Transfusion-transmitted Bacterial Infections Research Articles

Evaluation of bacterial safety approaches of platelet blood concentrates: bacterial screening and pathogen reduction.

This mini-review analyzed two approaches to screening bacterial contamination and utilizing pathogen reduction technology (PRT) for Platelet concentrates (PCs). While the culture-based method is still considered the gold standard for detecting bacterial contamination in PCs, efforts in the past two decades to minimize transfusion-transmitted bacterial infections (TTBIs) have been insufficient to eliminate this infectious threat. PRTs have emerged as a crucial tool to enhance safety and mitigate these risks. The evidence suggests that the screening strategy for bacterial contamination is more successful in ensuring PC quality, decreasing the necessity for frequent transfusions, and improving resistance to platelet transfusion. Alternatively, the PRT approach is superior regarding PC safety. However, both methods are equally effective in managing bleeding. In conclusion, PRT can become a more prevalent means of safety for PCs compared to culture-based approaches and will soon comprehensively surpass culture-based bacterial contamination detection methods.

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

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. 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. 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. 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.

Safety Analysis of Extended Platelet Shelf-Life with Large-Volume Delayed Sampling on BACT/ALERT® VIRTUO® in Australia.

Transfusion-transmitted bacterial infection (TTBI) is the leading cause of transfusion-transmitted infections. Platelet components are more likely to be associated with bacterial contamination due to their storage requirements. Australian Red Cross Lifeblood introduced the bacterial contamination screening (BCS) of all platelet components in 2008. The process was recently updated with the use of BACT/ALERT® VIRTUO®, a large-volume delayed sampling (LVDS) protocol and extending platelet shelf-life to seven days. This article describes the results from the routine BCS of platelet components in Australia. Use of VIRTUO has resulted in lower false-positive rates, reducing wastage and improving platelet inventory. Our findings show that the combination of LVDS and VIRTUO improves the safety of platelet transfusions through earlier time to detection, especially for pathogenic bacterial species. Pathogenic bacteria grew within 24 h of incubation with a clear delineation between pathogenic and non-pathogenic species. The data show this protocol is very safe, with no TTBI cases during this time. There were no TTBI reports in recipients of platelet components that subsequently had a positive culture with Cutibacterium species, probably due to the low pathogenic potential of these organisms and slow replication in aerobic platelet bags. We conclude there is no advantage in incubating culture bottles beyond five days.

Two cases of Streptococcus dysgalactiae subspecies equisimilis infection transmitted through transfusion of platelet concentrate derived from separate blood donations by the same donor.

Transfusion-transmitted bacterial infections (TTBIs) in Japan have been largely prevented due to a short shelf life of 3.5 days after blood collection for platelet concentrate (PC) and washed PCs (WPCs; PC in which 95% plasma is replaced by platelet additive solution). Case 1: In January 2018, a woman in her 50s with aplastic anaemia who received WPC transfusion and developed a fever the next day and Streptococcus dysgalactiae subspecies equisimilis (SDSE) was detected in the residual WPC. Case 2: In May 2018, a man in his 60s with a haematologic malignancy who received PC transfusion and developed chills during the transfusion. SDSE was detected in the patient's blood and residual PC. The contaminated platelet products were both manufactured from blood donated by the same donor. The multi-locus sequencing typing revealed that SDSE detected in case 1 was identical to that from case 2; however, whole blood subsequently obtained from the donor was culture negative. WPC and PC produced from two blood donated 106 days apart by the same donor were contaminated with SDSE of the same strain and both caused TTBIs. Safety measures should be considered regarding blood collection from a donor with a history of bacterial contamination.

Longitudinal analysis of annual national hemovigilance data to assess pathogen reduced platelet transfusion trends during conversion to routine universal clinical use and 7-day storage.

