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.

Abstract

OBJECTIVE Most of the previous studies of drone transport of blood samples examined normal blood samples transported under tranquil air conditions. We studied the effects of 1- and 2-hour drone flights using random vibration and turbulence simulation (10-30 g-force) on blood samples from 16 healthy volunteers and 74 patients with varying diseased. METHODS Thirty-two of the most common analytes were tested. For biochemical analytes, we used plasma collected in lithium heparin tubes with and without separator gel. Gel samples were analyzed for the effect of separation by centrifugation before or after turbulence. Turbulence was simulated in an LDS V8900 high-force shaker using random vibration (range, 5-200 Hz), with samples randomly allocated to 1- or 2-hour flights with 25 or 50 episodes of turbulence from 10 to 30 G. RESULTS For all hematologic and most biochemical analytes, test results before and after turbulence exposure were similar (bias < 12%, intercepts < 10%). However, aspartate aminotransferase, folate, lactate dehydrogenase and lipid index increased significantly in samples separated by gel and centrifugation prior to vibration and turbulence test. These changes increased form 10 G to 30 G, but were not observed when the samples were separated after vibration and turbulence. CONCLUSIONS Whole blood showed little vulnerability to turbulence, whereas plasma samples separated from blood cells by gel may be significantly influenced by turbulence when separated by spinning before the exposure. Centrifugation of plasma samples collected in tubes with separator gel should be avoided before drone flights that could be subject to turbulence.

Abstract

BACKGROUND AND OBJECTIVES Filariae are parasitic worms that include the pathogens Loa loa, Onchocerca volvulus, Wuchereria bancrofti, Brugia spp. and Mansonella spp. which are endemic in parts of Africa, Asia, Asia-Pacific, South and Central America. Filariae have a wide clinical spectrum spanning asymptomatic infection to chronic debilitating disease including blindness and lymphedema. Despite successful eradication programmes, filarial infections remain an important -albeit neglected - source of morbidity. We sought to characterize the risk of transfusion transmission of microfilaria with a view to guide mitigation practices in both endemic and non-endemic countries. MATERIALS AND METHODS A scoping review of scientific publications as well as grey literature was carried out by a group of domain experts in microbiology, transfusion medicine and infectious diseases, representing the parasite subgroup of the International Society of Blood Transfusion. RESULTS Cases of transfusion-transmitted filariasis are rare and confined to case reports of variable quality. Transfusion-associated adverse events related to microfilariae are confined to isolated reports of transfusion reactions. Serious outcomes have not been reported. No known strategies have been implemented, specifically, to mitigate transfusion-transmitted filariasis yet routine blood donor screening for other transfusion-transmissible infections (e.g. hepatitis B, malaria) may indirectly defer donors with microfilaremia in endemic areas. CONCLUSION Rare examples of transfusion-transmitted filariasis, without serious clinical effect, suggest that filariasis poses low transfusion risk. Dedicated mitigation strategies against filarial transfusion transmission are not recommended. Given endemicity in low-resource regions, priority should be on the control of filariasis with public health measures.

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.

Abstract

BACKGROUND Source plasma is essential to support the growing demand for plasma-derived medicinal products. Supply is short, with donor availability further limited by the COVID-19 pandemic. This study examined whether a novel, personalized, technology-based nomogram was non-inferior with regard to significant hypotensive adverse events (AEs) in healthy donors. STUDY DESIGN AND METHODS IMPACT (IMproving PlasmA CollecTion) was a prospective, multi-center, double-blinded, randomized, controlled trial carried out between January 6 and March 26, 2020 in three U.S. plasma collection centers. Donors were randomized to the current simplified 1992 nomogram (control) or a novel Percent Plasma Nomogram (PPN) with personalized target volume calculation (experimental). Primary endpoint was the rate of significant hypotensive AEs. Non-inferiority (NI) was tested with a margin of 0.15%. Collected plasma volume was a secondary endpoint. RESULTS 3,443 donors (Mean [SD] BMI: 32 (7.74) kg/m(2) ; 65% male) underwent 23,137 donations (Median [range]: 6 [1-22] per subject). Ten significant hypotensive AEs were observed (6 control; 4 experimental), with model-based AE incidence rate estimates (95% CI) of 0.051% (0.020%, 0.114%) and 0.035% (0.010%, 0.094%), respectively (p=0.58). NI was met at an upper limit of 0.043% versus the predefined margin of 0.15%. There was no statistical difference between total AE (all AE types: p=0.32). Mean plasma volume collected was 777.8 mL (control) versus 841.7 mL (experimental); an increase of 63.9 mL per donation (8.2%; p<0.0001). CONCLUSION This trial showed that a novel personalized nomogram approach in healthy donors allowed approximately 8% more plasma per donation to be collected without impairing donor safety. This article is protected by copyright. All rights reserved.

