Patterns of red blood cell utilization: Harnessing electronic health records data from the Information Standard for Blood and Transplant (ISBT) 128 system within the Biologics Effectiveness and Safety (BEST) initiative.

BACKGROUND: Current hemovigilance methods generally rely on survey data or administrative claims data utilizing billing and revenue codes, each of which has limitations. We used electronic health records (EHR) linked to blood bank data to comprehensively characterize red blood cell (RBC) utilization patterns and trends in three healthcare systems participating in the U.S. Food and Drug Administration Center for Biologics Evaluation and Research Biologics Effectiveness and Safety (BEST) initiative. METHODS: We used Information Standard for Blood and Transplant (ISBT) 128 codes linked to EHR from three healthcare systems data sources to identify and quantify RBC-transfused individuals, RBC transfusion episodes, transfused RBC units, and processing methods per year during 2012-2018. RESULTS: There were 577,822 RBC units transfused among 112,705 patients comprising 345,373 transfusion episodes between 2012 and 2018. Utilization in terms of RBC units and patients increased slightly in one and decreased slightly in the other two healthcare facilities. About 90% of RBC-transfused patients had 1 (~46%) or 2-5 (~42%)transfusion episodes in 2018. Among the small proportion of patients with ≥12 transfusion episodes per year, approximately 60% of episodes included only one RBC unit. All facilities used leukocyte-reduced RBCs during the study period whereas irradiated RBC utilization patterns differed across facilities. DISCUSSION: ISBT 128 codes and EHRs were used to observe patterns of RBC transfusion and modification methods at the unit level and patient level in three healthcare systems participating in the BEST initiative. This study shows that the ISBT 128 coding system in an EHR environment provides a feasible source for hemovigilance activities.

Cord blood beyond transplantation: can we use the experience to advance all cell therapies?

Unrelated cord blood (CB) units, already manufactured, fully tested and stored, are high-quality products for haematopoietic stem cell transplantation and cell therapies, as well as an optimal starting material for cell expansion, cell engineering or cell re-programming technologies. CB banks have been pioneers in the development and implementation of Current Good Manufacturing Practices for cell-therapy products. Sharing their technological and regulatory experience will help advance all cell therapies, CB-derived or not, particularly as they transition from autologous, individually manufactured products to stored, 'off-the shelf' treatments. Such strategies will allow broader patient access and wide product utilisation.

Cold storage of platelets in platelet additive solution maintains mitochondrial integrity by limiting initiation of apoptosis-mediated pathways.

BACKGROUND: Cold storage of platelets in plasma maintains hemostatic function and is an attractive alternative to room temperature platelets (RTPs). We have recently shown that functional differences between cold-stored platelets (CSPs) and RTPs after 5-day storage are associated with mitochondrial respiration and that CSPs in platelet (PLT) additive solution (PAS) can maintain hemostatic function for at least 15 days. STUDY DESIGN AND METHODS: This study tested the hypothesis that cold storage in PAS preserves mitochondrial integrity by reducing PLT apoptosis. CSPs and RTPs in plasma or PAS were stored and assayed for up to 15 days for mitochondrial function and integrity, mitochondrial-associated mRNA transcript expression, apoptotic proteins, and apoptotic flow cytometry metrics. RESULTS: CSP preserved mitochondria-associated mRNA comparable to baseline levels, improved mitochondrial respiration, and minimized depolarization to Day 15. Additionally, CSPs had minimal induction of caspases, preservation of plasma membrane integrity, and low expression of pro-apoptotic Bax. Storage in PAS appeared to be protective for RTPs in some parameters and enhanced the effects of CSPs. CONCLUSION: Mitochondrial function and molecular analyses defined CSP priming as distinctly different from the well-documented RTP storage lesion. While current blood bank storage at room temperature is limited to 5 to 7 days, refrigeration and storage in PAS for up to 15 days may represent an opportunity to enhance inventories and access to PLT hemostatic support for bleeding patients.

Effects of Intercept pathogen reduction treatment on extended cold storage of apheresis platelets.