France converted to universal pathogen reduced (PR; amotosalen/UVA) platelets in 2017 and extended platelet component (PC) shelf-life from 5- to 7-days in 2018and2019. Annual national hemovigilance (HV) reports characterized longitudinal PC utilization and safety over 11 years, including several years prior to PR adoption as the national standard of care. Data were extracted from published annual HV reports. Apheresis and pooled buffy coat [BC] PC use was compared. Transfusion reactions (TRs) were stratified by type, severity, and causality. Trends were assessed for three periods: Baseline (2010-14; ~7% PR), Period 1 ([P1] 2015-17; 8%-21% PR), and Period 2 ([P2] 2018-20; 100% PR). PC use increased by 19.1% between 2010 and 2020. Pooled BC PC production increased from 38.8% to 68.2% of total PCs. Annual changes in PCs issued averaged 2.4% per year at baseline, -0.02% (P1) and 2.8% (P2). The increase in P2 coincided with a reduction in the target platelet dose and extension to 7-day storage. Allergic reactions, alloimmunization, febrile non-hemolytic TRs, immunologic incompatibility, and ineffective transfusions accounted for >90% of TRs. Overall, TR incidence per 100,000 PCs issued declined from 527.9 (2010) to 345.7 (2020). Severe TR rates declined 34.8% between P1-P2. Forty-six transfusion-transmitted bacterial infections (TTBI) were associated with conventional PCs during baseline and P1. No TTBI were associated with amotosalen/UVA PCs. Infections with Hepatitis E (HEV) a non-enveloped virus resistant to PR, were reported in all periods. Longitudinal HV analysis demonstrated stable PC utilization trends with reduced patient risk during conversion to universal 7-day amotosalen/UVA PCs.

Analysis of Transfusion-Transmitted Bacterial Infections according to German Hemovigilance Data (2011–2020)

Introduction: Following the first assessment of the effects of safety measures taken against transfusion-transmitted bacterial infections (TTBI), the Paul-Ehrlich-Institut (PEI) decided to newly analyze risk minimization measures (RMM) using German hemovigilance data from 2011 to 2020, focusing on blood components, recipients, and bacterial strains. Materials and Methods: The PEI assessed the imputability of all reported serious adverse reactions (SAR) relying mainly on microbiological test results. Reporting rates (RR) of suspected, confirmed, and fatal confirmed TTBI were calculated and compared to the previous reporting 10-year period (2001–2010) using Poisson regression to estimate RR ratios (RRR). Furthermore, details on blood component age, patients’ medical history, and bacterial pathogenicity were collected. Results: With respect to the previous 10-year period, the number of suspected TTBI increased (n = 403), while fewer cases were confirmed (n = 40); the number of deaths remained more or less unchanged (n = 8). The RR for suspected TTBI were 7.9, 18.7, and 1.6 cases per million units transfused for red blood cells (RBC), platelet concentrates (PC), and fresh frozen plasma (FFP), respectively. RRR showed a statistically significant 2.5-fold increase in the RR for suspected TTBI after RBC administration from 2001–2010 to the period under review (p < 0.0001). The RR for confirmed TTBI were 0.4, 5.0, and 0.0 cases per million units transfused for RBC, PC, and FFP, respectively. Compared to the period 2001–2010, there was a statistically significant decrease in the RR of confirmed TTBI by half for PC (p = 0.0052). The RR for confirmed PC-caused TTBI with fatal outcome was 1.4 cases per million units transfused. Regardless of type of blood product transfused and outcome of SAR, the majority of TTBI occurred after administration of a product at the end of shelf life (40.0%) and to recipients of advanced age (median age: 68.5 years) and/or with severe immunosuppression (72.5%) due to decreased myelopoiesis (62.5%). 72.5% of the involved bacteria had a middle/high human pathogenicity. Conclusion: Despite a significant decrease in confirmed TTBI following PC transfusion in Germany after implementation of RMM, the current manufacture of blood products can still not prevent TTBI with fatal outcomes. As demonstrated in various countries, RMM like bacterial screening or pathogen reduction may measurably improve the safety of blood transfusion.

