A Cardiovascular Disease-Linked Gut Microbial Metabolite Acts via Adrenergic Receptors.

Using untargeted metabolomics (n = 1,162 subjects), the plasma metabolite (m/z = 265.1188) phenylacetylglutamine (PAGln) was discovered and then shown in an independent cohort (n = 4,000 subjects) to be associated with cardiovascular disease (CVD) and incident major adverse cardiovascular events (myocardial infarction, stroke, or death). A gut microbiota-derived metabolite, PAGln, was shown to enhance platelet activation-related phenotypes and thrombosis potential in whole blood, isolated platelets, and animal models of arterial injury. Functional and genetic engineering studies with human commensals, coupled with microbial colonization of germ-free mice, showed the microbial porA gene facilitates dietary phenylalanine conversion into phenylacetic acid, with subsequent host generation of PAGln and phenylacetylglycine (PAGly) fostering platelet responsiveness and thrombosis potential. Both gain- and loss-of-function studies employing genetic and pharmacological tools reveal PAGln mediates cellular events through G-protein coupled receptors, including α2A, α2B, and ß2-adrenergic receptors. PAGln thus represents a new CVD-promoting gut microbiota-dependent metabolite that signals via adrenergic receptors.

Nucleation of platelets with blood-borne pathogens on Kupffer cells precedes other innate immunity and contributes to bacterial clearance.

Through the use of intravital imaging of the liver, we demonstrate a collaborative role for platelets with Kupffer cells (KCs) in eradicating blood-borne bacterial infection. Under basal conditions, platelets, via the platelet-adhesion receptor GPIb, formed transient 'touch-and-go' interactions with von Willebrand factor (vWF) constitutively expressed on KCs. Bacteria such as Bacillus cereus and methicillin-resistant Staphylococcus aureus (MRSA) were rapidly caught by KCs and triggered platelets to switch from 'touch-and-go' adhesion to sustained GPIIb-mediated adhesion on the KC surface to encase the bacterium. Infected GPIbα-deficient mice had more endothelial and KC damage than did their wild-type counterparts, which led to more fluid leakage, substantial polycythemia and rapid mortality. Our study identifies a previously unknown surveillance mechanism by which platelets survey macrophages that rapidly converts to a critical host response to blood-borne bacteria.

Comparable bacterial growth in platelet concentrates suspended in plasma and platelet additive solution and improved detection of bacterial contamination using a new generation automated culture system.

BACKGROUND: Microbial screening of platelet concentrates (PC) with automated culture methods is widely implemented to reduce septic transfusion reactions. Herein, detection of bacterial contamination in PC was compared between units prepared in plasma and a mix of plasma and platelet additive solution (PAS) and between the BACT/ALERT 3D and next generation BACT/ALERT VIRTUO systems. STUDY DESIGN/METHODS: Double apheresis units were split into single units, diluted in either PAS (PAS-PC) or plasma (plasma-PC), and tested for in vitro quality and sterility prior to spiking with ~30 CFU/unit of Staphylococcus epidermidis, Staphylococcus aureus, Serratia marcescens, and Klebsiella pneumoniae or ~10 CFU/mL of Cutibacterium acnes. Spiked PC were sampled for BACT/ALERT testing (36 and 48 h post-spiking) and colony counts (24, 36, and 48 h post-spiking). Times to detection (TtoD) and bacterial loads were compared between PC products and BACT/ALERT systems (N = 3). RESULTS: Bacterial growth was similar in plasma-PC and PAS-PC. No significant differences in TtoD were observed between plasma-PC and PAS-PC at the 36-h sampling time except for S. epidermidis which grew faster in plasma-PC and C. acnes which was detected earlier in PAS-PC (p < .05). Detection of facultative bacteria was 1.3-2.2 h sooner in VIRTUO compared with 3D (p < .05) while TtoD for C. acnes was not significantly different between the two systems. DISCUSSION: Comparable bacterial detection was observed in plasma-PC and PAS-PC with PC sampling performed at 36-h post blood collection. PC sampling at ≤36 h could result in faster detection of facultative pathogenic organisms with the VIRTUO system and improved PC safety.

The operational and financial impact of adding anaerobic screening of platelets.

