transfusion.

The appropriateness of health procedures has attracted considerable attention in recent years, particularly in the light of the need to control the growth of healthcare costs. Clinical appropriateness can be defined as the use of interventions: - with documented clinical effectiveness - for conditions in which the effectiveness has been documented - with expected benefits exceeding the expected negative consequences. The need to give the 'right' care, to the 'right' patient, in the 'right' way, should be kept clearly in mind independently of the awareness that health costs cannot be indefinitely expanded. In fact, economic considerations pertain to a different factor underlying clinical governance, the organizational appropriateness, which means applying clinically appropriate interventions on the condition that they use a reasonable amount of resources and providing that the consumption of these resources is as efficient as possible. In Italy the need to assess the appropriateness of blood transfusion practice has been established by regulatory requirements and by good practice standards1. Furthermore, the growing need to deliver sufficient and safe blood components of high quality make careful control of their appropriate use even more necessary.

Evaluation of antimicrobial peptides as novel bactericidal agents for room temperature–stored platelets

A single cost-effective pathogen inactivation approach would help to improve the safety of our nation's blood supply. Several methods and technologies are currently being studied to help reduce bacterial contamination of blood components. There is clearly need for simple and easy-to-use pathogen inactivation techniques specific to plasma, platelets (PLTs), and red blood cells. In this report, we introduce a novel proof of concept: using known therapeutic antimicrobial peptides (AMPs) as bactericidal agents for room temperature-stored PLT concentrates (PCs). Nine synthetic AMPs, four from PLT microbicidal protein-derived peptides (PD1-4) and five Arg-Trp (RW) repeat peptides containing one to five repeats, were tested for bactericidal activity in plasma and PC samples spiked with Staphylococcus aureus, S. epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Bacillus cereus. A 3-log reduction of viable bacteria was considered as the bactericidal activity of a given peptide. In both plasma alone and PCs, RW3 peptide demonstrated bactericidal activity against S. aureus, S. epidermidis, E. coli, P. aeruginosa, and K. pneumoniae; PD4 and RW2 against P. aeruginosa; and RW4 against K. pneumoniae. The activity of each of these four peptides against the remaining bacterial species in the test panel resulted in less than a 3-log reduction in the number of viable bacteria and hence considered ineffective. These findings suggest a new approach to improving the safety of blood components, demonstrating the potential usefulness of screening therapeutic AMPs against selected bacteria to identify suitable bactericidal agents for stored plasma, PCs, and other blood products.

Prevention of bacterial contamination, including initial flow diversion

Blood centers and hospitals worldwide face a continuing challenge to improve the safety of blood components for transfusion. Important improvements have been achieved due to careful donor selection, and advances in collection, testing, storage and handling. Transfusion-transmitted infections (TTIs) are now rare in many countries. However, haemovigilance system reports reveal that bacterial contamination of blood components remains an important residual risk, particularly relating to platelet transfusions. For example, the 2008 annual report from the Serious Hazards of Transfusion (SHOT) scheme in the United Kingdom describes a total of 38 confirmed TT bacterial events since 1998 [1]. The majority (32) of these were related to platelets and the others (six) to red cells. Forty patients were affected in total, as some apheresis platelets were split and went to different recipients, with both patients suffering an adverse event. In 2008, all four confirmed cases were due to platelets, with consequences ranging from minor morbidity to death in a total of six patients. This can be contrasted with 22 confirmed TT viral or parasitic infections in 25 patients reported to SHOT since 1998, and no confirmed infections reported between 2006 and 2008. Clearly, therefore, this is an important area where ongoing efforts are warranted to improve transfusion safety. This review will focus on efforts to prevent bacterial contamination occurring, with some consideration of methods to detect it, where present, in order to prevent contaminated units reaching the patient.