Abstract

Emergency surgical treatment has been challenging and the risk of blood contamination has been high, which is a concern among the medical and dental fraternity. The risk outweighs the benefits in these unprecedented times if proper screening and inactivation of blood products are not performed. Pathogen reduction technologies incorporate various modalities for the inactivation of blood products mainly related to blood transfusion. Oral surgical procedures and periodontal surgeries use platelet-rich fibrin for various regenerative procedures that amplify the prognosis positively. The use of blood products for various treatments could result in contamination, a factor which should be significant attention. The objective of this study was to review the role of pathogen reduction technology in inactivating pathogens in blood products and its use in oral and periodontal surgical procedures. The literature presented in the study is from original studies from a period of 2000 to 2020 which was sourced from Medline, PubMed, and Cochrane central databases. Relevant published papers and in-press papers that provided information were identified and selected. The studies presented have shown data related to implementation of pathogen reduction technologies in relation to the severe acute respiratory syndrome, Middle East respiratory syndrome, and its possible implementation in coronavirus disease-2019 (COVID-19). The paper reviews the various technologies offered and the possibility to eradicate pathogens found in routine blood products, used in oral and periodontal surgical procedures. In all probability, the use of pathogen reduction technology might offer a ray of light to contain the spread among dental treatment procedures.

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.

Abstract

BACKGROUND Single donor apheresis platelets are superior in quality, but their usage is limited in a developing country due to cost and time constraints. Hence the product obtained must exceed in terms of yield, donor safety and technical convenience. Previous literature available on cell separators is on older versions. AIMS Prospective comparison of 5 latest cell separators (AmiCORE, COM.TEC, Haemonetics MCS+, SpectraOptia and TrimaAccel) for product yield, performance variables and donor adverse effects. MATERIAL & METHODS From October 2019 - March 2020, 1108 donors were randomly allotted to a cell separator. Post-donation sample was taken from the donor 15-20 minutes after procedure completion. The platelet yield from the product collected was measured twice (day 0 and day 1). Donor demography, pre-and post-procedural donor peripheral blood values, performance and product variables were statistically analyzed. RESULTS AmiCORE had an optimal collection efficacy (44.6%) and collection rate (0.037 x 1011/minute). Haemonetics MCS+ had a better collection efficacy (48.4%) and rate (0.038 x 1011/minute). Spectra Optia achieved least procedural time (59.5 minutes), donor adverse effects (6.3%); highest collection efficacy (52.8%) and rate (0.056 x 1011/minute). Trima Accel achieved highest collection rate (0.056 x 1011/minute) and the least product volume (228 ml). CONCLUSION Highest collection efficacy was achieved by Trima Accel, highest collection rate by Trima Accel and Spectra Optia, lowest donor adverse effects by Spectra Optia and least number of procedural troubleshooting by COM.TEC. Apart from this, fiscal factors and service availability also need to be considered before choosing a cell separator.

Abstract

INTRODUCTION Platelet-rich plasma is widely used for different types of clinical situations, but universal standardization of procedures for its preparation is still lacking. METHODS Scoping review of comparative studies that have assessed at least two alternatives in one or more stages of preparation, storage and/or administration of PRP or its related products. A systematic search was conducted in MEDLINE, Embase, and LILACS. Two authors screened references independently. Data extraction was performed iteratively, and results were presented for each included comparison. RESULTS Thirty-nine studies were included after assessing full texts, focusing on the comparison of PRP to a related product, types of anticoagulants, centrifugation protocols, commercial kits, processing time, methods for activation, and application concomitantly to other substances. Only laboratory outcomes were assessed, as platelet, leukocyte and growth factor concentrations. CONCLUSION Results showed great variability related to methods employed in different stages of PRP processing, which may explain the variability observed in clinical trials assessing the efficacy of PRP for different clinical situations.

Abstract

BACKGROUND Primary culture alone was a bacterial risk control strategy intended to facilitate interdiction of contaminated platelets (PLTs). A September 2019 FDA guidance includes secondary testing options to enhance safety. Our objective was to use meta-analysis to determine residual contamination risk after primary culture using secondary culture and rapid testing. STUDY DESIGN AND METHODS A December 2019 literature search identified articles on PLT bacterial detection rates using primary culture and a secondary testing method. We used meta-analysis to estimate secondary testing detection rates after a negative primary culture. We evaluated collection method, sample volume, sample time, and study date as potential sources of heterogeneity. RESULTS The search identified 6102 articles; 16 were included for meta-analysis. Of these, 12 used culture and five used rapid testing as a secondary testing method. Meta-analysis was based on a total of 103 968 components tested by secondary culture and 114 697 by rapid testing. The residual detection rate using secondary culture (DR(SC) ) was 0.93 (95% CI, 0.24-0.6) per 1000 components, while residual detection rate using rapid testing (DR(RT) ) was 0.09 (95% CI, 0.01-0.25) per 1000 components. Primary culture detection rate was the only statistically significant source of heterogeneity. CONCLUSION We evaluated bacterial detection rates after primary culture using rapid testing and secondary culture. These results provide a lower and upper bound on real-world residual clinical risk because these methods are designed to detect high-level exposures or any level of exposure, respectively. Rapid testing may miss some harmful exposures and secondary culture may identify some clinically insignificant exposures.