Implementation of amotosalen plus ultraviolet A-mediated pathogen reduction for all platelet concentrates in France: Impact on the risk of transfusion-transmitted infections.

BACKGROUND AND OBJECTIVES: Pathogen reduction (PR) technology may reduce the risk of transfusion-transmitted infections (TTIs), notably transfusion-transmitted bacterial infection (TTBI) associated with platelet concentrates (PCs). PR (amotosalen/UVA treatment) was implemented for all PCs transfused in France in November 2017. No bacterial detection was in place beforehand. The study aimed to assess the impact of PR PC on TTI and TTBI near-miss occurrences. MATERIALS AND METHODS: TTI and TTBI near-miss occurrences were compared before and after 100% PR implementation. The study period ran from 2013 to 2022. Over 300,000 PCs were transfused yearly. RESULTS: No PC-related transmission of human immunodeficiency virus, hepatitis C virus, hepatitis B virus and human T-cell lymphotropic virus was reported throughout the study period. PC-mediated hepatitis E virus and hepatitis A virus infections occurred irrespective of PR implementation. Mean PC-mediated TTBI occurrence before PR-PC implementation was 3/year (SD: 1; n = 15; 1/92,687 PC between 2013 and 2016) with a fatal outcome in two patients. Since PR implementation, one TTBI has been reported (day 4 PC, Bacillus cereus) (1/1,645,295 PC between 2018 and 2022; p < 0.001). Two PR PC quarantined because of a negative swirling test harboured bacteria: a day 6 PC in 2021 (B. cereus and Staphylococcus epidermidis) and a day 7 PC in 2022 (Staphylococcus aureus). Five similar occurrences with untreated PC were reported between 2013 and 2020. CONCLUSION: Transfusion of 100% PR PC resulted in a steep reduction in TTBI occurrence. TTBI may, however, still occur. Pathogen-reduced PC-related TTI involving non-enveloped viruses occurs as well.

Hypersensitivity transfusion reactions to platelet concentrate: a retrospective analysis of the French hemovigilance network.

BACKGROUND: Among labile blood products, platelet concentrates (PCs) are the leading cause of hypersensitivity transfusion reactions (HTRs). These reactions often lead to interruption of PC transfusion and can result in a prolonged transfusion process leading to significant morbidity and use of premedication and close monitoring for patients with a history of allergic transfusion reactions. The French hemovigilance database is one of the largest standardized databases providing information on HTRs following administration of labile blood products. In this study, we analyzed this database to assess the relative risk of HTR for each type of PC. STUDY DESIGN AND METHODS: HTRs following PC transfusion were retrospectively extracted from the e-Fit Hemovigilance database of the French National Agency for Medicines and Health Products Safety (ANSM). Frequencies were calculated using the number of specific PCs transfused. RESULTS: Between 2008 and 2014, the overall estimated incidence of HTRs following PC administration was calculated at 232 HTRs per 100,000 PCs transfused. The rate of HTRs was significantly higher with apheresis PC (337/100,000) than with buffy-coat PC (94/100,000). Platelets in additive solutions (PAS) were associated with a significantly lower frequency of HTRs when compared with PCs in native plasma. Amotosalen/UVA- PCs (APCs and BCPCs) which are always in PAS in France, exhibited the lowest frequency of HTRs when compared with their corresponding PCs in native plasma or in PAS (p < 10-7 in all comparisons). CONCLUSION: Our results showed that the type of PC and its processing may have an impact on the risk of HTR.

West Nile and Usutu Virus Infections and Challenges to Blood Safety in the European Union.

West Nile virus (WNV) and Usutu virus (USUV) circulate in several European Union (EU) countries. The risk of transfusion-transmitted West Nile virus (TT-WNV) has been recognized, and preventive blood safety measures have been implemented. We summarized the applied interventions in the EU countries and assessed the safety of the blood supply by compiling data on WNV positivity among blood donors and on reported TT-WNV cases. The paucity of reported TT-WNV infections and the screening results suggest that blood safety interventions are effective. However, limited circulation of WNV in the EU and presumed underrecognition or underreporting of TT-WNV cases contribute to the present situation. Because of cross-reactivity between genetically related flaviviruses in the automated nucleic acid test systems, USUV-positive blood donations are found during routine WNV screening. The clinical relevance of USUV infection in humans and the risk of USUV to blood safety are unknown.

Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting.

Pathogen reduction (PR) of selected blood components is a technology that has been adopted in practice in various ways. Although they offer great advantages in improving the safety of the blood supply, these technologies have limitations which hinder their broader use, e.g. increased costs. In this context, the European Centre for Disease Prevention and Control (ECDC), in co-operation with the Italian National Blood Centre, organised an expert consultation meeting to discuss the potential role of pathogen reduction technologies (PRT) as a blood safety intervention during outbreaks of infectious diseases for which (in most cases) laboratory screening of blood donations is not available. The meeting brought together 26 experts and representatives of national competent authorities for blood from thirteen European Union and European Economic Area (EU/EEA) Member States (MS), Switzerland, the World Health Organization, the European Directorate for the Quality of Medicines and Health Care of the Council of Europe, the US Food and Drug Administration, and the ECDC. During the meeting, the current use of PRTs in the EU/EEA MS and Switzerland was verified, with particular reference to emerging infectious diseases (see Appendix). In this article, we also present expert discussions and a common view on the potential use of PRT as a part of both preparedness and response to threats posed to blood safety by outbreaks of infectious disease.

Analysis of Transfusion-Related Acute Lung Injury and Possible Transfusion-Related Acute Lung Injury Reported to the French Hemovigilance Network From 2007 to 2013.

Using the French Hemovigilance Network database from 2007 to 2013, we provide information on demographics, incidence, and risk factors of reported transfusion-related acute lung injury (TRALI) and possible TRALI, analyze TRALI mitigation efforts for fresh frozen plasma and platelet concentrates, and consider the impact of platelet additive solutions on TRALI incidence. We applied the Toronto consensus conference definitions for TRALI and possible TRALI. Two TRALI subgroups were considered: "antibody positive" when a donor has human leukocyte antigen (class I or II) and/or human neutrophil antigen antibodies and the recipient has cognate antigen, and "antibody negative" when immunological investigation is negative or not done. The analysis targeted 378 cases, divided into antibody-positive TRALI (n=75), antibody-negative TRALI (n=100), and possible TRALI (n=203). TRALI patients were younger and received more blood components than the general population of transfused patients. Moreover, we identified the following clinical conditions where patients seemed to be at higher risk to develop TRALI: postpartum hemorrhage, acute myeloid leukemia, liver transplantation, allogeneic and autologous hematopoietic stem cells transplantation, polytrauma, and thrombotic microangiopathy. Policy measures intended to reduce antibody-positive TRALI were found effective for apheresis platelet concentrates and fresh frozen plasma but not for whole blood-derived platelet concentrates. The use of platelet additive solutions was associated with a significant reduction in the incidence of TRALI following transfusion of buffy coat-derived platelet concentrates but not following transfusion of apheresis platelets. Our data reinforce the concept that possible TRALI and TRALI, as defined in the Canadian consensus conference, share many characteristics. No specific policy measures are currently directed at mitigation of possible TRALI despite its impact on transfusion safety. Despite TRALI mitigation measures, the overall incidence of TRALI cases reported to the French Hemovigilance system was not significantly reduced. Therefore, additional research is needed to reduce, if not eradicate, all TRALI categories.