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Safety of Platelet Components: Past, Present and Future

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A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 7888

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Special Issue Editors

Dr. Sandra Ramirez-Arcos

E-Mail Website
Guest Editor

Canadian Blood Services, Ottawa, ON, Canada
Interests: platelet components; bacterial contamination in platelets

Dr. Carl McDonald

E-Mail Website
Co-Guest Editor

Retired. Former Head of the National Bacteriology Laboratory and Scientific Consultant for NHSBT, London, UK
Interests: platelet components

Special Issue Information

Dear Colleagues,

Blood components are life-saving products produced under good manufacturing practices. Three blood components can be produced from one whole blood collection: plasma, red blood cell concentrates and platelet components (PCs). Within this trio, PCs pose the highest safety risk to transfusion patients, as they must be stored at 20-24 °C in glucose-rich solutions with neutral pH, under agitation, for up to 7 days.These conditions are needed to maintain platelet functionality, but they also provide an ideal environment for the proliferation of any bacteria introduced during blood collection.The predominant PC bacterial contaminants are part of the normal skin flora, although organisms implicated in silent blood donor bacteremia could also be present in the collected blood. Strategies implemented to minimize the risk of transfusing bacterially-contaminated PC include testing with culture-based methods or rapid assays or treatment with pathogen reduction (PR) technologies. While these mitigation approaches have greatly enhanced PC safety, a residual risk still remains, as exemplified by recent reports of septic transfusion cases. This Special Issue will allow the transfusion medicine community to look back at the progress made to enhance PC safety in recent decades, reflect on the present status of bacterial contamination in PCs, and discuss potential residual risks and challenges to prevent future septic transfusion reactions.

This Special Issue aims at providing an overview of the past, current and future status of bacterial contamination in PCs with a focus on providing new insights for transfusion patient safety.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but not limited to) the following:

The history of bacterial contamination in PCs and progress to reduce risk for transfusion patients in the last few decades;
The status of bacterial contamination in PCs worldwide: how low-income countries compare to high-income countries;
Surveillance data of bacterial contamination in PCs;
Incidence of septic transfusion reactions;
Research studies on bacterial growth in PCs;
Research studies on bacterial biofilm formation in PCs;
Research studies on bacterial toxin production in PCs;
Strategies to improve PC safety: focus on testing methods;
Strategies to improve PC safety: focus on pathogen reduction methods;PC quality and metabolomics changes resulting from bacterial contamination;
Climate change and emergent bacterial pathogens that could affect PC safety.

I look forward to receiving your contributions.

Dr. Sandra Ramirez-Arcos
Dr. Carl McDonald
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

platelet components
bacterial contamination in platelets

Published Papers (7 papers)

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Research

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10 pages, 1764 KiB

Open AccessArticle

The Preclinical Validation of 405 nm Light Parasiticidal Efficacy on Leishmania donovani in Ex Vivo Platelets in a Rag2^−/− Mouse Model

by Pravin R. Kaldhone, Nazli Azodi, Hannah L. Markle, Neetu Dahiya, Caitlin Stewart, John Anderson, Scott MacGregor, Michelle Maclean, Hira L. Nakhasi, Sreenivas Gannavaram and Chintamani Atreya

Microorganisms 2024, 12(2), 280; https://doi.org/10.3390/microorganisms12020280 - 29 Jan 2024

