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1.
Cost Effectiveness of Different Platelet Preparation, Storage, Selection and Dosing Methods in Platelet Transfusion: A Systematic Review
Laermans, J., Van Remoortel, H., Scheers, H., Avau, B., Georgsen, J., Nahirniak, S., Shehata, N., Stanworth, S. J., De Buck, E., Compernolle, V., et al
PharmacoEconomics - open. 2023
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Editor's Choice
Abstract
BACKGROUND AND OBJECTIVE Evidence-based guidelines on platelet transfusion therapy assist clinicians to optimize patient care, but currently do not take into account costs associated with different methods used during the preparation, storage, selection and dosing of platelets for transfusion. This systematic review aimed to summarize the available literature regarding the cost effectiveness (CE) of these methods. METHODS Eight databases and registries, as well as 58 grey literature sources, were searched up to 29 October 2021 for full economic evaluations comparing the CE of methods for preparation, storage, selection and dosing of allogeneic platelets intended for transfusion in adults. Incremental CE ratios, expressed as standardized cost (in 2022 EUR) per quality-adjusted life-year (QALY) or per health outcome, were synthesized narratively. Studies were critically appraised using the Philips checklist. RESULTS Fifteen full economic evaluations were identified. Eight investigated the costs and health consequences (transfusion-related events, bacterial and viral infections or illnesses) of pathogen reduction. The estimated incremental cost per QALY varied widely from EUR 259,614 to EUR 36,688,323. For other methods, such as pathogen testing/culturing, use of apheresis instead of whole blood-derived platelets, and storage in platelet additive solution, evidence was sparse. Overall, the quality and applicability of the included studies was limited. CONCLUSIONS Our findings are of interest to decision makers who consider implementing pathogen reduction. For other preparation, storage, selection and dosing methods in platelet transfusion, CE remains unclear due to insufficient and outdated evaluations. Future high-quality research is needed to expand the evidence base and increase our confidence in the findings.
PICO Summary
Population
Platelet transfusion recipients (15 full economic evaluations).
Intervention
Systematic review summarising the available literature regarding the cost effectiveness of different platelet preparation, storage, selection and dosing methods in platelet transfusion.
Comparison
Outcome
Eight studies investigated the costs and health consequences (transfusion-related events, bacterial and viral infections or illnesses) of pathogen reduction. The estimated incremental cost per quality-adjusted life-year varied widely from EUR 259,614 to EUR 36,688,323. For other methods, such as pathogen testing/culturing, use of apheresis instead of whole blood-derived platelets, and storage in platelet additive solution, evidence was sparse. Overall, the quality and applicability of the included studies was limited.
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Pathogen inactivation methods to prevent transfusion-transmissible arboviruses
Giménez-Richarte Á, Ortiz de Salazar MI, Giménez-Richarte MP, Larrea L, Arbona C, Marco P, Ramos-Rincón JM
Tropical medicine & international health : TM & IH. 2023
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Editor's Choice
Abstract
OBJECTIVE Arboviruses are emerging as a relevant threat to transfusion safety. Pathogen inactivation methods may reduce the risk of transmission through transfusion, as long as they meet minimum standards for effectiveness. This study aims to assess the log reduction of viral load achieved with different pathogen inactivation methods, according to the blood product they are used on and the arbovirus targeted. METHODS Systematic literature review and meta-analysis. Searches were conducted in MEDLINE and Embase. The study protocol was registered in PROSPERO CRD42022312061. We selected records reporting the log reduction of viral load achieved with the main pathogen inactivation methods (amotosalen + UVA light [INTERCEPT], riboflavin + UV light [Mirasol], methylene blue + visible light/UVC light [THERAFLEX], solvent detergent, amustaline [INTERCEPT] and PEN110 [Inactine]), applied to any blood product (plasma, platelets, red blood cells or whole blood) and for any arbovirus. The log reduction of viral loads was assessed by obtaining the mean log reduction factor (LRF). We compared and classified the LRF of different techniques using statistical methods. RESULTS We included 59 publications reporting LRF results in 17 arboviruses. For 13 arboviruses, including Chikungunya virus, Dengue virus, West Nile virus, and Zika virus, at least one of the methods achieves adequate or optimal log reduction of viral load - mean LRF ≥4. The LRF achieved with riboflavin + UV light is inferior to the rest of the techniques, both overall and specifically for plasma, platelets preserved in platelet additive solution (PAS)/plasma, and red blood cells/whole blood. The LRF achieved using Mirasol is also lower for inactivating chikungunya virus, dengue virus, and Zika virus. For West Nile virus, we found no significant differences. In plasma, the method that achieves the highest LRF is solvent/detergent; in platelets, THERAFLEX and INTERCEPT; and in red blood cells/whole blood, PEN110 (Inactine). CONCLUSION Not all pathogen inactivation methods achieve the same LRF, nor is this equivalent between the different arboviruses or blood products. Overall, the LRFs achieved using riboflavin + UV light (Mirasol) are inferior to those achieved with the rest of the pathogen inactivation methods. Regarding the others, LRFs vary by arbovirus and blood product. In light of the threat of different arboviruses, blood establishments should have already validated pathogen inactivation methods and be logistically prepared to implement these techniques quickly.
