Labile Blood Components Research Articles

Pathogen Reduction for Platelets-A Review of Recent Implementation Strategies.

The development of pathogen reduction technologies (PRT) for labile blood components is a long-pursued goal in transfusion medicine. While PRT for red blood cells and whole blood are still in an early phase of development, different PRT platforms for plasma and platelets are commercially available and routinely used in several countries. This review describes complementary strategies recommended by the US FDA to mitigate the risk of septic reactions in platelet recipients, including PRT and large-volume delayed sampling, and summarizes the main findings of recent reports discussing economical and organizational issues of platelet PRT implementation. Sophisticated mathematical analytical models are available to determine the impact of PRT on platelet costs, shortages and outdates in different settings. PRT implementation requires careful planning to ensure the availability of sufficient economical, technological and human resources. A phased approach was used in most PRT implementation programs, starting with adult and pediatric immunocompromised patients at higher risk of developing septic platelet transfusion reactions. Overall, the reviewed studies show that significant progress has been made in this area, although additional efforts will be necessary to reduce the storage lesion of PRT platelets and to expand the sustainable applicability of PRT to all labile blood components.

Preclinical transmission of prions by blood transfusion is influenced by donor genotype and route of infection.

Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from zoonotic transmission of bovine spongiform encephalopathy (BSE). Documented cases of vCJD transmission by blood transfusion necessitate on-going risk reduction measures to protect blood supplies, such as leucodepletion (removal of white blood cells, WBCs). This study set out to determine the risks of prion transmission by transfusion of labile blood components (red blood cells, platelets, plasma) commonly used in human medicine, and the effectiveness of leucodepletion in preventing infection, using BSE-infected sheep as a model. All components were capable of transmitting prion disease when donors were in the preclinical phase of infection, with the highest rates of infection in recipients of whole blood and buffy coat, and the lowest in recipients of plasma. Leucodepletion of components (<106 WBCs/unit) resulted in significantly lower transmission rates, but did not completely prevent transmission by any component. Donor PRNP genotype at codon 141, which is associated with variation in incubation period, also had a significant effect on transfusion transmission rates. A sensitive protein misfolding cyclic amplification (PMCA) assay, applied to longitudinal series of blood samples, identified infected sheep from 4 months post infection. However, in donor sheep (orally infected), the onset of detection of PrPSc in blood was much more variable, and generally later, compared to recipients (intravenous infection). This shows that the route and method of infection may profoundly affect the period during which an individual is infectious, and the test sensitivity required for reliable preclinical diagnosis, both of which have important implications for disease control. Our results emphasize that blood transfusion can be a highly efficient route of transmission for prion diseases. Given current uncertainties over the prevalence of asymptomatic vCJD carriers, this argues for the maintenance and improvement of current measures to reduce the risk of transmission by blood products.

Review of indications for immunoglobulin (IG) use: Narrowing the gap between supply and demand.

Cellular blood components and plasma-derived medicinal products (PDMPs) are obtained from blood donated by volunteers. In a growing number of countries, in line with World Health Organization advice issued since the mid-1970s, donors are not remunerated. In recent decades, considerable efforts have been made to restrict the indications for labile blood components to those based on evidence, to ensure efficacy and safety. By contrast, the producers of PDMPs have developed pathogen reduction techniques for inactivating the microorganisms in (pooled) plasma, but little attention has been paid to the pertinence of the clinical indications for these products. The use of blood, and of erythrocytes in particular, has declined by almost 40%, but the use of immunoglobulins (IG) tripled between 2004 and 2018, making it necessary to pay donors to obtain sufficient blood to meet the market demand for these products. We analyzed the reasons for this increase to unsustainable levels of use, by investigating (practice) guidelines, recommendations, Cochrane data analyses and systematic reviews for clinical indications for IG over time. We found no new evidence explaining the huge increase up to 2018 or the predicted 5-7% yearly annual increase until 2024. For some former evidence-based indications, biologics have largely replaced IG, but the administration of IG for doubtful indications (up to 40%) has not decreased in recent decades. The main development since 2004 is that IG use in Europe has become market-driven rather than evidence-guided. As transfusion specialists and blood therapists, we must raise the alarm that this situation is likely to continue in the absence of good clinical studies determining the place of IG alongside other treatments, and for as long as market profitability remains the dominant driving force. We discuss here approaches for reversing this trend and moving towards European self-sufficiency through non-remunerated voluntary blood donation.