BACKGROUND AND OBJECTIVES: We evaluated the operational and safety impact of implementing anaerobic culture screening of apheresis and pooled platelets at the American Red Cross on the already established use of the aerobic culture screening of each donation performed no sooner than 24 h following collection. MATERIALS AND METHODS: Platelets were screened for bacterial contamination with the BACT/ALERT 3D® (bioMérieux, Durham, NC) microbial detection testing system. The addition of anaerobic culture to the already existing aerobic culture resulted in sampling an additional 8-10 mL from each donation. RESULTS: Implementation of anaerobic testing resulted in an approximate 3.5-fold increased rate of False Positive BACT/ALERT alarms. There was a modest increase in the rate of True Positive alarms of 1.4-fold with increased detection of Klebsiella and Propionibacterium species, including Cutibacterium acnes. In addition, there was an approximate 3.5-fold increase rate of False Positives and a 13.5-fold increase rate of Indeterminates, the majority (~57%) were due to Cutibacterium acnes. The combined costs and lost revenue associated with adding anaerobic screening increased by ~$1,000,000/year due to testing cost and product discards. CONCLUSION: The addition of anaerobic culture to aerobic culture to the original donation (without the introduction of sampling delay) resulted in a significant increase in the rate of alerts. The 40% increased rate of True Positive alarms may have modestly improved platelet safety. However, there was a disproportionate increase in the rate of False Positive and Indeterminate bacterial culture alarms, which added substantial cost and overall loss of platelet products.

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.

Use of flow cytometry method to detect contaminations of platelet suspensions.

In this study, it was aimed to investigate bacterial contamination in apheresis platelet suspensions (APS) by automated blood culture system and flow cytometry method (FCM).33 spiked APS each using 11 bacterial strains (5 standard strains, 6 clinical isolates), were prepared in three different dilutions (1-10, 10-50, 50-100 cfu/mL), incubated in two different temperatures (35-37 °C and 22-24 °C) and different incubation times (18-96 h) evaluated by FCM. This three different dilutions were also inoculated into special platelet culture bottles (BacT/ALERT® BPA) and loaded into the blood culture system. Additionally 80 APSs routinely prepared in the Transfusion Center were evaluated by both FCM and the blood culture system. Platelets were lysed by freeze-thaw method.All spiked samples were positive with BacT/ALERT® BPA in 12-18 h. In 96 h incubation at 22-24 °C, the presence of bacteria was detected by FCM in all other samples (31/33) except low dilutions (1-10 and 10-100 CFU/ml) of K.pneumoniae standard strain. In the 35-37 °C, the presence of bacteria was detected by FCM in all samples (33/33) after 48 h of incubation. In routine APS one sample detected as positive (Bacillus simplex) with BacT/ALERT® BPA and no positivity was detected by FCM.The freeze-thaw method, which we have optimized for the lysis of platelets, is very practical and can be easily applied. The BacT/ALERT® system has been found to be very sensitive in detecting bacterial contamination in PSs. Flow cytometry method has been found to be successful, fast, easy to use and low cost in detecting bacterial contamination in PSs.

A platelet-mediated system for shuttling blood-borne bacteria to CD8α+ dendritic cells depends on glycoprotein GPIb and complement C3.

The acquisition of pathogen-derived antigen by dendritic cells (DCs) is a key event in the generation of cytotoxic CD8(+) T cell responses. In mice, the intracellular bacterium Listeria monocytogenes is directed from the blood to splenic CD8α(+) DCs. We report that L. monocytogenes rapidly associated with platelets in the bloodstream in a manner dependent on GPIb and complement C3. Platelet association targeted a small but immunologically important portion of L. monocytogenes to splenic CD8α(+) DCs, diverting bacteria from swift clearance by other, less immunogenic phagocytes. Thus, an effective balance is established between maintaining sterility of the circulation and induction of antibacterial immunity by DCs. Other gram-positive bacteria also were rapidly tagged by platelets, revealing a broadly active shuttling mechanism for systemic bacteria.

Increased frequency of false-positive bacterial detection after implementation of new guidelines for large-volume delayed sampling of platelets.