PICO Summary
Population
Whole blood or human blood products from blood donors (59 studies).
Intervention
Systematic literature review and meta-analysis assessing the log reduction of viral load achieved with different pathogen inactivation methods, according to the blood product they were used on and the arbovirus targeted.
Comparison
Outcome
The included studies reported log reduction factor (LRF) results in 17 arboviruses. For 13 arboviruses, including Chikungunya virus, Dengue virus, West Nile virus, and Zika virus, at least one of the methods achieved adequate or optimal log reduction of viral load - mean LRF ≥4. The LRF achieved with riboflavin + UV light was inferior to the rest of the techniques, both overall and specifically for plasma, platelets preserved in platelet additive solution (PAS)/plasma, and red blood cells/whole blood. The LRF achieved using Mirasol was also lower for inactivating Chikungunya virus, Dengue virus, and Zika virus. For West Nile virus, no significant differences were found. In plasma, the method that achieved the highest LRF was solvent/detergent; in platelets, THERAFLEX and INTERCEPT; and in red blood cells/whole blood, PEN110 (Inactine).
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3.
Meta-analysis of bacterial growth characteristics in platelet components: Refining the inputs of a simulation analysis comparing the relative safety of testing strategies
Walker, B. S., Schmidt, R. L., White, S. K., Metcalf, R. A.
Transfusion. 2023
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Editor's Choice
Abstract
BACKGROUND The relative safety of bacterial risk control strategies for platelets that include culture with or without rapid testing has been compared using simulation analysis. A wide range of bacterial lag and doubling times were included. However, published data on growth rates are available and these data have not been synthesized. We conducted a systematic review and meta-analysis to estimate growth rates and used these estimates to refine a comparative safety analysis of bacterial risk control strategies in the FDA guidance STUDY DESIGN AND METHODS Data were extracted from published studies on bacterial growth rates in platelet components during storage. These data were used to estimate the practical range of growth rates. This refined the inputs for a simulation model comparing the safety of the testing strategies. RESULTS In total, 108 growth curves for 11 different aerobic organisms were obtained. Doubling times ranged from 0.8 to 12 h, but the lower 90% range was approximately 1-5 h. The revised comparative safety simulation using the narrower 1-5-h range showed similar rankings to the prior simulation, with 48-h large-volume delayed sampling with 7-day expiration (48C-7) demonstrating the lowest-ranking relative performance at the 10(3) and 10(5) colony forming unit (CFU)/mL exposure thresholds. DISCUSSION This was a two-step study. First, meta-analysis of published data on aerobic bacterial growth rates in stored platelets showed the vast majority of doubling times were 1-5 h. Next, an updated comparative safety simulation yielded similar results to a prior study, with 48C-7 showing the least favorable relative safety performance.
PICO Summary
Population
Recipients of platelet transfusions (12 studies).
Intervention
Systematic review and meta-analysis to estimate growth rates and used these estimates to refine a comparative safety analysis of bacterial risk control strategies in the FDA guidance.
Comparison
Outcome
Data were extracted from published studies on bacterial growth rates in platelet components during storage. These data were used to estimate the practical range of growth rates. This refined the inputs for a simulation model comparing the safety of the testing strategies. In total, 108 growth curves for 11 different aerobic organisms were obtained. Doubling times ranged from 0.8 to 12 h, but the lower 90% range was approximately 1-5 h. The revised comparative safety simulation using the narrower 1-5-h range showed similar rankings to the prior simulation, with 48-h large-volume delayed sampling with 7-day expiration (48C-7) demonstrating the lowest-ranking relative performance at the 10(3) and 10(5) colony forming unit (CFU)/mL exposure thresholds.
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Next Generation Sequencing of Red Blood Cell Antigens in Transfusion Medicine: Systematic Review and Meta-Analysis
Matosinho, C. G. R., Silva, C. G. R., Martins, M. L., Silva-Malta, M. C. F.