Transfusion transmitted bacterial infections (TTBI) involving contaminated platelet concentrates: residual risk despite intervention strategies

Background: Transfusion transmitted bacterial infection (TTBI) due to contamination of platelets is an important risk of blood transfusion. Our strategies to decrease bacterial contamination include skin disinfection, diversion of the first blood flow, and bacterial screening. Despite these intervention strategies, a residual risk remains.

Current status of rapid bacterial detection methods for platelet components: A 20-year review by the ISBT Transfusion-Transmitted Infectious Diseases Working Party Subgroup on Bacteria.

Bacterial contamination of platelet components (PCs) poses a safety challenge for transfusion patients. Despite mitigation interventions, the residual risk of transfusion-transmitted bacterial infections remains predominant. PC safety can be improved either by pathogen reduction or by implementation of bacterial detection methods. Detection methodologies include culture methods and rapid detection methods. The current review focuses on currently available rapid detection methods. We reviewed published manuscripts since 2000 on rapid bacterial detection methods used for PC screening with result determination within 4 h. Methods meeting this criterion included Verax PGDprime, BacTx and nucleic amplification testing. The analytical and diagnostic sensitivity and specificity of these systems were assessed. The analytical sensitivity between the different detection methods ranged between 50 and 100,000 CFU/ml. The sample volume used by these testing systems varies between 0.5 and 1.0ml of PCs. A delay of at least 48 h before sampling enhances detectability. All rapid detection methods generate results in a timely manner, allowing testing to be performed before transfusion with optimal sensitivity. Rapid detection methods improve PC safety regarding bacterial contamination. The assays are optimal for rapidly growing bacteria, which are more likely to cause septic transfusion reactions in patients. Because of the reduced diagnostic sensitivity, the sample collection should be late in shelf-life and ideally just before transfusion. The major benefit of these methods is that the test result can be obtained before releasing PCs for transfusion or to be used in combination with other screening methods applied early during PC storage.

Residual risks of bacterial contamination for pathogen-reduced platelet components.

Platelet components are commonly transfused to patients for a variety of indications, including patients with low platelet counts or patients with platelet dysfunction who are bleeding or at high risk of bleeding. Although the risk of pathogen contamination of platelet components has declined significantly over the last 40 years, it remains a concern for the patients, for blood banks and for physicians. Pathogen inactivation (PI) technologies have been developed to mitigate this risk. This review focuses on the residual risks of transfusion-transmitted bacterial infections by platelet transfusion after PI. We describe and assess the relationship between the bacterial load and the timing and capacity of reduction of the different PI technologies, as well as the risks that could represent spore-forming microorganisms and the possible introduction of microorganisms after PI.

The international experience of bacterial screen testing of platelet components with automated microbial detection systems: An update.

In 2014, the bacterial subgroup of the Transfusion-Transmitted Infectious Diseases working party of ISBT published a review on the International Experience of Bacterial Screen Testing of Platelet Components (PCs) with an Automated Microbial Detection System. The purpose of this review, which is focused on publications on or after 2014, is to summarize recent experiences related to bacterial contamination of PCs and the use of an automated culture method to safeguard the blood supply. We first reviewed septic transfusion reactions after PC transfusion as reported in national haemovigilance systems along with a few reports from various countries on bacterial contamination of blood products. Next, we reviewed PC automated culture protocols employed by national blood services in the United Kingdom, Australia, Canada and large blood collection organization and hospital transfusion services in the United States. Then, we acknowledged the limitations of currently available culture methodologies in abating the risks of transfusion-transmitted bacterial infection, through a review of case reports. This review was neither meant to be critical of the literature reviewed nor meant to identify or recommend a best practice. We concluded that significant risk reduction can be achieved by one or a combination of more than one strategy. No one approach is feasible for all institutions worldwide. In selecting strategies, institutions should consider the possible impact on platelet components availability and entertain a risk-based decision-making approach that accounts for operational, logistical and financial factors.