Transfusion Thresholds for Adult Respiratory Extracorporeal Life Support: An Expert Consensus Document

Severe acute respiratory distress syndrome (ARDS) can complicate novel pandemic coronavirus disease (COVID-19). Extracorporeal life support (ECLS) represents the final possible rescue strategy. Variations in practice, combined with a paucity of rigourous guidelines, may complicate blood-product resource availability and allocation during a pandemic. We conducted a literature review around venovenous extracorporeal membrane oxygenation (VV-ECMO) transfusion practices for platelets, packed red blood cells, fresh frozen plasma, prothrombin complex concentrate, and antithrombin. Pertinent society guidelines were examined, and the practice of Canadian ECLS experts was sampled through an environmental scan. This paper represents a synthesis of these explorations, combined with input from the Canadian Cardiovascular Critical Care (CANCARE) Society, Canadian Society of Cardiac Surgeons, and the Canadian Critical Care Society. We offer a pragmatic guidance document for restrictive transfusion thresholds in nonbleeding patients on VV-ECMO, which may attenuate transfusion-related complications and simultaneously shield national blood product inventory from strain during pandemic-induced activation of the National Plan for the Management of Shortages of Labile Blood Components.

Transfusion-transmitted cytomegalovirus: behaviour of cell-free virus during blood component processing. A study on the safety of labile blood components in Switzerland.

Nowadays, most blood products are leukocyte-reduced. After this procedure, the residual risk for transfusion transmitted cytomegalovirus (TT-CMV) is mostly attributed to cell-free viruses in the plasma of blood donors following primary infection or viral reactivation. Here, objectives are: 1) to study the behaviour of cell-free CMV through the blood component processing; 2) to determine the anti-CMV seroprevalence, the level of viremia, the window-period in blood donor population; and 3) to identify cases of TT-CMV in bone marrow transplant (BMT) recipients. Cell-free CMV was injected into blood bags originating from regular donors. Blood components were processed according to either the CompoSelect® or the CompoFlow® (Fresenius Kabi AG) techniques. Samples were analysed at each step for presence of virus DNA using quantitative polymerase chain reaction (PCR). The anti-CMV seroprevalence in our donor population was taken from our donor data system. The viremia was assessed in pooled plasmas samples from routine donations by quantitative PCR. Medical charts of 165 BMT anti-CMV seronegative recipients/anti-CMV seronegative donors who received CMV-unscreened blood products were reviewed. Cell-free CMV passes without any decrease in viral load through all stages of blood processing. The anti-CMV seroprevalence was 46.13%. Four DNA positive samples out of 42,240 individual blood donations were identified (0.009%); all had low levels of viremia (range 11-255 IU/mL). No window-period donation was identified. No TT-CMV was found. Cell-free CMV remains a concern with current blood component processing as it passes through all the processes. However, since low levels of CMV DNA were identified in the donations tested, and no BMT recipients had TT-CMV, the residual threat of TT-CMV after leukocyte reduction appears to be very low.

How to reduce rapidly destruction of labile blood components at the health facilities level? The experience of Centre Hospitalier de la Côte Basque

The destruction of labile blood components (LBC) is of major concern. The objective was to carry out actions aiming to rapidly reduce this rate and to evaluate results in a single institution. From 2017 we developed in the Centre Hospitalier de la Côte Basque a strategy in order to struggle against this problem including: 1/general information of prescriptors for reducing LBC waste, 2/fractioned delivery of RBC unit per unit, 3/recommendations to nurses, 4/information on platelets reserve, 5/new policy for ambulances and emergency unit: transfusion emergency package conditioned in single RBC units including a temperature recorder. Following the implementation of these measures, we analyzed the evolution of waste regarding number and distribution of causes. In contrast to stability of LBC destructions during these recent years between 0.84 and 0.97% we observed a marked decrease in 2017 (0.56%) and the first six months of 2018 (0.28%). Considering the evolution of causes between 2016 and 2017 we noticed for instance a disappearance of destructions due to patient' refusal and out of time of expiry or at level of the mobile emergency unit. Of note reduction of destruction is marked in the three categories of LBC. However, there still remains a large room for improvement regarding avoidable causes of destruction. It is possible to reduce very rapidly and significantly the fraction of LBC destruction in a health facility thanks to measures including information, teaching, organization and material conducted both in the blood bank and in clinical departments.