Transfusion medicine reviews. 2023;:150776
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Editor's Choice
Abstract
Molecular analysis of blood groups is important in transfusion medicine, allowing the prediction of red blood cell (RBC) antigens. Many blood banks use single nucleotide variant (SNV) based methods for blood group analysis. While this is a well-established approach, it is limited to the polymorphisms included in genotyping panels. Thus, variants that alter antigenic expression may be ignored, resulting in incorrect prediction of phenotypes. The popularization of next-generation sequencing (NGS) has led to its application in transfusion medicine, including for RBC antigens determination. The present review/meta-analysis aimed to evaluate the applicability of the NGS for the prediction of RBC antigens. A systematic review was conducted following a comprehensive literature search in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Studies were selected based on predefined criteria and evaluated using Strengthening the Reporting of Observational studies in Epidemiology guidelines. The characteristics and results of the studies were extracted and meta-analysis was performed to verify the agreement between results from standard molecular methods and NGS. Kell (rs8176058), Duffy (rs2814778, rs12078), or Kidd (rs1085396) alleles were selected as a model for comparisons. Additionally, results are presented for other blood group systems. Of the 864 eligible studies identified, 10 met the inclusion criteria and were selected for meta-analysis. The pooled concordance proportion for NGS compared to other methods ranged from 0.982 to 0.994. The sequencing depth coverage was identified as crucial parameters for the reliability of the results. Some studies reported difficulty in analyzing more complex systems, such as Rh and MNS, requiring the adoption of specific strategies. NGS is a technology capable of predicting blood group phenotypes and has many strengths such as the possibility of simultaneously analyzing hundred individuals and gene regions, and the ability to provide comprehensive genetic analysis, which is useful in the description of new alleles and a better understanding of the genetic basis of blood groups. The implementation of NGS in the routine of blood banks depends on several factors such as cost reduction, the availability of widely validated panels, the establishment of clear quality parameters and access to bioinformatics analysis tools that are easy to access and operate.
PICO Summary
Population
Blood donors and recipients (10 studies).
Intervention
Next-generation sequencing (NGS) for the prediction of red blood cell (RBC) antigens.
Comparison
Other RBC molecular analysis.
Outcome
A meta-analysis was performed to verify the agreement between results from standard molecular methods and NGS. Kell (rs8176058), Duffy (rs2814778, rs12078), or Kidd (rs1085396) alleles were selected as a model for comparisons. The pooled concordance proportion for NGS compared to other methods ranged from 0.982 to 0.994. The sequencing depth coverage was identified as crucial parameters for the reliability of the results. Some studies reported difficulty in analyzing more complex systems, such as Rh and MNS, requiring the adoption of specific strategies.
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5.
Bacterial culture time to detection in platelet components: An evidence synthesis and estimation of detection failures
Walker BS, Schmidt RL, Moore RA, White SK, Fisher MA, Metcalf RA
Transfusion. 2022
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Editor's Choice
Abstract
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.
PICO Summary
Population
Spiked platelets inoculated into bacterial cultures (16 studies).
Intervention
Systematic review to obtain summary estimates of the time to detection (TTD) for the most common contaminating organisms, and to estimate the risk of detection failures.
Comparison
Outcome
Regression analysis was used to estimate TTD for culture bottles at different inoculum sizes. Detection failures were defined as events in which contaminated components were transfused to a patient. Published data was used on time of transfusion to estimate the risk of detection failures in practice. 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, the average TTD for aerobic organisms was 19.2 hours while it was 24.9 hours in anaerobic organisms, but there was substantial overall variation. A hold time of 12 vs. 24 hours had minimal effect for most organisms.
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6.
Economic Analyses of Pathogen-Reduction Technologies in Blood Transfusion: A Systematic Literature Review
LaFontaine PR, Yuan J, Prioli KM, Shah P, Herman JH, Pizzi LT
Applied health economics and health policy. 2021
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Editor's Choice
Abstract
BACKGROUND Technologies used in the processing of whole blood and blood component products, including pathogen reduction, are continuously being adopted into blood transfusion workflows to improve process efficiencies. However, the economic implications of these technologies are not well understood. With the advent of these new technologies and regulatory guidance on bacterial risk-control strategies, an updated systematic literature review on this topic was warranted. OBJECTIVE The objective of this systematic literature review was to summarize the current literature on the economic analyses of pathogen-reduction technologies (PRTs). METHODS A systematic literature review was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines to identify newly published articles in PubMed, MEDLINE Complete, and EconLit from 1 January 2000 to 17 July 2019 related to economic evaluations of PRTs. Only full-text studies in humans published in English were included in the review. Both budget-impact and cost-effectiveness studies were included; common outcomes included cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS The initial searches identified 433 original abstracts, of which 16 articles were included in the final data extraction and reporting. Seven articles presented cost-effectiveness analyses and nine assessed budget impact. The introduction of PRT increased overall costs, and ICER values ranged widely across cost-effectiveness studies, from below $US150,000/QALY to upwards of $US20,000,000/QALY. This wide range of results was due to a multitude of factors, including comparator selection, target patient population, and scenario analyses included. CONCLUSIONS Overall, the results of economic evaluations of bacterial risk-control strategies, regardless of mechanism, were highly dependent on the current screening protocols in place. The optimization of blood transfusion safety may not result in decisions made at the willingness-to-pay thresholds commonly seen in pharmaceutical evaluations. Given the critical public health role of blood products, and the potential safety benefits introduced by advancements, it is important to continue building this body of evidence with more transparency and data source heterogeneity. This updated literature review provides global context when making local decisions for the coverage of new and emerging bacterial risk-control strategies.