The role and impact of the transfusion medicine consultation service in the management of patients in the hematopoietic transplant service: A retrospective analysis

Background Adverse reactions secondary to transfusion of incorrect blood components can be fatal. We have established numerous processes to prevent these reactions in patients with cancer who continuously need blood component support, especially hematopoietic transplant recipients. The development of an active transfusion medicine consultation service at our institution to serve patients undergoing hematopoietic transplantation has led to more organized and simpler management of providing blood components to such patients. Study design and methods Safety tools were employed to attain our goal of providing safe blood components to hematopoietic transplant recipients. These tools were consultation request forms, blood component selection stickers on the patients’ charts, and transfusion medicine physician consultation notes posted in the patients’ medical records. One hundred randomly selected hematopoietic transplant recipients were reviewed over 16 months. Fifty patients received blood components from ABO-compatible donors, whereas the other 50 patients received components from ABO-incompatible donors. Deviation reports regarding the issuance of blood components in these patients over the study period were reviewed retrospectively. Results We identified eight reported deviations from the recommended blood components: red blood cells in one case, fresh frozen plasma in one case, single donor platelets in one case, and random donor platelets in five cases. Our transfusion service issued all eight components, but none of them were transfused. In all eight cases, the blood components were intended for transfusion to ABO-mismatched hematopoietic transplant recipients. Nurses identified the incorrect blood components by verifying the recommended blood groups on the patients’ chart stickers, returned the components to the transfusion service, and transfused the correct blood components. Conclusion Use of these safety tools has improved the safety culture regarding transfusion of blood components in hematopoietic transplant recipients at our institution.

Comprendre le rôle des institutions publiques européennes en transfusion sanguine

In the context of increased demand of blood components, it is highly desirable to ensure development and implementation of established standards for ethical, organisational and regulatory fields in order to guarantee the sufficiency, quality and safety of blood components and their derivatives as well as the protection of donors and recipients. In Europe, the contributions of the European public institutions is fundamental for the achievement of these goals and for the harmonisation of practices inherent to transfusional medicine activities. The Council of Europe with its 47 member states constitutes the ideal platform to tackle these themes: for half a century, its public health and bioethics experts have contributed to the elaboration of conventions and recommendations which serve as a model to elaboration of national or European regulations relevant to this field.

The impact of training in transfusion medicine

Background Basic training skills and program for all health care providers working in the blood transfusion services is important and essential. All blood transfusion staff should have active participation in a training program that includes teaching all national and international regulations related to blood transfusion administration and guidelines of safe blood and blood products. The blood bank staff (physicians, medical technologists and nurses) should pass proper assessment procedures in order to work in this vita health related services. All staff working in blood transfusion services should receive a proper education and learning skills in this field of medicine. Awareness of blood safety and Good Manufacturing Practice (GMP) in blood transfusion should be greatly increased among them.Methods and Results Sustainable national and international education and training in blood transfusion services are needed and should be considered as a priority. Methods of teaching and training may include courses or workshops consist of a series of lectures, practical sessions, problem based learning and computer based distance learning programs. A proper training and continuous medical education in blood transfusion services have played an important role in minimizing the risk of transfusion related complications in many countries.Conclusions Creating an effective learning and training environment is a real challenge for most developing countries. Transfusion medicine is a branch of medicine which has a great link with almost all medical and surgical specialties. Blood transfusion safety plays an important and significant role in the patient's management. Proper qualified training personnel are the key of delivering safe blood components and the Good Manufacturing Practice (GMP) in blood transfusion services.

Regulatory requirements and standards on clinical appropriateness of blood component transfusion.

Regulatory requirements and standards on clinical appropriateness of blood component transfusion.

Clinical appropriateness of blood component transfusion: regulatory requirements and standards set by the Scientific Society in Italy.