Viewed by 753

Abstract

Violet–blue light of 405 nm in the visible spectrum at a dose of 270 J/cm² alone has been shown to be an effective microbicidal tool for inactivating several bacteria, HIV-1, and Trypanosoma cruzi in ex vivo plasma and platelets. Unlike chemical- and ultraviolet (UV)-based pathogen inactivation methods for plasma and platelet safety, 405 nm light is shown to be less toxic to host cells at light doses that are microbicidal. In this report, we evaluated the parasiticidal activity of a 405 nm light treatment on platelets spiked with the Leishmania donovani parasite. Following the light treatment, parasite viability was observed to be near zero in both low- and high-titer-spiked platelets relative to controls. Furthermore, to test the residual infectivity after inactivation in vivo, the light-treated low-titer L. donovani-spiked platelets were evaluated in an immunodeficient Rag2^−/− mouse model and monitored for 9 weeks. The parasiticidal efficacy of 405 nm light was evident from the lack of a presence of parasites in the mice spleens. Parasiticidal activity was confirmed to be mediated through 405 nm light-induced reactive oxygen species (ROS), as quantitatively measured by a 2′,7′-Dichlorodihydrofluorescein diacetate (H₂DCFDA)-based assay. Overall, these results confirm the complete inactivation of L. donovani spiked in ex vivo platelets by 405 nm light treatment and exemplify the utility of the Rag2^−/− mouse infection model for the preclinical validation of the parasiticidal efficacy of 405 nm light and this light-based technology as a potential PRT for ex vivo platelets. Full article

(This article belongs to the Special Issue Safety of Platelet Components: Past, Present and Future)

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15 pages, 3117 KiB

Open AccessArticle

Sebum Components Dampen the Efficacy of Skin Disinfectants against Cutibacterium acnes Biofilms

by Dilini Kumaran and Sandra Ramirez-Arcos

Microorganisms 2024, 12(2), 271; https://doi.org/10.3390/microorganisms12020271 - 27 Jan 2024

Viewed by 1019

Abstract

At Canadian Blood Services, despite the use of 2% chlorhexidine and 70% isopropyl alcohol (standard disinfectant, SD) prior to venipuncture, Cutibacterium acnes evades eradication and is a major contaminant of platelet concentrates (PCs). Since C. acnes forms bacterial aggregates known as biofilms in the sebaceous niches of the skin, this study aimed to assess whether sebum-like components impact disinfectant efficacy against C. acnes leading to its dominance as a PC contaminant. C. acnes mono-species and dual-species biofilms (C. acness and a transfusion-relevant Staphylococcus aureus isolate) were formed in the presence and absence of sebum-like components and exposed to SD, a hypochlorous acid-based disinfectant (Clinisept+, CP), or a combination of both disinfectants to assess disinfectant efficacy. Our data indicate that sebum-like components significantly reduce the disinfectant efficacy of all disinfectant strategies tested against C. acnes in both biofilm models. Furthermore, though none of the disinfectants led to bacterial eradication, the susceptibility of C. acnes to disinfectants was heightened in an isolate-dependent manner when grown in the presence of S. aureus. The reduction of skin disinfection efficacy in the presence of sebum may contribute to the overrepresentation of C. acnes as a PC contaminant and highlights the need for improved disinfection strategies. Full article

(This article belongs to the Special Issue Safety of Platelet Components: Past, Present and Future)

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20 pages, 787 KiB

Open AccessArticle

Changing Strategies for the Detection of Bacteria in Platelet Components in Ireland: From Primary and Secondary Culture (2010–2020) to Large Volume Delayed Sampling (2020–2023)

by Niamh O’Flaherty, Louise Bryce, James Nolan and Mark Lambert

Microorganisms 2023, 11(11), 2765; https://doi.org/10.3390/microorganisms11112765 - 14 Nov 2023