BACKGROUND: The updated guidance for improving bacterial detection (BD) of platelets has included the implementation of large-volume delayed sampling (LVDS) with the addition of anaerobic culture bottles (BPNs) and sampling of each platelet split product. METHODS: The frequency of BD was reviewed during this LVDS time period in comparison with pre-LVDS and the Post-Approval Surveillance Study of Platelet Outcomes, Release Tested (PASSPORT) study (when BPNs were last used). RESULTS: There was more than a twofold increase in bottles inoculated per collection during LVDS, with an almost fivefold increase in sample volume collected. During LVDS, the concordance of split products within an initial reactive collection was only 8.7%. There was no difference in LVDS aerobic culture bottle (BPA) true positives (TPs), but there was a significant increase in LVDS false positives (FPs), p < .0001, compared to both PASSPORT and pre-LVDS, respectively. There was an increase in BPN TPs during LVDS (p < .05 compared to PASSPORT), with predominance of Cutibacter acnes (C. acnes), noted exclusively in BPN, and accounting for more than two-fifths of all organisms detected. Time to alarm during LVDS for TPs had two peaks with one due to C. acnes at 96 h compared to 17 h for non-C. acnes. DISCUSSION: The high FP frequency, along with low clinical significance of TPs found in BPNs, has led to the needless discard of inventory, as the utility of BPNs in BD for platelets is yet to be established and may require much larger studies.

Bacterial culture time to detection in platelet components: An evidence synthesis and estimation of detection failures.

BACKGROUND: Non-pathogen reduction platelet bacterial risk control strategies in the US FDA guidance include at least one culture. Almost all of these strategies have a culture hold time of ≥12 h. Studies have reported time to detection (TTD) of bacterial cultures inoculated with bacteria from contaminated platelets, but these data and estimates of risk associated with detection failures have not been synthesized. METHODS: We performed a literature search to identify studies reporting TTD for samples obtained from spiked platelet components. Using extracted data, regression analysis was used to estimate TTD for culture bottles at different inoculum sizes. Detection failures were defined as events in which contaminated components are transfused to a patient. We then used published data on time of transfusion (ToT) to estimate the risk of detection failures in practice. RESULTS: The search identified 1427 studies, of which 16 were included for analysis. TTD data were available for 16 different organisms, including 14 in aerobic cultures and 11 in anaerobic cultures. For inocula of 1 colony forming unit (CFU), the average TTD for aerobic organisms was 19.2 h while it was 24.9 h in anaerobic organisms, but there was substantial overall variation. A hold time of 12 versus 24 h had minimal effect for most organisms. CONCLUSION: TTD variation occurs between bacterial species and within a particular species. Under typical inventory management, the relative contribution of culture detection failures is much smaller than the residual risk from sampling failures. Increasing the hold period beyond 12 h has limited value.

Whole blood derived and apheresis platelets: Opinions and preferences-the results of a national survey of blood collectors.

INTRODUCTION: Currently greater than 94% of the US platelet supply is collected by apheresis. A survey to determine the attitudes of members of America's Blood Centers (ABC) toward whole blood derived (WBD) platelets was designed in light of current platelet supply issues. METHODS: An on-line survey was distributed to medical directors of the 47 ABC members. RESULTS: Responses were received from 44/47 (94%) ABC members. There were 15/43 (35%) centers that are currently providing WBD platelets. Seventy percent of the respondents agreed or agreed strongly that WBD and apheresis platelets were clinically equivalent, with approximately 16% indicating that they did not have an opinion on their equivalency and 14% indicating that they were not clinically equivalent. Forty-four percent of respondents felt that their customers would agree or strongly agree that these products are clinically equivalent, while 26% felt that their customers did not know or were neutral on clinical equivalency. The main barrier to WBD platelet implementation was logistic/inventory management issues, followed by bacterial contamination risk mitigation. There were 21/43 (49%) respondents who indicated they are not considering producing WBD platelets to mitigate shortages. Respondents indicated they might begin producing WBD platelets if there was evidence of increasing customer demand, increased reimbursement, inability to supply apheresis platelets, if pathogen reduction became available for WBD platelets, if the platelet shortage worsened. CONCLUSIONS: The majority of blood collectors consider WBD platelets clinically equivalent to apheresis, however wider adoption of WBD platelets is still hindered by challenges with logistics and inventory management.

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.

BACKGROUND: 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 2018 and 2019. 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. METHODS: 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). RESULTS: 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. DISCUSSION: Longitudinal HV analysis demonstrated stable PC utilization trends with reduced patient risk during conversion to universal 7-day amotosalen/UVA PCs.