Decision-making in health care is strongly conditioned by values of patients and providers, available resources, and information showing effectiveness/efficacy of a particular health care intervention. Clinical decisions concerning treating patients should, as far as possible, be evidence-based1; this is, to a great extent, current clinical dogma, and many medical practitioners in all disciplines are now, to some extent, utilising it2. Evidence-based medicine (EBM) can be defined as conscientious, explicit and judicious use of current best evidence in making decisions about care of individual patients3. It combines clinical judgment and experience with best available scientific evidence to improve medical decision-making and should provide clinicians, health care systems and policy-makers with instruments to appropriately evaluate scientific evidence supporting various diagnostic and therapeutic activities. This represents a radical departure from usual and customary methods for making treatment decisions concerning patients and has led to EBM being a discipline taught in medical schools and teaching hospitals4. Transfusion medicine (TM) is currently adopting principles and research methodologies that support EBM5, and high-level research has actually been undertaken at same rate as in all medical specialties combined in terms of numbers of randomised controlled trials and meta-analyses1. EBM in TM not only refers to best research evidence, but is often based on a broader range of inputs, including public expectations about transfusion safety and issues concerning precautionary principle; this implies that criteria for evaluating efficacy and cost-effectiveness of interventions in TM may differ substantially from those used in other areas6. The increasing need to deliver sufficient and safe blood components of high quality may be cause of an excessive focus on supply side of blood transfusion chain rather than clinical problem facing patients and clinicians7. An overwhelming concentration on blood supply can lead to appropriate clinical utilisation of blood components being ignored as a potentially useful instrument to maintain blood supply itself, although physicians should always consider clinical appropriateness as a must, under professional, scientific and ethical points of view. Hence, the appropriateness of transfusion practices will only improve, not by expecting clinicians to be gatekeepers of blood supply, but with better patient blood management based on a sound understanding of pathophysiology and better evidence for transfusion efficacy7. Based on above considerations, appropriateness of transfusion practices should systematically mean that blood components are transfused only when there is evidence for potential benefit, there are no valid alternatives, safe and quality products are available, and risks and benefits are carefully assessed before decision to transfuse is made. Recent European regulatory acts in field of blood transfusion (Directive of Council 2002/98/EC8 and Directives of Commission 2005/61/EC9 and 2005/62/EC10), while focusing on fundamental issues concerning quality, safety, traceability, haemovigilance, etc., do not actually take into consideration promotion and assessment of appropriateness of clinical use of blood components11. Indeed, Community's legislative framework excludes actual therapeutic use of blood components. Moreover, its provisions are no longer applicable when components are sent for further processing into medicinal products, when pharmaceutical legislation comes into force12. The appropriateness of clinical use of blood components is addressed by Recommendation Rec(2002)1113, which is indeed an excellent guideline to member states on how and what to do to implement optimal use of blood and blood products in clinical setting, but no mandatory act at European level establishes that appropriateness of transfusion practices must be promoted, monitored, assessed and, when necessary, improved. This review is aimed at providing an overview of Italian regulatory framework and of requirements of Italian standards of TM on assessment of appropriateness of blood transfusion.

Regulation of Blood Components - a Help or Hindrance to Good Clinical Practice?

The application of formal regulatory structures to the field of blood component and blood product manufacture is an understandable response to public and governmental concern over the safety of such products. Internationally the trend is to greater central control of blood service provision and regulation is one of several tools used to achieve this. In both Australia and New Zealand, blood components are treated as medicinal products for the purposes of regulation. The imminent creation of a TransTasman Regulatory Authority provides an opportunity to review systems used for the regulation of these products within Australasia and to ensure that an appropriate balance between clinical need and quality conformance is achieved. The control of human derived medicinal products presents a number of specific challenges. This is particularly the case in relation to blood components where biological variation will impact on the ‘formulation’ of any given product. Essentially each component becomes a unique batch. Efforts at control and regulation should recognise this. Two broad approaches can be used for regulation. In the first control is achieved through the application of standard processes. In the second the necessary outcome is defined but the process not formally defined. Increasingly regulatory control of blood component manufacture favours control of the process. Control through process can however ultimately restrict clinical flexibility and responsiveness. Care must be taken to ensure that this is recognised and addressed in the development of systems utilised to assure the quality and safety of blood components.

Quality

Quality

Inactivation of Infectious CMV in Platelet Products: Comparison of INTERCEPT Blood System™ and Leukofiltration.