BACKGROUND: Platelets pose the greatest transfusion-transmitted infectious risk among blood products. Refrigeration of platelets can mitigate bacterial contamination and extend platelet shelf life. Implementation of pathogen reduction technologies (PRTs) at blood banks has become increasingly popular to protect against emerging and reemerging infectious diseases. In this study, we sought to evaluate the effects of Intercept PRT on platelets collected on different platforms and cold-stored for up to 21 days in plasma and platelet additive solution (PAS). METHODS: Double-dose apheresis platelets were collected with use of a Trima or Amicus system into either 100% plasma or 65% InterSol PAS/35% plasma and split equally between two bags. One bag served as control, while the other received Intercept PRT treatment. Bags were stored unagitated in the cold and evaluated on Days 1, 7, 14, and 21 to assess platelet metabolism, activation, aggregation, and clot formation and retraction. RESULTS: By Day 14 of storage, lactate levels reached approximately 13 mmol/L for all samples irrespective of Intercept treatment. Mean clot firmness dropped from the 62.2- to 67.5-mm range (Day 1) to the 28.4- to 51.3-mm range (Day 21), with no differences observed between groups. Clot weights of Intercept-treated Trima/plasma samples were significantly higher than control by Day 14 of storage (P = .004), indicating a reduced clot retraction function. Intercept treatment caused a higher incidence of plasma membrane breakdown in plasma-stored platelets (P = .0013; Trima/plasma Day 14 Control vs Intercept). CONCLUSIONS: Intercept treatment of platelets and subsequent cold storage, in plasma or PAS, results in comparable platelet metabolism platelets for up to 14 days of storage but altered clotting dynamics. Pathogen-reduced platelets with an extended shelf life would be beneficial for the deployed setting and would greatly impact transfusion practice among civilian transfusion centers.

Transfusion medicine and blood banking education and training for blood establishment laboratory staff: A review of selected countries in Africa.

BACKGROUND: Avoidable human error is a significant cause of transfusion adverse events. Adequately trained, laboratory staff in blood establishments and blood banks, collectively blood facilities, are key in ensuring high-quality transfusion medicine (TM) services. Gaps in TM education and training of laboratory staff exist in most African countries. We assessed the status of the training and education of laboratory staff working in blood facilities in Africa. STUDY DESIGN AND METHODS: A cross-sectional study using a self-administered pilot-tested questionnaire was performed. The questionnaire comprised 26 questions targeting six themes. Blood facilities from 16 countries were invited to participate. Individually completed questionnaires were grouped by country and descriptive analysis performed. RESULTS: Ten blood establishments and two blood banks from eight African countries confirmed the availability of a host of training programs for laboratory staff; the majority of which were syllabus or curriculum-guided and focused on both theoretical and practical laboratory skills development. Training was usually preplanned, dependent on student and trainer availability and delivered through lecture-based classroom training as well as formal and informal on the job training. There were minimal online didactic and self-directed learning. Teaching of humanistic values appeared to be lacking. CONCLUSION: We confirmed the availability of diverse training programs across a variety of African countries. Incorporation of virtual learning platforms, rather than complete reliance on didactic, in-person training programs may improve the education reach of the existing programs. Digitalization driven by the coronavirus disease 2019 pandemic may provide an opportunity to narrow the knowledge gap in low- and middle-income countries (LMICs).

New blood donors in times of crisis: Increased donation willingness, particularly among people at high risk for attracting SARS-CoV-2.

BACKGROUND: Traditionally, during crises the number of new blood donors increases. However, the current coronavirus disease 2019 (COVID-19) pandemic created additional barriers to donate due to governmental prevention measures and increased personal health risks. In this report, we examined how the pandemic affected new donor registrations in the Netherlands, especially among groups with higher risk profiles for severe COVID-19. Additionally, we explored the role of media for blood donation and new donor registrations. STUDY DESIGN AND METHODS: We analyzed new donor registrations and attention for blood donation in newspapers and on social media from January until May 2020, in comparison to the same period in 2017 to 2019. RESULTS: After the introduction of nationwide prevention measures, several peaks in new donor registrations occurred, which coincided with peaks in media attention. Interestingly, people with a higher risk profile for COVID-19 (e.g., due to age or region of residence) were overrepresented among new registrants. DISCUSSION: In sum, the first peak of the current pandemic has led to increased new blood donor registrations, despite the associated increased health risks. Time and future studies will have to tell whether these new donors are one-off 'pandemic' donors or if they will become regular, loyal donors.

Blood supply management in times of SARS-CoV-2 pandemic - challenges, strategies adopted, and the lessons learned from the experience of a hospital-based blood centre.