Nutrient supplementation of culture media improves the detection of Cutibacterium acnes in platelet components by an automated culture system.

BACKGROUND AND OBJECTIVES: Platelet concentrates (PCs) contaminated with Cutibacterium acnes are often transfused prior to detection by the BACT/ALERT system. Though C. acnes is implicated in mild transfusion reactions, delayed clinical effects are unknown. This study assessed the ability to enhance C. acnes detection by supplementing culture media with Tween 80 (T80, an oleic acid source) and a commercial nutrient supplement. MATERIALS AND METHODS: Anaerobic culture bottles (BPN) were supplemented with T80 or oleic acid. T80-supplemented BPN bottles were inoculated with four C. acnes isolates (10 or 100 colony-forming units [CFU]/bottle) or other transfusion-relevant bacteria (10 CFU/bottle). Samples of plasma containing SSP+ (platelet additive solution [PAS]) (PAS-plasma) at different concentrations, plasma-PCs and PAS-PCs, spiked with two C. acnes isolates (10 CFU/bottle), were inoculated into T80-supplemented BPN bottles. Furthermore, plasma-PCs were spiked with C. acnes and tested in BPN bottles supplemented with the BD Difco Supplement VX (BDVx). Bottles were incubated in the BACT/ALERT system and times to detection (TtoD) were compared (N = 3). RESULTS: A reduction in TtoD of ≤3.5 days was observed for C. acnes in T80-supplemented BPN, while other species did not show the same effect. However, false positives were observed when T80-supplemented BPN was inoculated with PAS-plasma (except for 70% PAS:30% plasma), plasma-PCs or PAS-PCs. Oleic acid supplementation also resulted in false positives. Interestingly, BDVx-supplemented BPN reduced the TtoD of C. acnes in PCs by ≤1.2 days (p < 0.05), with no false-positive results. CONCLUSION: BDVx supplementation for detection of C. acnes from PCs could result in timely unit retrieval, preventing the transfusion of contaminated products. In clinical settings, T80 supplementation could significantly enhance C. acnes detection from non-blood-derived samples.

Time from apheresis platelet donation to cold storage: Evaluation of platelet quality and bacterial growth.

BACKGROUND: Cold storage reduces posttransfusion survival of platelets; however, it can improve platelet activation, lower risk of bacterial contamination, and extend shelf-life compared to room temperature (RT) storage. To facilitate large-scale availability, manufacturing process optimization is needed, including understanding the impact of variables on platelet potency and safety. Short time requirements from collection to storage is challenging for large blood centers to complete resuspension and qualify platelets for production. This study evaluated the impact of time from platelet component collection to cold storage on in vitro properties and bacterial growth. STUDY DESIGN AND METHODS: Double-apheresis platelet components were collected from healthy donors, suspended in 65% PAS-III/35% plasma, and split into 2 equal units. One unit was placed into cold storage within 2 h and the other unit after 8 h. Eight matched pairs were evaluated for 12 in vitro parameters. Twenty-four matched pairs were evaluated with 8 bacterial strains tested in triplicate. Samples were tested throughout 21 days of storage. RESULTS: In vitro properties were not different between 2 and 8 h units, and trends throughout storage were similar between arms. Time to cold storage did not significantly impact bacterial growth, with <1 log10 difference at all timepoints between units. DISCUSSION: Our studies showed that extending time to cold storage from 2 to 8 h from collection did not significantly increase the bacterial growth, and the platelet component quality and function is maintained. The ability to extend the time required from collection to storage will improve blood center logistics to feasibly produce CSPs.

Implementation strategy for complete pathogen reduction technology treated apheresis platelet inventory.

BACKGROUND: Bacterial contamination in platelets remain a major public health concern, which prompted the US Food and Drug Administration guidance for bacterial contamination mitigation. Pathogen reduction technology (PRT) is one mitigation strategy that has shown success in Europe over the last decade. Therefore, our center sought to transition from a dual system of bacterial culturing (BacT) and PRT to full PRT. METHODS: A 1 month pilot study was conducted to simulate 100% PRT conditions. Our center also collected baseline data on key platelet production metrics in the 4 months prior to 100% PRT and compared it to the 4 months post-implementation. RESULTS: The pilot study showed no statistical differences in split rate, proportion of low-yield products, or proportion of single, double, and triple collections. The only observed difference was an 11 min increase in the average duration of double collections. Our baseline versus post-implementation monitoring showed no difference in split rate, discard rate, percentage of low-yield units, and average yield of low yield units. Statistical differences were detected in the proportion of single, double, and triple collections, as well as the average yield of full dose products. Roughly 20% of our inventory consisted of low-yield products. DISCUSSION: With suitable mitigation strategies, transitioning to a full PRT inventory may result in higher net margins while not adversely affecting overall platelet production. A pilot study is a good way to project potential effects of switching from a dual BacT and PRT inventory to full PRT, and can be adopted by other centers aiming to make the transition.