Background: While many severely immunocompromised patients require cytomegalovirus (CMV)-safe blood components, the standard approach of providing CMV-seronegative and/or leukoreduced components is still associated with breakthrough cases of CMV transmission. The INTERCEPT Blood System™ is a pathogen-inactivation methodology for platelets and plasma which may be a superior approach for providing CMV-safe transfusions. In this study, we compared the efficacy of INTERCEPT with leukoreduction for inactivating and/or removing infectious CMV experimentally introduced at high levels into platelet components.Methods: Pooled buffy-coat platelet concentrates (n=6) were prepared from volunteer whole blood donations at a blood center using standard methods. A high titer stock (>108 pfu/mL) containing both cell-associated and cell-free human CMV (AD169) was then spiked into each unit. After collection of pre-treatment samples, the CMV-spiked components were divided into 2 bags of equal volumes (2.5–6.0 ×1011 platelets in ∼350 mL of 35% plasma and 65% InterSol™). One platelet unit was treated with INTERCEPT using methods in routine daily use at the blood center; the other unit was leukoreduced by filtration using commercial leukofilters (e.g., Asahi PLX5). Post-treatment samples were then collected. Total DNA prepared from each sample was subjected to nested PCR amplification. Plasma samples were added to confluent MRC5 monolayers, and the cultures were examined daily over the course of 6 weeks for the appearance of viral cytopathic effect.Results: Prior to viral spiking, all 6 pooled BC platelet components were CMV-seronegative and had no detectable CMV by either nested PCR or viral culture. After spiking with CMV, all units had readily detectable CMV DNA by PCR; 5 of the 6 units showed replication-competent virus as determined by CMV culture. INTERCEPT uniformly eliminated amplification of the 2,039 bp fragment of CMV UL93 open reading frame, while CMV DNA could be amplified from some filtered units. Using viral culture as a sensitive indicator of replication-competent CMV, INTERCEPT completely prevented CMV replication in all samples. In contrast, each of the 5 components that displayed infectious CMV after spiking still had detectable replication-competent virus after leukoreduction.Discussion: We found that INTERCEPT treatment could completely inactivate CMV in platelet components treated under standard blood center conditions even when CMV was inoculated into the components at artificially high viral loads (final concentration ∼ 106 pfu/mL). In contrast, leukoreduction was ineffective under these conditions since all inoculated units demonstrated replicating CMV after filtration. These data are consistent with PCR results showing that INTERCEPT also eliminated amplifiable CMV DNA from the platelet components. Thus, INTERCEPT treatment greatly reduces, if not eliminates, the risks of CMV transmission by transfusion, suggesting that INTERCEPT-treated platelets may be optimally CMV safe as compared to leukoreduced units.

Rapid Duffy Genotyping in Sickle Cell Disease Patients Using PCR-SSP Is a Valuable Tool for Blood Component Selection.