PICO Summary
Population
Whole blood and blood component products (16 studies).
Intervention
Systematic review to summarize the current literature on the economic implications of pathogen-reduction technologies (PRTs).
Comparison
Outcome
The introduction of PRT increased overall costs, and incremental cost-effectiveness ratios values ranged widely across cost-effectiveness studies, from below $US150,000/quality-adjusted life-years (QALY), to upwards of $US20,000,000/QALY. This wide range of results was due to a multitude of factors, including comparator selection, target patient population, and scenario analyses.
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Effect of parachute delivery on red blood cell (RBC) and plasma quality measures of blood for transfusion
Bates M, Watts S, Doughty H, Woolley T, Miles A, Barry L, Jenner D, Sedman A, Purcell R, Kirkman E
Transfusion. 2021;61 Suppl 1:S223-s233
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Editor's Choice
Abstract
BACKGROUND Parachute airdrop offers a rapid transfusion supply option for humanitarian aid and military support. However, its impact on longer-term RBC survival is undocumented. This study aimed to determine post-drop quality of RBCs in concentrates (RCC), and both RBCs and plasma in whole blood (WB) during subsequent storage. STUDY DESIGN AND METHODS Twenty-two units of leucodepleted RCC in saline, adenine, glucose, mannitol (SAGM) and 22 units of nonclinical issue WB were randomly allocated for air transportation, parachute drop, and subsequent storage (parachute), or simply storage under identical conventional conditions (4 ± 2°C) (control). All blood products were 6-8 days post-donation. Parachute units were packed into Credo Cubes, (Series 4, 16 L) inside a PeliCase (Peli 0350) and rigged as parachute delivery packs. Packs underwent a 4-h tactical flight (C130 aircraft), then parachuted from 250 to 400 ft before ground recovery. The units were sampled aseptically before and after airdrop at weekly intervals. A range of assays quantified the RBC storage lesion and coagulation parameters. RESULTS Blood units were maintained at 2-6°C and recovered intact after recorded ground impacts of 341-1038 m s(-2) . All units showed a classical RBC storage lesion and increased RBC microparticles during 42 days of storage. Fibrinogen and clotting factors decreased in WB during storage. Nevertheless, no significant difference was observed between Control and Parachute groups. Air transportation and parachute delivery onto land did not adversely affect, or shorten, the shelf life of fresh RBCs or WB. DISCUSSION Appropriately packaged aerial delivery by parachute can be successfully used for blood supply.
PICO Summary
Population
Units of red cells and whole blood (WB), (n= 44).
Intervention
Air transportation, parachute drop, and subsequent storage (Parachute, (n= 24).
Comparison
Storage under identical conventional conditions (Control, n= 20).
Outcome
Blood units were maintained at 2-6°C and recovered intact after recorded ground impacts of 341-1038 m s-2. All units showed a classical red blood cell (RBC) storage lesion and increased RBC micro particles during 42 days of storage. Fibrinogen and clotting factors decreased in whole blood during storage. Nevertheless, no significant difference was observed between Control and Parachute groups. Air transportation and parachute delivery onto land did not adversely affect, or shorten, the shelf life of fresh RBCs or WB.