INTRODUCTION: Numerous concerns regarding maintenance of blood inventory have been raised after SARS-CoV-2 pandemic outbreak. These concerns were based on the experience of blood centres in previous pandemics where shortage of blood components was reported. The present study had tried to understand the impact of SARS-CoV-2 pandemic on blood collection and demand as well as the impact of disaster planning in maintaining an adequate inventory. METHODS: Data related to blood supply and demand were collected retrospectively using blood bank management software for pre-COVID-19 and COVID-19 time period and compared. Strategies adopted and effects of changes in existing disaster plans to maintain an adequate inventory were studied. RESULTS: A drastic fall in the red cell inventory was observed as compared to pre-COVID-19 time period was observed due to disproportionate decrease in blood collection (1/6 to 1/9 of the previous collection) and demand (1/2 of the previous demand). The buffer stock fell gradually over a period of three weeks with cancellation of planned blood donation drives. A buffer stock equivalent to 2-week inventory led to adequate inventory in the initial lockdown periods. Similar fall was observed in the platelet inventory with reduction in the blood collection but almost a proportionate reduction in the platelet demand led to adequate inventory. No increase in wastage was observed for both red cells and platelets during this period. DISCUSSION: A buffer stock of blood and blood components, strict adherence to the transfusion triggers, good coordination with the clinical staff and a prospective review of blood transfusion requests to ensure rational blood transfusion were some of the steps which helped us to successfully maintain transfusion requirements in the initial phases of the COVID-19 pandemic. Use of first-in-first-out policy prevented any wastage due to outdating of blood.

Transfusion Safety Officers in the United States: Survey of characteristics and approaches to implementation.

BACKGROUND: Transfusion safety officers (TSO) function as liaisons between the blood bank and clinical staff, utilizing audits, quality improvement, reviews, communication, education, and general vigilance to enhance transfusion safety. While hospitals in Europe and Canada have long employed TSOs, a majority of institutions in the United States (US) have yet to implement this resource, despite the mounting evidence to support their effectiveness. STUDY DESIGN AND METHODS: An anonymous 20-question survey was administered to 104 hospitals with valid email contact information. Survey questions addressed the presence of a TSO, characteristics, backgrounds, and education of TSOs, the reporting and funding structure of the position, and role responsibilities. RESULTS: 53 responses were received, with 52 surveys completed (51 % response rate). The majority of responding institutions have a patient blood management (PBM) program (n = 40, 77 %) and 33 (63 %) have at least 1 TSO. 61 % of TSOs report an educational background in nursing, with 11 additional unique training backgrounds identified. TSO responsibilities are varied and include quality improvement, education, transfusion safety event analysis, and participation in PBM initiatives. Barriers to implementing a TSO position include lack of resources, financial impediments, and a lack of understanding of the position and its value by administrators and clinicians. DISCUSSION: The results of this survey highlight how TSOs contribute to transfusion safety and PBM and may provide guidance to hospitals interested in implementing a TSO position. It also elucidates the range of TSO responsibilities and approaches that institutions utilize to advocate for, and implement, this position in the US.

Triage tool for the rationing of blood for massively bleeding patients during a severe national blood shortage: guidance from the National Blood Transfusion Committee.

The emerging COVID-19 pandemic has overwhelmed healthcare resources worldwide, and for transfusion services this could potentially result in rapid imbalance between supply and demand due to a severe shortage of blood donors. This may result in insufficient blood components to meet every patient's needs resulting in difficult decisions about which patients with major bleeding do and do not receive active transfusion support. This document, which was prepared on behalf of the National Blood Transfusion Committee in England, provides a framework and triage tool to guide the allocation of blood for patients with massive haemorrhage during severe blood shortage. Its goal is to provide blood transfusions in an ethical, fair, and transparent way to ensure that the greatest number of life years are saved. It is based on an evidence- and ethics-based Canadian framework, and would become operational where demand for blood greatly exceeds supply, and where all measures to manage supply and demand have been exhausted. The guidance complements existing national shortage plans for red cells and platelets.

Optimizing blood bank resources when implementing a low-titer group O+ whole blood program: an in silico study.

INTRODUCTION: Low-titer group O+ whole blood (LTOWB) is becoming commonly used in massive bleeding resuscitation, but the impact on blood center O+ RBCs has not been studied. This in silico model simulated a variety of different LTOWB production and utilization patterns. METHODS: Collections and distributions data from a large blood collector were scaled to vary the total number of O+ red blood cell (RBC) collections, the O+ RBC collection: import ratio, and the O+ RBC apheresis: whole blood (WB) collection ratio. Daily LTOWB demand was determined by the daily number of LTOWB recipients, average number of LTOWB units transfused per patient, maximum number of LTOWB units a single patient can receive, and seasonality of LTOWB use. LTOWB program factors included the high-titer exclusion %, the LTOWB expiry, and whether LTOWB units were reclaimed as O+ RBC units on the date of expiry. Simulations using unique combinations of the above input parameters were performed. RESULTS: For the 1,224,720 unique combinations of input parameters simulated, the average increase in the fraction of additional O+ RBC units required to meet hospital demand was only 0.02%. Higher daily LTOWB demand resulted in more LTOWB shortages. Increasing the minimum LTOWB inventory threshold reduced LTOWB shortages without increasing the number of required additional RBC units. LTOWB wastage was minimal but was lower with longer LTOWB shelf life or manufacture of RBC units from unused LTOWB on Day 14. CONCLUSION: Implementing an LTOWB program does not have a major impact on the blood collectors' needs for additional RBC units to meet hospital demands.