The organization of transfusion and fractionation in France and its regulation

Transfusion and plasma fractionation in France are closely linked to the historical reliance on voluntary unpaid blood donation that constitutes the foundation in the national system for the supply of labile blood components and stable fractionated plasma products. From 1993, three successive laws on safety of blood and medicines have been implemented to separate the missions of the stakeholders leading to clearly distinguish the mission of producers and regulatory bodies: operator for the blood sector, Etablissement Francais du Sang (EFS), operator for the fractionation into medicines, Laboratoire francais du Fractionnement et des Biotechnologies (LFB), and the regulator, the French National Agency for the Safety of Medicines and Health Products (ANSM). LFB has received the mandate of manufacturing fractionated plasma products from the plasma collected by EFS and to serve as a priority the needs of French patients. Since 1989, the European Union has built the regulatory framework for stable products, which are considered as medicinal products derived from human blood or human plasma. Many European legal and regulatory organisations supervise quality, biological safety, clinical safety, and efficacy of both blood components and medicinal products derived from human plasma. Guidelines, monographs, good practices (GXP or blood good practices) and others regulatory documents prompt operators to comply with these requirements, whereas operators, by improving their manufacturing practices, lead the regulation to adapt to innovation. France addresses these requirements in many legal and regulatory texts, most transposed from European legislation. While the two sectors are regulated in France by one unique national competent authority, the European Medicines Agency (EMA) does not include blood and blood components regulation under its responsibility. The safety and protection of donors is still carried out by the collegial cooperation of European and international operators. The European Commission has started to reflect on substances for human origin regulations as a whole, and a revision of the blood directive might lead to adapted definitions of voluntary, non-remunerated blood donations [including for plasma for fractionation (PfF)] in order to further protect the human body and its parts and to promote appropriate supply of European plasma.

Analyse des causes de destruction des produits sanguins labiles dans les établissements de santé : une étude multicentrique

ObjectiveOne of the tasks of haemovigilance correspondents in Health Institutions (HI) is to reduce the destruction of labile blood components (LBC). The objective of this study was to analyse in depth, five years after a first multicentric study, the causes of LBC destruction in order to assess the impact of measures taken and to define new ways of improvement. MethodsProspective analysis was carried out throughout 2016. For every LBC destroyed, the following elements were reported: type of LBC, transfusion department, cause of destruction analysed according to a decision tree, subsequently classed as avoidable or unavoidable. ResultsThe study included 15 HI. A total 3058 LBC were destroyed, representing an average 0.90% of issued LBC, and this analysis concerned 2576 LBC. Sixty-seven percent of LBC were issued for surgery, intensive care or emergencies. Forty percent of the causes of destruction were patient-related (death, clinical worsening, adverse effects or abnormal constants prior to delivery). Thirty percent were prescription-related, mainly cases of excessive prescription for different reasons. Eleven percent were linked to organisational issues. The rate of destruction judged avoidable, all causes combined, was 36%. ConclusionComparison with the precedent study shows improvement, thus revealing the efficacy of implemented measures (single-dose distribution, return procedures back to the site of distribution, training of participants). In order to further reduce this rate of destruction, we suggest to promote storage procedures and, above all, to continue to raise awareness within healthcare teams.

Blood and Blood Components: From Similarities to Differences.

Blood transfusion is made possible because, in most countries and organizations, altruistic individuals voluntarily, anonymously, and generously donate (without compensation) either whole blood or separated components that are then processed and distributed by professionals, prior to being allocated to recipients in need. Being part of modern medicine, blood transfusion uses so-called standard blood components when relative to cellular fractions and fresh plasma. However, as will be discussed in this paper, strictly speaking, such so-called labile blood components are not completely standard. Furthermore, the prevalent system based on voluntary, non-remunerated blood donation is not yet universal and, despite claims by the World Health Organization that 100% of blood collection will be derived from altruistic donations by 2020 (postponed to 2025), many obstacles may hinder this ambition, especially when relative to the collection of the enormous amount of plasma destined for fractionation into plasma derivative or drugs. Finally, country organizations also vary due to the economy, sociology, politics, and epidemiology. This paper then, discusses the particulars (of which ethical considerations) of blood transfusion diversity and the consequences for donors, patients, and society.