Economic implications of FDA platelet bacterial guidance compliance options: Comparison of single-step strategies.

BACKGROUND: Bloodborne pathogens pose a major safety risk in transfusion medicine. To mitigate the risk of bacterial contamination in platelet units, FDA issues updated guidance materials on various bacterial risk control strategies (BRCS). This analysis presents results of a budget impact model updated to include 5- and 7-day pathogen reduced (PR) and large volumed delayed sampling (LVDS) BRCS. STUDY DESIGN AND METHODS: Model base-case parameter inputs were based on scientific literature, a survey distributed to 27 US hospitals, and transfusion experts' opinion. The outputs include hospital budget and shelf-life impacts for 5- and 7-day LVDS, and 5- and 7-day PR units under three different scenarios: (1) 100% LVDS, (2) 100% PR, and (3) mix of 50% LVDS - and 50% PR. RESULTS: Total annual costs from the hospital perspective were highest for 100% LVDS platelets (US$2.325M) and lowest for 100% PR-7 units (US$2.170M). Net budget impact after offsetting annual costs by outpatient reimbursements was 5.5% lower for 5-day PR platelets as compared to 5-day LVDS (US$1.663 vs. US$1.760M). A mix of 7-day LVDS and 5-day PR platelets had net annual costs that were 1.3% lower than for 100% 7-day LVDS, but 1.3% higher than for 100% 5-day PR. 7-day PR platelets had the longest shelf life (4.63 days), while 5-day LVDS had the shortest (2.00 days). DISCUSSION: The model identifies opportunities to minimize transfusion center costs for 5- and 7-day platelets. Budget impact models such as this are important for understanding the financial implications of evolving FDA guidance and new platelet technologies.

Association of Staphylococcus aureus in platelet concentrates with skin diseases in blood donors: Limitations of cultural bacterial screening.

BACKGROUND: Bacterial contamination in platelet concentrates (PCs) is a major problem in transfusion medicine. Contamination with Staphylococcus aureus is occasionally missed, even with cultural screening. STUDY DESIGN AND METHODS: Donors implicated in S. aureus-contaminated PC were followed up. Skin and nasal swab specimens from six donors and S. aureus isolated from PCs related to these donors were subjected to multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) to determine the identity of bacteria. To evaluate the validity of the screening method using BacT/ALERT 3D, we spiked S. aureus and three other bacterial species as comparisons into PCs and investigated their growth pattern. RESULTS: S. aureus was isolated from all nasal specimens and from the arm skin specimens of three donors with atopic dermatitis. In all cases, the S. aureus strains isolated from the PC and those from the nasal and skin specimens of the same donor showed concordant results using MLST and PFGE. In the spiking study, S. aureus showed irregular detectability over 24 to 48 h post-spike periods, whereas the three other bacterial species were detected in all culture bottles after a 24-h post-spike period. DISCUSSION: The strain identity of S. aureus between donor and PC suggests that the contaminants were derived from those colonized in the donor. Furthermore, S. aureus yielded false-negative results using BacT/ALERT 3D.

Transfusion outcomes between regular and low yield pathogen reduced platelets across different patient populations in a single institution.