Viewed by 797

Abstract

Bacterial contamination of platelet components (PC) poses the greatest microbial risk to recipients, as bacteria can multiply over the course of PC storage at room temperature. Between 2010 and 2020, the Irish Blood Transfusion Service (IBTS) screened over 170,000 buffy coat-derived pooled (BCDP) and single-donor apheresis platelets (SDAPs) with the BACT/ALERT 3D microbial detection system (Biomerieux, L’Etoile, France), using a two-step screening protocol which incorporated primary and secondary cultures. Although the protocol was successful in averting septic transfusion reactions (STRs), testing large sample volumes at later time points was reported to improve detection of bacterial contamination. A modified large-volume delayed sampling (LVDS)-type protocol was adopted in 2020, which in the case of SDAP was applied to collections rather than individual splits (2020–2023, 44,642 PC screened). Rates of bacterial contamination for BCDP were 0.125% on Day-2, 0.043% on Day-4 vs. 0.191% in the post-LVDS period. SDAP contamination rates in the pre-LVDS period were 0.065% on Day-1, 0.017% on Day-4 vs. 0.072% in the post-LVDS period. Confirmed STRs were absent, and the interdiction rate for possibly contaminated SDAP was over 70%. In the post-LVDS period, BCDPs had a higher total positivity rate than SDAPs, 0.191% (1:525) versus 0.072% (1:1385), respectively, (chi-squared 12.124, 1 df, p = 0.0005). The majority of organisms detected were skin-flora-type, low pathogenicity organisms, including coagulase-negative staphylococci and Cutibacterium acnes, with little change in the frequency of clinically significant organisms identified over time. Both protocols prevented the issue of potentially harmful components contaminated (rarely) with a range of pathogenic bacteria, including Escherichia coli, Serratia marcesens, Staphylococcus aureus, and streptococci. Culture positivity of outdates post-LVDS whereby 100% of expired platelets are retested provides a residual risk estimate of 0.06% (95% CI 0.016–0.150). However, bacterial contamination rates in expired platelets did not demonstrate a statistically significant difference between the pre-LVDS 0.100% (CI 0.033–0.234) and post-LVDS 0.059% (0.016–0.150) periods (chi-squared = 0.651, 1 df, p = 0.42). Full article

(This article belongs to the Special Issue Safety of Platelet Components: Past, Present and Future)

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12 pages, 860 KiB

Open AccessArticle

Dual-Temperature Microbiological Control of Cellular Products: A Potential Impact for Bacterial Screening of Platelet Concentrates?

by Tanja Vollmer, Cornelius Knabbe and Jens Dreier

Microorganisms 2023, 11(9), 2350; https://doi.org/10.3390/microorganisms11092350 - 20 Sep 2023

Viewed by 739

Abstract

An experimental study by the Paul-Ehrlich Institute (PEI) demonstrated that temperatures between 35 and 37 °C are too high for the growth of some bacterial strains (e.g., Pseudomonas fluorescens), leading to false negative results. Thus, the question of whether it is necessary to adapt incubation temperatures for the microbiological control of blood products, especially platelet concentrates (PCs), to enhance safety and regulatory compliance has arisen. In order to further elucidate this issue, the growth capability of different bacterial strains of interest in PCs and the detection efficacy of cultivation of these at different incubation temperatures must be taken into account. Therefore, we inoculated PCs with 46 different strains (3–6 PCs from different donors per strain) from different origins (PC isolates, reference strains) and stored PCs at 20–22 °C under constant agitation. On day three of storage, the inoculated PCs were sampled; aerobic and anaerobic culture bottles (BacT/Alert AST/NST) were each inoculated with 5 mL of sample, and culture bottles were incubated at 25 and 35 °C using the automated BacT/Alert Dual-temperature system. Bacterial proliferation was enumerated using a colony-forming assay. All strains of Enterobacteriacae (n = 5), Staphy-lococcus spp. (n = 11), Streptococcus spp. (n = 5), and Bacillus spp. (n = 4) and most Pseudomonas aeruginosa strains (4 of 5) tested showed the capability to grow in most inoculated PCs, revealing a faster time to detection (TTD) at an incubation temperature of 35 °C. The tested Pseudomonas putida (n = 3) strains showed a noticeably reduced capability to grow in PCs. Nonetheless, those with a notable growth capability revealed a faster TTD at an incubation temperature of 35 °C. Only one of the four Pseudomonas fluorescens strains tested (strain ATCC 13525) was able to grow in PCs, showing a faster TTD at an incubation temperature of 25 °C but also detection at 35 °C. The commonly detected bacteria involved in the bacterial contamination of PCs showed a superior TTD at 35 °C incubation. Only one P. fluorescens strain showed superior growth at 25 °C; however, the microbiological control at 35 °C did not fail to identify this contamination. In conclusion, the use of PC screening using a dual-temperature setting for microbiological control is presently not justified according to the observed kinetics. Full article