Pathogen Inactivation of Cellular Blood Products-An Additional Safety Layer in Transfusion Medicine.

In line with current microbial risk reduction efforts, pathogen inactivation (PI) technologies for blood components promise to reduce the residual risk of known and emerging infectious agents. The implementation of PI of labile blood components is slowly but steadily increasing. This review discusses the relevance of PI for the field of transfusion medicine and describes the available and emerging PI technologies that can be used to treat cellular blood products such as platelet and red blood cell units. In collaboration with the French medical device manufacturer Macopharma, the German Red Cross Blood Services developed a new UVC light-based PI method for platelet units, which is currently being investigated in clinical trials.

Pathogen reduction through additive-free short-wave UV light irradiation retains the optimal efficacy of human platelet lysate for the expansion of human bone marrow mesenchymal stem cells

BackgroundWe recently developed and characterized a standardized and clinical grade human Platelet Lysate (hPL) that constitutes an advantageous substitute for fetal bovine serum (FBS) for human mesenchymal stem cell (hMSC) expansion required in cell therapy procedures, avoiding xenogenic risks (virological and immunological) and ethical issues. Because of the progressive use of pathogen-reduced (PR) labile blood components, and the requirement of ensuring the viral safety of raw materials for cell therapy products, we evaluated the impact of the novel procedure known as THERAFLEX UV-Platelets for pathogen reduction on hPL quality (growth factors content) and efficacy (as a medium supplement for hMSC expansion). This technology is based on short-wave ultraviolet light (UV-C) that induces non-reversible damages in DNA and RNA of pathogens while preserving protein structures and functions, and has the main advantage of not needing the addition of any photosensitizing additives (that might secondarily interfere with hMSCs).Methodology / Principal findingsWe applied the THERAFLEX UV-Platelets procedure on fresh platelet concentrates (PCs) suspended in platelet additive solution and prepared hPL from these treated PCs. We compared the quality and efficacy of PR-hPL with the corresponding non-PR ones. We found no impact on the content of five cytokines tested (EGF, bFGF, PDGF-AB, VEGF and IGF-1) but a significant decrease in TGF-ß1 (-21%, n = 11, p<0.01). We performed large-scale culture of hMSCs from bone marrow (BM) during three passages and showed that hPL or PR-hPL at 8% triggered comparable BM-hMSC proliferation as FBS at 10% plus bFGF. Moreover, after proliferation of hMSCs in an hPL- or PR-hPL-containing medium, their profile of membrane marker expression, their clonogenic potential and immunosuppressive properties were maintained, in comparison with BM-hMSCs cultured under FBS conditions. The potential to differentiate towards the adipogenic and osteogenic lineages of hMSCs cultured in parallel in the three conditions also remained identical.Conclusion / SignificanceWe demonstrated the feasibility of using UV-C-treated platelets to subsequently obtain pathogen-reduced hPL, while preserving its optimal quality and efficacy for hMSC expansion in cell therapy applications.

Mass casualty events: blood transfusion emergency preparedness across the continuum of care.

Transfusion support is a key enabler to the response to mass casualty events (MCEs). Transfusion demand and capability planning should be an integrated part of the medical planning process for emergency system preparedness. Historical reviews have recently supported demand planning for MCEs and mass gatherings; however, computer modeling offers greater insights for resource management. The challenge remains balancing demand and supply especially the demand for universal components such as group O red blood cells. The current prehospital and hospital capability has benefited from investment in the management of massive hemorrhage. The management of massive hemorrhage should address both hemorrhage control and hemostatic support. Labile blood components cannot be stockpiled and a large surge in demand is a challenge for transfusion providers. The use of blood components may need to be triaged and demand managed. Two contrasting models of transfusion planning for MCEs are described. Both illustrate an integrated approach to preparedness where blood transfusion services work closely with health care providers and the donor community. Preparedness includes appropriate stock management and resupply from other centers. However, the introduction of alternative transfusion products, transfusion triage, and the greater use of an emergency donor panel to provide whole blood may permit greater resilience.