Changes in the incidence of transfusion reactions in hematological patients over the past 30 years.

Patients with hematological diseases are polytransfused and often immunocompromised, therefore susceptible to transfusion reactions (TR). This study aims to document the incidence of TRs in adult hematological patients and assess the effect of changes in the production of blood components and transfusion practice on their occurrence. Retrospective observational analysis of TRs reported from 1993 to 2019 was performed. For the analysis of the effect of changes on the incidence of TRs, the evaluated time was divided into two periods: the 1st period before the introduction of changes in production, when leukoreduced blood components were used only selectively, and the 2nd period, when semi-automated method of production and universal leukoreduction was introduced. The decrease in the incidence of TRs was observed for both red blood cell (RBC) and platelet concentrate (PC) transfusions in the 2nd period. Since platelet additive solution has been used, a further decrease in the incidence was reported. The decrease in incidence was also observed for delayed hemolytic/serological transfusion reactions and for transfusion-transmitted bacterial infections. Four cases of incorrect blood transfusions were uniquely related to the hematological patients, caused by antigen loss and transfusion ordering after ABO-incompatible hematopoietic stem cell transplantation. Our results provided evidence that the introduction of tools offered by modern transfusion medicine: universal leukodepletion, plasma replacement with additive solutions, sensitive laboratory techniques, prophylactic antigen matching policy, informatization, and automatization, decreased the incidence of TRs and improved transfusion safety.

Mitigating the risk of transfusion-transmitted bacterial infections in hematology oncology patients.

e19047 Background: Hospital acquired infections create major logistical, financial, and patient safety concerns within the healthcare system. Bacterial contamination (BC) of platelet components (PCs) can lead to transfusion-transmitted bacterial infections (TTBI), central line-associated bloodstream infections, and sepsis, with long-term complications and/or death. In the US, hematopoietic stem cell transplant (HSCT) recipients require transfusion support until engraftment and together with hematology/oncology (hemonc.) patients receive the highest number of PCs/patient. FDA’s Guidance recommends approaches to reduce BC risk including the use of enhanced bacterial culture screening (EBSC) or pathogen reduction (PR) of platelets. Methods: The Miami Cancer Institute (MCI) implemented PR-PCs for all allogeneic HSCT patients. Irradiation, CMV testing, and bacterial screening have been discontinued for PR-PCs. Transfusion outcomes are being monitored using active hemovigilance (HV) reporting. Results: Considering the fatality risk associated with BC of PCs (1:200,000 – 1:1,000,000) despite the use of optimal skin cleansing, initial sample diversion, and primary bacterial culture, 1/2,880 PCs are still contaminated (Bloch et al.); further steps towards BC mitigation are needed. As the UK and US reported a residual BC risk of 5.4-9.4/million PCs after implementation of EBSC, PR may represent an alternative approach with other cumulative benefits. Indeed, national HV data from France, Switzerland and Belgium reported no sepsis transfusion reactions since PR implementation (Benjamin et al.). In addition, the risk of TA-GVHD and other TTI including emerging infectious diseases (EID) may be decreased after the inactivation of pathogens and leukocytes (Lanteri et al.). At MCI, the percentage of transfused PR-PCs has been increasing steadily from 7.9% in July 2019 to 22.2% in January 2021. Over a 19 month-period, a total of 9,296 PC were transfused including 1,677 PR-PCs. While non-PR-PCs were all irradiated and bacterially screened, PR-PC were neither irradiated nor bacterially screened. No cases of TA-GVHD or TTI were reported. A total of 27 mild, non-life-threatening platelet transfusion reactions were reported including 22 (81.5%) after non-PR PCs transfusion and 5 (18.5%) after PR-PC transfusion. In addition, the early release of transfusion-ready fresh PR-PCs 24-48 hours after collection has proven invaluable in providing clinicians and patients with blood continuity during the COVID-19 pandemic. Conclusions: Though certain measures have improved blood safety, the risk of TTI associated with PC transfusion remains a concern for vulnerable hemonc. patients. Using PR-PC is especially important to consider when patients undergo extensive life-saving therapies such as bone marrow transplants.