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Randomized controlled trial of 7, 28, vs 42 day stored red blood cell transfusion on oxygen delivery (VO(2) max) and exercise duration
Bennett-Guerrero E, Rizwan S, Rozensky R, Romeiser JL, Brittelli J, Makaryus R, Lin J, Galanakis DK, Triulzi DJ, Moon RE
Transfusion. 2020
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Editor's Choice
Abstract
BACKGROUND Few studies have rigorously assessed the impact of red blood cell (RBC) transfusion on oxygen delivery. Several large trials demonstrated no clinical outcome differences between transfusion of shorter-storage vs prolonged-storage RBCs. These trials did not directly assess functional measures of oxygen delivery. Therefore, it is not clear if 42-day stored RBCs deliver oxygen as effectively as 7-day stored RBCs. STUDY DESIGN AND METHODS Leukocyte-reduced RBCs were collected by apheresis in AS-3. Thirty subjects were randomized (1:1:1) to receive 2 units of autologous RBCs at either 7, 28, or 42 days following donation. VO(2) max testing, using a standardized protocol to exhaustion, was performed 2 days before (Monday) and 2 days after (Friday) the transfusion visit (Wednesday). The primary endpoint was the percent increase in VO(2) max between Monday and Friday. The secondary endpoint was the percent change in duration of exercise for the same time points. RESULTS Hemoglobin levels decreased by 2.8 ± 1.4 g/dL after donation and increased by 2.1 ± 0.6 g/dL after transfusion. This change in hemoglobin was associated with expected decreases (then increases after transfusion) in VO(2) max and exercise duration. No differences were observed between 7-day and 42-day RBC transfusion for percent increase in median [IQR] VO(2) max (10.5 [0.2-17.3] vs 10.9 [5.7-16.8], P = .41) or for percent increase in exercise duration (5.4 [4.1-6.9] vs 4.9 [2.0-7.2], P = .91), respectively. Results were similar for 28-day RBCs and were consistent across the ITT and per-protocol analysis populations. CONCLUSION These data indicate that 42-day, 28-day, and 7-day RBCs have similar ability to deliver oxygen.
PICO Summary
Population
Blood donors (n= 30).
Intervention
2 units of autologous red blood cells (RBCs) at 7 days following donation (n= 10).
Comparison
2 units of autologous RBCs at either 28 days (n= 10), or 42 days following donation (n= 10).
Outcome
Haemoglobin levels decreased by 2.8 ± 1.4 g/dL after donation and increased by 2.1 ± 0.6 g/dL after transfusion. This change in haemoglobin was associated with expected decreases (then increases after transfusion) in VO(2) max and exercise duration. No differences were observed between 7-day and 42-day RBC transfusion for percent increase in median [IQR] VO(2) max (10.5 [0.2-17.3] vs 10.9 [5.7-16.8]) or for percent increase in exercise duration (5.4 [4.1-6.9] vs 4.9 [2.0-7.2]), respectively. Results were similar for 28-day RBCs and were consistent across the ITT and per-protocol analysis populations.
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9.
Quality assessment of red blood cell suspensions derived from pathogen-reduced whole blood
Kumukova I, Trakhtman P, Starostin N, Borsakova D, Ignatova A, Bayzyanova Y
Vox sanguinis. 2020
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Editor's Choice
Abstract
BACKGROUND We used laboratory indicators to evaluate the quality of pathogen-reduced red blood cell suspension (RBCS) compared with gamma-irradiated RBCS. MATERIALS AND METHODS To determine biochemical and metabolic parameters of RBCS, we obtained 50 whole blood units from healthy volunteers and randomized them into 2 groups: 25 were pathogen-reduced, and then, RBCS prepared from them. RBCS from the other 25 was gamma-irradiated. Sampling was carried out on day zero before and after treatment and at 7, 14, 21 and 28 days. To determine lymphocyte inactivation, we collected another 35 whole blood units. Each was sampled to form 3 study groups: untreated, gamma-irradiated and pathogen-reduced. Daily sampling was carried out during 3 days of storage. RESULTS The quality of RBCS from both groups was largely the same, except for haemolysis and red blood cell fragility, which were more pronounced in the pathogen-reduced group. This finding limited the shelf life of pathogen-reduced RBCS to 14 days. Lymphocyte viability was significantly reduced after both treatments. Proliferation of lymphocytes after pathogen reduction was reduced to the detection limit, while low-level proliferation was observed in gamma-irradiated samples. CONCLUSION Pathogen-reduced red blood cells have acceptable quality and can be used for transfusion within 14 days. Results of inactivation of lymphocytes demonstrate that pathogen reduction technology, applied on WB, can serve as an alternative to irradiation.
PICO Summary
Population
Whole blood units from healthy donors (n= 50).
Intervention
Pathogen-reduction with riboflavin and ultraviolet light (n= 25).
Comparison
Gamma‐irradiation (n= 25).
Outcome
The quality of RBCS from both groups was largely the same, except for haemolysis and red blood cell fragility, which were more pronounced in the pathogen-reduced group. This finding limited the shelf life of pathogen-reduced RBCS to 14 days.