BACKGROUND: Pathogen reduction technology (PRT) effectively mitigates bacterial contamination in platelets but is more likely to produce low yield units. Although low dose transfusion using conventional platelets has not been associated with increased bleeding, these findings have not been reproduced with PRT-treated platelets. STUDY DESIGN AND METHODS: Platelet transfusions in a tertiary adult hospital were retrospectively reviewed. Comparisons were made between PRT-treated regular (PRT-PR) and low (PRT-PL) yield platelets. Outcomes examined included the number of platelets and RBCs transfused, transfusion-free interval, and corrected count increment (CCI). Subgroup analyses were also performed on hematology-oncology inpatients and outpatients, as well as non-hematology-oncology patients. RESULTS: Platelet utilization per patient remained mostly unchanged (mean 2.9-4.3 units per patient per month) even when the frequency of PRT-PL transfusion increased. Among 1402 patients examined, the number of platelets and RBCs transfused was not significantly different between patients first transfused with PRT-PR versus PRT-PL (mean number of platelet units = 2.8 vs. 3.1, p = 0.38; mean number of RBC units = 4.8 vs. 4.3, p = 0.93). Among 10,257 platelet transfusions examined, the transfusion-free interval (hazard ratio = 1.05, 95% confidence interval 1.00-1.10) and CCI (10.2 vs. 11.0, p = 0.70) were comparable between PRT-PR and PRT-PL units. Similar findings were observed in all subgroups, except for shortened transfusion-free intervals among hematology-oncology inpatients. CONCLUSION: PRT-PR and PRT-PL units may be used in an equivalent manner to maintain an adequate platelet inventory, since there was only a minor difference in time between transfusions.

Acquired platelet storage container leaks and contamination with environmental bacteria: A preventable cause of bacterial sepsis.

BACKGROUND: Apheresis platelets (AP) may be contaminated by environmental bacteria via container defects acquired during processing, transport, storage, or transfusion, as highlighted by a recent series of septic reactions related to Acinetobacter spp. and other bacterial strains. STUDY DESIGN AND METHODS: The frequency and nature of acquired container defect reports to one manufacturer were evaluated from January 2019 to July 2020. The published incidence of contamination and sepsis due to environmental bacteria with culture screened AP in the United States was reviewed for the period of 2010-2019. RESULTS: Review of a manufacturers' records showed 23 US reports of leaks involving 24 containers attributed to postmanufacturing damage, at a rate of 44 per million distributed storage containers. Analysis of returned containers showed evidence of scratches, impressions, and/or piercings. Literature review of US hemovigilance data revealed that environmental bacteria comprised 7% of confirmed positive primary bacterial culture screens, were responsible for 14%-16% of reported septic, and 8 of 28 (29%) fatal reactions with bacterial-culture screened AP. Sepsis cases have been reported with culture screened, point-of-issue (POI) tested, or pathogen-reduced AP. DISCUSSION: Environmental contamination of AP is rare but can cause sepsis. Container damage provides a pathway for contamination after culture screening, POI bacteria testing, or pathogen reduction. Blood collectors and transfusion services should have procedures to ensure proper inspection, handling, storage, and transport of AP to avoid damage and should enhance efforts to detect defects prior to release and to eliminate bacteria from all contacting surfaces to minimize the risk of contamination.

Contamination of platelet concentrates with Staphylococcus aureus induces significant modulations in platelet functionality.

BACKGROUND AND OBJECTIVES: Platelet concentrates (PCs) contaminated with Staphylococcus aureus can escape detection during PC screening, causing septic transfusion reactions. This study aimed to determine the impact of S. aureus contamination on platelet metabolism and functionality during PC storage. MATERIALS AND METHODS: Targeted metabolomics (N = 3) was performed on non-spiked PCs and PCs inoculated with 10-20 colony-forming units (CFU)/bag of S. aureus. Metabolites were quantified at 0, 48 and 144 h using high-performance mass spectrometry (MS). Additionally, PCs spiked with approximately 20 CFU/bag of S. aureus were sampled every 24 h for up to 144 h to evaluate platelet functionality using flow cytometry (N = 2). RESULTS: Eight metabolites had significantly different levels in spiked PCs (log2 fold-change ≤ or ≥±1) versus non-spiked units at 48 and 144 h. Xanthine, uridine, serine, glutamine and threonine were increased, whereas orotic acid, dihydroorotic acid and aspartic acid were decreased. Flow cytometry showed a significant decrease in expression of GPIIb while P-selectin expression was significantly increased in spiked PCs after 72 h of storage when S. aureus concentration was ≥10E+08 CFU/ml. Additionally, phosphatidylserine exposure was significantly increased after 48 h of PC storage, when S. aureus had reached a concentration of 2E+06. CONCLUSION: Contamination with S. aureus exacerbates platelet storage lesions in contaminated PCs but only when the bacterium has reached clinically significant levels.

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.