Platelet safety strategies in Japan: impact of short shelf life on the incidence of septic reactions

Transfusion-transmitted bacterial infections (TTBIs) often have serious consequences for patients. The Japanese Red Cross (JRC) has not implemented culture screening for platelet concentrate (PC), but it has maintained a shelf life of 85 hours for PC. The JRC collected reports of suspected TTBI and investigated causal relationships using PC samples and patient blood samples. PCs showing apparent abnormalities were retrieved and cultured and analyzed for bacterial growth. The JRC analyzed 86 samples available from 135 transfused PCs with suspected TTBIs that were collected over the past 12 years; 17 (19.8%) were culture-positive. One, 6, and 10 TTBIs developed in patients on Days 1, 2, and 3 after PC collection, respectively. Assuming that PC is transfused on the day of issue, the TTBI risk was fourfold higher on Day 3 than on Day 2, after adjusting the TTBI incidence for the number of PCs issued per day. Compared with the model of issuing all PCs on Day 3, issuing PCs with the current distribution of storage time could have decreased the TTBI incidence by 56%. During the past 8 years, the JRC retrieved 960 PC units because of apparent abnormalities, 2.8% of which were culture-positive. The short shelf life of PC is associated with a low incidence of reported TTBIs, more than half of which occurred on Day 3 relative to earlier time points. Visual inspection of PC before transfusion is crucial in detecting bacterially contaminated PC despite its low positive predictive value.

Genotypic study of Citrobacter koseri, an emergent platelet contaminant since 2012 in France.

Transfusion-transmitted bacterial infection is a rare occurrence but the most feared complication in transfusion practices. Between 2012 and 2017, five cases of platelet concentrates (PCs) contaminated with the bacterial pathogen Citrobacter koseri (PC-Ck) have been reported in France, with two leading to the death of the recipients. We tested the possibilities of the emergence of a PC-specific clone of C. koseri (Ck) and of specific bacterial genes associated with PC contamination. The phylogenetic network, based on a homemade Ck core genome scheme, inferred from the genomes of 20 worldwide Ck isolates unrelated to PC contamination taken as controls (U-Ck) and the genomes of the five PC-Ck, explored the clonal relationship between the genomes and evaluated the distribution of PC-Ck throughout the species. Along with this core genome multilocus sequence typing approach, a Ck pan genome has been used to seek genes specific to PC-Ck isolates. Our genomic approach suggested that the population of C. koseri is nonclonal, although it also identified a cluster containing three PC-Ck and eight U-Ck. Indeed, the PC-Ck did not share any specific genes. The elevated incidence of PCs contaminated by C. koseri in France between 2012 and 2017 was not due to the dissemination of a clone. The determinants of the recent outbreaks of PC contamination with C. koseri are still unknown.

Atypical Bacterial Growth within Units of Platelets Challenges Transfusion Medicine Dogma.

Although transfusion-transmitted bacterial infection is relatively rare, mitigation of bacterial contamination of platelet units is arguably the top current transfusion-related safety concern. Several different technologies have been employed to detect or neutralize bacteria in platelet concentrates. However, studies of the efficacy of these systems have been hampered by problematic definitions of what represents a "true-positive" versus a "false-positive" culture result. In the current issue of the Journal of Clinical Microbiology (M. Cloutier, M.-È. Nolin, H. Daoud, A. Jacques, M. J. de Grandmont, É Ducas, G. Delage, and L. Thibault, J Clin Microbiol 56:e01105-18, 2018, https://doi.org/10.1128/JCM.01105-18), it was demonstrated that the growth of Bordetella holmesii is inhibited by the platelet storage environment, which may explain why the results of initial positive platelet cultures are not always confirmed by subsequent cultures later during the storage period. This important finding is at odds with the generally held belief within the field of transfusion medicine that initially positive platelet cultures that are not confirmed on repeat testing are instrumentation-based false positives. The clinical risk profile of organisms demonstrating storage-related low viability is worthy of further study.