Background: Sickle cell disease (SCD) patients are frequently transfused and, finding adequate and safe blood component for them has a great impact in transfusion services and in patients clinical follow-up. DNA genotyping for RBC antigens is a tool for the management of these patients to overcome the limitations of hemagglutination assays. However, the polymerase chain reaction (PCR) by restriction fragment length polymorphism (RFLP) is time consuming. The aim of this study was to develop a rapid PCR specific sequence primer (SSP) approach for Duffy genotyping in SCD patients.STUDY DESIGN AND METHODS: Blood samples from 91 SCD patients were studied by hemagglutination and by PCR-SSP for Duffy system. All samples typed as Fy(b-) were submitted to adsorption and elution techniques to detect the weak expression of Fyb antigen. DNA was extracted by a commercial DNA extraction kit (QIAamp DNA, QIAGEN, Germany). Detection of FY*A, FY*B, FY*B-33, FY*B-265T and FY*B-298A were performed using specific primers by PCR-SSP. DNA amplification was carried out in a final volume of 20μL with identical reaction mixture and cycling conditions as follows: 0.2μg of genomic DNA, 0.2mM of each dNTP, 5% of glycerol, 1.5 units of platinum Taq polymerase (Invitrogen, Brazil) in the buffer supplied, 5.0mM of MgCl2 and 10.0 pmoles of each primer. PCR fragments were separated for 90 minutes at 100V using 0.5μg.mL-1 ethidium bromide-stained 2.0% agarose gel and visualized in a UV light apparatus (Eagle Eye II, EUA).Results: Table 1 shows the results of Duffy phenotyping, Duffy genotyping and gene frequencies in SCD patients The most common phenotype found in our study was Fy(a–b+), 35.2%. In three samples (3.3%) we detected weak Fyb antigen and identified FY*B-265T alelle. All samples phenotyped as Fy(a–b–) genotyped as (FYB-33/FYB-33).CONCLUSION: PCR-SSP is a method that contributes for easily and accurate Duffy genotyping for SCD patients. In our study, all SCD patients with Fy(a–b–) can be safely transfused with Fy(b+) red blood cell components with no risk for developing anti-Fyb saving rare Fy(a–b–) units.Table 1PhenotypeGenotypenGenotype FrequencyFy(a+b+)FYA/FYB160.176Fy(a–b+)FYB/FYB230.253FYB/FYB-265T90.099Fy(a+b–)FYA/FYA180.198FYA/FYB-3340.044Fy(a–b–)FYB-33/FYB-33210.231TOTAL911.00

Blood conservation strategies in cardiac surgery

Despite the continuous efforts to increase the safety of blood components, red blood cell transfusions remain associated with some risks and side effects. Therefore, numerous techniques have been developed to decrease blood use, but they also carry risks and bear costs. Most of them are frequently used in cardiac surgery, which still consumes a large part of the available blood supply. Among western countries the use of alternative techniques, but also transfusion practice, has been shown to vary markedly. 'Blood conservation' is a global concept engulfing all possible strategies aimed at reducing patients' exposure to allogeneic blood components. The development of the 'best strategy' consists of the selection of those techniques that are most appropriate to the local specific situation. It implies the establishment of a reliable system, collecting data both at the surgical team and at the medical level.

Pathogen-reduction systems for blood components: The current position and future trends

The current multi-layered interventional approaches to blood safety have dramatically reduced the risk of viral contamination of blood components. Nowadays most of the residual transfusion transmitted infections (TTI) occur as the result of the interval between the time the donor is infected and the moment at which tests are capable of detecting the agent, the so called “window period” which has been considerably reduced by the increased sensitivity of nucleic acid testing (NAT). However, the residual risk of bacterial contamination and the unexpected appearance of some other emerging pathogens, almost every five years, are still of major concern to the public, politicians, regulatory agencies and place immense pressures on the organisations responsible for the provision of safe blood and its components. In view of these bleak scenarios, the use of human blood as a raw biological source is inherently unsafe, and screening/testing alone cannot exclude all the potential human pathogens; hence we need to put in place some sort of safer alternatives and/or additional preventative safety measures. Recently, several substitutes (alternatives) to virtual blood components have been developed and tried. Moreover, various mechanical methods such as cell washing and leukofiltration have been implemented as additional preventative safety measures but with limited success in abrogating the risk of transfusion transmitted cell-associated agents. The most promising approaches, so far, are methods that target pathogen nucleic acids (Methylene blue; Psolaren and Riboflavin UV light treatment). These procedures have undergone considerable in vitro studies to ensure their extremely high safety margins in terms of toxicity to the cells or to the recipients. In essence, while the technology of targeting nucleic acid to stop viral proliferation is common to the above three strategies, in practice these procedures differ in terms of operational, physicochemical and biological characteristics; including the potential impacts of their metabolites and photo-adducts; their effects on the spectrum of pathogens affected and the log reductions in culture infective studies. Accordingly, any strategy that involves addition of an extraneous agent or physicochemical manipulation of blood must balance the benefits of pathogen reduction against the loss or alteration to the cells and plasma functional integrity, short and long term toxicity to the cells and to the recipients, as well as the risk to the personnel involved and the community at large. Moreover, it must be noted that each method will have a different profile of adverse reactions and may differ in terms of the risk to particularly vulnerable groups of patients, requiring in depth clinical trials, while taking into consideration the cost benefit of the final process. Newer diagnostic procedures must be in place to establish the storage stability of products that have undergone pathogen inactivation, in particular tests reflecting the release of platelet-derived cytokines, cellular apoptosis or microvesiculation and their role in immunosupressiveness. This overview aims to provide an update on the continual improvements in blood component safety, in particular using methods that target pathogen nucleic acid. Emphasis is placed on methylene blue light treatment (MBLT) and Intercept or Mirasol PRT systems for platelets and plasma. The status of pathogen reduction of whole blood and red cells is also highlighted, though the progress in this area has been virtually stopped after the finding of antibody development in the clinical trial.