(This article belongs to the Special Issue Safety of Platelet Components: Past, Present and Future)

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12 pages, 1484 KiB

Open AccessArticle

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

by Anthea Cheng, Anindita Das, Khin Chaw, Peta M. Dennington, Claire E. Styles and Iain B. Gosbell

Microorganisms 2023, 11(9), 2346; https://doi.org/10.3390/microorganisms11092346 - 19 Sep 2023

Cited by 1 | Viewed by 999

Abstract

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. Full article

(This article belongs to the Special Issue Safety of Platelet Components: Past, Present and Future)

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Review

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26 pages, 1781 KiB

Open AccessReview

Bacterial Contamination of Platelet Products

by Michael R. Jacobs, Bowen Zhou, Aditi Tayal and Robert W. Maitta

Microorganisms 2024, 12(2), 258; https://doi.org/10.3390/microorganisms12020258 - 26 Jan 2024

Viewed by 1404

Abstract

Transfusion of bacterially contaminated platelets, although rare, is still a major cause of mortality and morbidity despite the introduction of many methods to limit this over the past 20 years. The methods used include improved donor skin disinfection, diversion of the first part of donations, use of apheresis platelet units rather than whole-blood derived pools, primary and secondary testing by culture or rapid test, and use of pathogen reduction. Primary culture has been in use the US since 2004, using culture 24 h after collection of volumes of 4–8 mL from apheresis collections and whole-blood derived pools inoculated into aerobic culture bottles, with limited use of secondary testing by culture or rapid test to extend shelf-life from 5 to 7 days. Primary culture was introduced in the UK in 2011 using a “large-volume, delayed sampling” (LVDS) protocol requiring culture 36–48 h after collection of volumes of 16 mL from split apheresis units and whole-blood derived pools, inoculated into aerobic and anaerobic culture bottles (8 mL each), with a shelf-life of 7 days. Pathogen reduction using amotosalen has been in use in Europe since 2002, and was approved for use in the US in 2014. In the US, recent FDA guidance, effective October 2021, recommended several strategies to limit bacterial contamination of platelet products, including pathogen reduction, variants of the UK LVDS method and several two-step strategies, with shelf-life ranging from 3 to 7 days. The issues associated with bacterial contamination and these strategies are discussed in this review. Full article

(This article belongs to the Special Issue Safety of Platelet Components: Past, Present and Future)

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16 pages, 1331 KiB

Open AccessReview

Septic Transfusion Reactions Involving Burkholderia cepacia Complex: A Review

by Margarita Salamanca-Pachon, Nohora Isabel Guayacan-Fuquene and Michel-Andres Garcia-Otalora

Microorganisms 2024, 12(1), 40; https://doi.org/10.3390/microorganisms12010040 - 25 Dec 2023

Viewed by 817

Abstract

This review was conducted to assess the global incidence of transfusion-transmitted infections (TTIs) caused by contamination of blood components with the Burkholderia cepacia complex (Bcc). Our search encompassed various specialized databases such as Medline/PubMed, Web of Science, Scopus, Scielo, ScienceDirect, and ClinicalKey. An analysis of the literature revealed a total of eleven reported cases where blood components contaminated with Bcc had been transfused, resulting in sepsis among the affected patients. Of these cases, eight were documented in the literature, while the remaining three occurred within the institution involving the authors of this review. A comparative examination was conducted, considering factors such as primary diagnosis, transfused blood component, time elapsed between transfusion and manifestation of symptoms, administration of antibiotics, and final outcome. Interestingly, regardless of the storage temperature, all blood components were found to be susceptible to Bcc contamination. Furthermore, the cases investigated revealed diverse sources of contamination, and it was observed that all the affected patients had compromised immune systems due to underlying illnesses. Based on these findings, a series of preventive strategies were derived to mitigate and decrease the occurrence of similar cases. Full article

(This article belongs to the Special Issue Safety of Platelet Components: Past, Present and Future)

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