Combining culture and microbead‐based immunoassay for the early and generic detection of bacteria in platelet concentrates

Despite current preventive strategies, bacterial contamination of platelets is the highest residual infectious risk in transfusion. Bacteria can grow from an initial concentration of 0.03-0.3 colony-forming units (CFUs)/mL up to 108 to 109 CFUs/mL over the product shelf life. The aim of this study was to develop a cost-effective approach for an early, rapid, sensitive, and generic detection of bacteria in platelet concentrates. A large panel of bacteria involved in transfusion reactions, including clinical isolates and reference strains, was established. Sampling was performed 24 hours after platelet spiking. After an optimized culture step for increasing bacterial growth, a microbead-based immunoassay allowed the generic detection of bacteria. Antibody production and immunoassay development took place exclusively with bacteria spiked in fresh platelet concentrates to improve the specificity of the test. Antibodies for the generic detection of either gram-negative or gram-positive bacteria were selected for the microbead-based immunoassay. Our approach, combining the improved culture step with the immunoassay, allowed sensitive detection of 1 to 10 CFUs/mL for gram-negative and 1 to 102 CFUs/mL for gram-positive species. In this study, a new approach combining bacterial culture with immunoassay was developed for the generic and sensitive detection of bacteria in platelet concentrates. This efficient and easily automatable approach allows tested platelets to be used on Day 2 after collection and could represent an alternative strategy for reducing the risk of transfusion-transmitted bacterial infections. This strategy could be adapted for the detection of bacteria in other cellular products.

Genotypic and phenotypic characteristics of Escherichia coli involved in transfusion-transmitted bacterial infections: implications for preventive strategies.

Transfusion-transmitted bacterial infections (TTBIs) are the main residual infectious complications of transfusions. Escherichia coli and platelet (PLT) concentrates may be epidemiologically associated, leading to severe, if not lethal, TTBIs. We investigated the genotypic and phenotypic reasons for this clinically deleterious combination. We investigated a French national E. coli strain collection related to six independent episodes of TTBIs. Their phenotypic characterizations included antibiotic susceptibility testing, growth testing under different culture conditions, serum survival assays, and virulence in a sepsis mouse model. Their genotypic characterizations included polymerase chain reaction phylotyping, whole genome sequencing, and a subsequent in silico analysis. We highlighted a selection process of highly extraintestinal virulent strains, mainly belonging to the B2 phylogroup, adapted to the hostile environment (high citrate concentration and a bactericidal serum effect) of apheresis-collected platelet concentrates (PCs). Compared to controls, the E. coli TTBI strains grew faster in the PCs due to a superior ability to capture iron. The in vitro growth performances were highly compatible with blood-derived product real-life conditions, including storage conditions and delays. The consistent serum resistance of TTBI strains promotes their survival in both the donor's and the receiver's blood and in the PCs. This study pointed out that E. coli strains responsible for TTBI exhibit very specific traits. They belong to the extraintestinal pathogenic phylogroups and have a high intrinsic virulence. They can be resistant to complement, capture iron, and grow in the apheresis-collected PCs. These findings therefore support the reinforcement of the postdonation information.

Pathogen inactivation/reduction technologies for platelet transfusion: Where do we stand?