Re‐evaluating the residual risk of transfusion‐transmitted Ross River virus infection

Ross River virus (RRV) is an enveloped, RNA alphavirus in the same antigenic group as chikungunya virus. Australia records an annual average of 5000 laboratory-confirmed RRV infections. While RRV is currently geographically restricted to the Western Pacific, the capacity of arboviruses for rapid expansion is well established. The first case of RRV transfusion-transmission was recently described prompting a comprehensive risk assessment. To estimate the RRV residual risk, we applied laboratory-confirmed RRV notifications to two published models. This modelling generated point estimates for the risk of viraemia in the donor population, the risk of collecting a viraemic donation and the predicted number of infected components. The EUFRAT model estimated the risk of infection in donors as one in 95 039 (one in 311 328 to one in 32 399) to one in 14 943 (one in 48 593 to one in 5094). The point estimate for collecting a RRV viraemic donation varied from one in 166 486 (one in 659 078 to one in 49 158) (annualized national risk) to one in 26 117 (one in 103 628 to one in 7729) (area of high transmission). The modelling predicted 8-11 RRV-infected labile blood components issued in Australia during a 1-year period. Considering the uncertainty in the modelled estimates, the unknown rate of RRV donor viraemia and the low severity of any recipient RRV infection, additional risk management for RRV in Australia will initially be restricted to strengthening the messaging to donors regarding prompt reporting of any postdonation illnesses.

Improving platelet transfusion safety: biomedical and technical considerations.

Platelet concentrates account for near 10% of all labile blood components but are responsible for more than 25% of the reported adverse events. Besides factors related to patients themselves, who may be particularly at risk of side effects because of their underlying illness, there are aspects of platelet collection and storage that predispose to adverse events. Platelets for transfusion are strongly activated by collection through disposal equipment, which can stress the cells, and by preservation at 22 °C with rotation or rocking, which likewise leads to platelet activation, perhaps more so than storage at 4 °C. Lastly, platelets constitutively possess a very large number of bioactive components that may elicit pro-inflammatory reactions when infused into a patient. This review aims to describe approaches that may be crucial to minimising side effects while optimising safety and quality. We suggest that platelet transfusion is complex, in part because of the complexity of the "material" itself: platelets are highly versatile cells and the transfusion process adds a myriad of variables that present many challenges for preserving basal platelet function and preventing dysfunctional activation of the platelets. The review also presents information showing--after years of exhaustive haemovigilance--that whole blood buffy coat pooled platelet components are extremely safe compared to the gold standard (i.e. apheresis platelet components), both in terms of acquired infections and of immunological/inflammatory hazards.

Quality indicators for the hospital transfusion chain: a national survey conducted in 100 dutch hospitals.

The 2011 Dutch Blood Transfusion Guideline for hospitals incorporates seven internal quality indicators for evaluation of the hospital transfusion chain. The indicators aim to measure guideline compliance as shown by the instatement of a hospital transfusion committee and transfusion safety officer (structural indicators), observance of transfusion triggers and mandatory traceability of labile blood components (process indicators). Two voluntary online surveys were sent to all Dutch hospitals for operational years 2011 and 2012 to assess compliance with the guideline recommendations. Most hospitals had a hospital transfusion committee and had appointed a transfusion safety officer (TSO). In 2012, only 23% of hospitals complied with the recommended minimum of four annual transfusion committee meetings and 8 h/week for the TSO. Compliance with the recommended pretransfusion haemoglobin threshold for RBC transfusion was achieved by 90% of hospitals in over 80% of transfusions; 58% of hospitals measured the pretransfusion platelet count in over 80% of platelet transfusions and 87% of hospitals complied with the legally mandatory traceability of blood components in over 95% of transfusions. With the current blood transfusion indicators, it is feasible to monitor aspects of the quality of the hospital transfusion chain and blood transfusion practice and to assess guideline compliance. The results from this study suggest that there are opportunities for significant improvement in blood transfusion practice in the Netherlands. These indicators could potentially be used for national and international benchmarking of blood transfusion practice.

Pathogen reduction technologies

BackgroundIdeally, pathogen reduction technology (PRT) should provide proactive protection against emerging pathogens, reduce the need to introduce additional testing, minimize bacterial contamination and potentially replace processing steps such as gamma‐irradiation.Material and MethodsAvailable literature regarding technologies currently in use or under development for the treatment of labile blood components during processing was reviewed.ResultsThe INTERCEPT and Mirasol PRT systems are used widely in blood centres in Europe, Asia and the Middle East for the treatment of both platelets and plasma, whereas clinical trials of platelets treated using the THERAFLEX UV‐Platelets system are underway. In vitro data suggest that PRT treatment leads to some loss of platelet function. However, haemovigilance reports from countries where PRT‐treated platelets and plasma are transfused indicate no change in component usage, and indeed a reduction in transfusion‐related adverse events. Animal models are being used to elucidate mechanisms for these observed reductions. A second‐generation S‐303 system for red cells is also under development, as is a Mirasol PRT system for treatment of whole blood. Preliminary data indicate that these technologies may eventually become available.ConclusionThe challenge for blood services is to understand and rationalize the costs, risks and benefits of PRT compared with removing any tests or processes, whilst aiming to provide the highest level of blood safety. Ongoing post‐marketing surveillance and clinical trials are still required for all PRT systems.