Sécurité des produits sanguins labiles et parvovirus B19

More than 25 years after the discovery of the parvovirus B19 (B19), the issue of the safety of blood components and the screening of this virus in blood donations is still debated. Although more often transmitted by respiratory route, B19 may also be transmitted by transfusion of blood components. This risk of exposure has been estimated to a frequency ranging from 1/625 to 1/50,000, according to the sensitivity of the detection methods and to seasonal epidemiologic circumstances. Usually, B19 is responsible for benign pathologies. However, such an infection can have a serious clinical outcome in three categories of susceptible recipients: (i) patients with shortened red cell survival (thalassemia major, sickle cell disease, other hemolytic diseases); (ii) immunocompromised patients (previously exposed to B19 or not) (iii) and pregnant women (not previously exposed the B19), with a risk of hydrops fetalis or of intrauterine death. Selected blood components, not collected during the short but highly viremic pre-seroconversion phase, could be reserved for these three groups of at-risk recipients. The screening of such viremic donations could be performed with nucleic acid testing (NAT), but an alternate strategy could be the selection of B19 immunised donors far from the primo-infection (positive for B19 IgG and negative for B19 IgM, or only positive for IgG at two controls distant of several months). However, the existence of persistently B19-infected individuals carrying B19 DNA despite the presence of specific IgG (estimated at 1% of blood donors) could constitute a potential threat for transfused immunocompromised recipients. The screening of such donors, which could be performed through a very highly sensitive NAT, would be justified only if the infectivity of such blood donations is demonstrated. If not, a screening of blood donors positive for B19 IgG would be a sufficient preventive measure.

Cumulative Risks of Early Fresh Frozen Plasma, Cryoprecipitate and Platelet Transfusion in Europe

Both fresh frozen plasma (FFP) and platelets are heavily used in massive transfusion. Although FFP can partially correct abnormal coagulation, a recent systematic review revealed no randomized trials showing clinical benefit. Although the overall risks of FFP and platelets are low, they are the least safe blood components, due to immunologic reactions such as allergy/anaphylaxis, transfusion-related acute lung injury (TRALI) and hemolysis due to anti-A or anti-B if transfused across ABO groups. TRALI, an acute syndrome of dyspnoea, hypoxia and pulmonary 'white-out' is now a major cause of transfusion-related death. Since it is usually triggered by donor HLA antibodies, selecting non- immune donors for FFP production may be beneficial. For platelet components, risks may be reduced by platelet additive solution, allowing removal of 70% of plasma. Platelets have the additional hazard of bacterial contamination, with donor skin the predominant source. Improved arm cleansing, divert pouches for the first 30-50 mL blood and bacterial screening have been adopted internationally. Virus risks are now vanishingly low, although new agents e.g. West Nile virus can still appear. Pathogen reduction for FFP is now well established in Europe, with solvent detergent and methylene blue methods licensed, and the psoralen amotosalen in trial. Loss of clotting factors and natural anti-coagulants are recognized side effects. Amotosalen is also licensed for platelet concentrates, with the added benefit of bacterial killing. In the UK, concern regarding vCJD has led to importation of US FFP for children.