Pathogen inactivation or reduction technologies for platelet components have been proposed to secure the microbial safety of this component, and particularly the microbial contamination. Transfusion-transmitted bacterial infections were substantially reduced by additive steps applied at different levels of the transfusion chain, but still killed one recipient each year or every other year in a country like France. Besides, pathogen inactivation and reduction stand for eliminating most viral and protozoa infections persisting in the separated blood component. In addition, because those processes attack nucleic acids, they also aim at substantially alleviating the risk of Transfusion Associates Graft versus Host Disease, as they attack lymphocytes still comprises within the component. Meanwhile, pathogen inactivation or reduction may inflict some damages to the platelet components, that are shown to be additive to the “natural” storage lesions linked to ageing. While it is in general assumed that such processes do not expose transfused patients to an over-risk of bleeding, and are safe, this does not mean that there are no detrimental consequences in the patients, even if not ascribed to as serious. Two such effects are now discussed or debated: the first one is the possible increase in the demand of platelet component, and the other one could be a possible risk of alloimmunisation especially when treated platelets are aged (over 5 days). Three processes have been made available by the industry, that differ in their chemical and physical (ultraviolet light illumination) characteristics. Two processes are largely used (one nationwide in two European countries) and the third one is still under clinical evaluation. This short review endeavored to critically present the main features of the processes and of their implementation.

Nationwide Implementation of Pathogen Inactivation for All Platelet Concentrates in Switzerland

Introduction: Bacterial contamination of platelet concentrates (PCs) has been identified as the most prevalent transfusion-associated infectious risk. To prevent PC-related septic transfusion reactions, the Intercept® pathogen inactivation procedure was introduced for all PCs in Switzerland in 2011. Methods: Based on numbers of transfused units and mandatorily reported adverse events with high imputability, we compare the risks associated with transfusion of conventional PCs (cPCs) and pathogen-inactivated PCs (PI-PCs). Results: From 2005 to 2011, a total of 158,502 cPCs have been issued in Switzerland, and 16 transfusion-transmitted bacterial infections (including 3 fatalities) were reported. This corresponds to a morbidity and mortality rate of ca. 1:9,900 and 1:52,800, respectively. From 2011 to 2016, a total of 205,574 PI-PCs have been issued, and no transfusion-transmitted bacterial infection was reported. Despite continuously increasing transfusion reaction rates per 1,000 RBC and plasma issued between 2008 and 2016, we observed reductions of 66% for life-threatening and fatal reactions and of 26% for all high-imputability transfusion reactions related to PI-PCs as compared to cPCs. No increased rates of bleeding or clinical observations of ineffectiveness of PI-PCs have been reported. After implementation of PI-PCs, the annual increase in platelet usage per 1,000 inhabitants decelerated. Discussion: Swiss hemovigilance data confirm a favorable safety profile of the nationwide introduced Intercept pathogen inactivation procedure and its reliable prevention of septic transfusion reactions and fatalities due to bacterially contaminated PCs.

Storage time of platelet concentrates and risk of a positive blood culture: a nationwide cohort study.

Concern of transfusion-transmitted bacterial infections has been the major hurdle to extend shelf life of platelet (PLT) concentrates. We aimed to investigate the association between storage time and risk of positive blood cultures at different times after transfusion. We performed a nationwide cohort study among PLT transfusion recipients in Denmark between 2010 and 2012, as recorded in the Scandinavian Donations and Transfusions (SCANDAT2) database. Linking with a nationwide database on blood cultures (MiBa), we compared the incidence of a positive blood culture among recipients of PLTs stored 6 to 7days (old) to those receiving fresh PLTs (1-5 days), using Poisson regression models. We considered cumulative exposures in windows of 1, 3, 5, and 7 days. A total of 9776 patients received 66,101 PLT transfusions. The incidence rate ratio (IRR) of a positive blood culture the day after transfusion of at least one old PLT concentrate was 0.77 (95% confidence interval [CI], 0.54-1.09) compared to transfusion of fresh PLT concentrates. The incidence rate of a positive blood culture was lower the day after receiving one old compared to one fresh PLT concentrate (IRR, 0.57; 95% CI, 0.37-0.87). Three, 5, or 7 days after transfusion, storage time was not associated with the risk of a positive blood culture. Storage of buffy coat-derived PLT concentrates in PAS-C up to 7days seems safe regarding the risk of a positive blood culture. If anything, transfusion of a single old PLT concentrate may decrease this risk the following day.