Les différents types de plasmas thérapeutiques sont-ils équivalents ?

In France, three varieties of therapeutic plasma are being processed, distributed and delivered, currently; however, many more varieties are in use worldwide, which go by the property of labile blood component or plasma derived medicines. For one type of component (one given name), several devices and bags and so on are used to concur to its process, which makes that one type of therapeutic plasma may significantly differ from one production setting to one other. This may affect (more or less) the component properties as well as the possibly reported adverse events. This review aims thus, firstly at stressing on the difficulty in comparing data obtained in different contexts, and secondly at making the point on future directions to process therapeutic plasma.

Plasma Treated with Methylene Blue and Light: Clinical Efficacy and Safety Profile

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

Sustainability of a public system for plasma collection, contract fractionation and plasma-derived medicinal product manufacturing.

In Italy, the financial reimbursement for labile blood components exchanged between Regions is regulated by national tariffs defined in 1991 and updated in 1993-2003. Over the last five years, the need for establishing standard costs of healthcare services has arisen critically. In this perspective, the present study is aimed at defining both the costs of production of blood components and the related prices, as well as the prices of plasma-derived medicinal products obtained by national plasma, to be used for interregional financial reimbursement. In order to analyse the costs of production of blood components, 12 out 318 blood establishments were selected in 8 Italian Regions. For each step of the production process, driving costs were identified and production costs were. To define the costs of plasma-derived medicinal products obtained by national plasma, industrial costs currently sustained by National Health Service for contract fractionation were taken into account. The production costs of plasma-derived medicinal products obtained from national plasma showed a huge variability among blood establishments, which was much lower after standardization. The new suggested plasma tariffs were quite similar to those currently in force. Comparing the overall costs theoretically sustained by the National Health Service for plasma-derived medicinal products obtained from national plasma to current commercial costs, demonstrates that the national blood system could gain a 10% cost saving if it were able to produce plasma for fractionation within the standard costs defined in this study. Achieving national self-sufficiency through the production of plasma-derived medicinal products from national plasma, is a strategic goal of the National Health Service which must comply not only with quality, safety and availability requirements but also with the increasingly pressing need for economic sustainability.

Immune‐reactive soluble OX40 ligand, soluble CD40 ligand, and interleukin‐27 are simultaneously oversecreted in platelet components associated with acute transfusion reactions

Leukoreduction of labile blood components dramatically decreases the frequency of minor, intermediate, and severe adverse events (AEs), referred to as acute transfusion reactions (ATRs), especially after transfusion of platelet components (PCs). The pathophysiology of AEs may result from accumulation of soluble, secreted, platelet (PLT) factors with proinflammatory functions stored in PCs. Thus, several cosynergizing factors associated with PLT accumulation in PCs may contribute to clinically reported ATRs with inflammatory symptoms. We screened for 65 PLT-associated secretory products in PCs that caused ATRs and identified PLT molecules associated with ATRs and inflammation. A functional in vitro study using PC supernatants assayed on reporting immune cells was performed to indicate relevance. Among 10,600 apheresis PCs, 30 caused inflammatory ATRs and contained significantly elevated levels of soluble CD40 ligand (sCD40L), interleukin (IL)-27, and soluble OX40 ligand (sOX40L). Normal PLTs secreted IL-27 and sOX40L at bioactive concentrations upon thrombin stimulation and were up regulated in association with ATRs, similar to sCD40L. Other secreted products were identified but not investigated further as their positivity was not consistent. This study demonstrates the putative participation of PLT-derived sOX40L, IL-27, and sCD40L, which accumulate in PC supernatants, with inflammatory-type ATRs. Further studies are required to determine the clinical significance of these findings to forecast preventive measures whenever possible.