Zika virus and its implications on cord blood banking and transplantation.

Umbilical cord blood is an important cellular therapy product used for hematopoietic stem cell transplantation, but the US Food and Drug Administration guidance regarding donor screening to reduce the risk of Zika transmission has decreased the number of licensed, eligible cord blood units available for transplantation. There is a crucial need for updated travel risk assessment for Zika virus transmission, validated screening tests for Zika virus in umbilical cord blood, and further research on Zika virus transmissibility due to umbilical cord blood products to ensure that umbilical cord blood and related tissues are safe and available for transplantation.

Development of a flow standard to enable highly reproducible measurements of deformability of stored red blood cells in a microfluidic device.

BACKGROUND: Great deformability allows red blood cells (RBCs) to flow through narrow capillaries in tissues. A number of microfluidic devices with capillary-like microchannels have been developed to monitor storage-related impairment of RBC deformability during blood banking operations. This proof-of-concept study describes a new method to standardize and improve reproducibility of the RBC deformability measurements using one of these devices. STUDY DESIGN AND METHODS: The rate of RBC flow through the microfluidic capillary network of the microvascular analyzer (MVA) device made of polydimethylsiloxane was measured to assess RBC deformability. A suspension of microbeads in a solution of glycerol in phosphate-buffered saline was developed to be used as an internal flow rate reference alongside RBC samples in the same device. RBC deformability and other in vitro quality markers were assessed weekly in six leukoreduced RBC concentrates (RCCs) dispersed in saline-adenine-glucose-mannitol additive solution and stored over 42 days at 4°C. RESULTS: The use of flow reference reduced device-to-device measurement variability from 10% to 2%. Repeated-measure analysis using the generalized estimating equation (GEE) method showed a significant monotonic decrease in relative RBC flow rate with storage from Week 0. By the end of storage, relative RBC flow rate decreased by 22 ± 6% on average. CONCLUSIONS: The suspension of microbeads was successfully used as a flow reference to increase reproducibility of RBC deformability measurements using the MVA. Deformability results suggest an early and late aging phase for stored RCCs, with significant decreases between successive weeks suggesting a highly sensitive measurement method.

The effect of entrustable professional activities on pathology resident confidence in blood banking/transfusion medicine.

BACKGROUND: The Accreditation Council for Graduate Medical Education requires milestone reporting of the Six General Core Competencies. Additionally, Graduate Medical Education (GME) is transitioning to adopt competency-based education methodologies including entrustable professional activities (EPAs) for objective, observable, and measurable milestone progression. The College of American Pathologists published 19 EPAs, including one for transfusion-related adverse events. This survey study includes developing EPAs for transfusion reaction evaluation and assessing residents before and after implementing these EPAs. STUDY DESIGN AND METHODS: Three transfusion reaction EPAs were developed and implemented in July 2018 for the Postgraduate Year (PGY) 2 pathology residents. An online, anonymous survey was sent to all 21 pathology trainees before and one year after EPA implementation. In July 2018 and August 2019, each survey included the same six multiple-choice, single-response, confidence questions, with a rating scale of extremely, very, slightly, or not at all confident. This study was approved by the hospital's Institutional Review Board for Health Sciences Research and GME Committee. RESULTS: Analysis was performed on PGY2-4 residents. In 2018, 13 of 20 participants were analyzed. In 2019, 15 of 19 participants were analyzed. Number and percentage of responses were reported. The results showed an increase in trainee confidence, with the greatest improvement among the first class to use the EPAs. CONCLUSION: EPAs provide an effective framework for objective and measurable progression of trainees. One year after the implementation of transfusion reaction EPAs at our site, the trainees showed enhanced confidence levels in handling Blood Bank and Transfusion Medicine Services coverage.

Financial analysis of large-volume delayed sampling to reduce bacterial contamination of platelets.

BACKGROUND: Effective and financially viable mitigation approaches are needed to reduce bacterial contamination of platelets in the US. Expected costs of large-volume delayed sampling (LVDS), which would be performed by a blood center prior to shipment to a hospital, were compared to those of pathogen reduction (PR), point-of-release testing (PORt), and secondary bacterial culture (SBC). METHODS: Using a Markov-based decision-tree model, the financial and clinical impact of implementing all variants of LVDS, PR, PORt, and SBC described in FDA guidance were evaluated from a hospital perspective. Hospitals were assumed to acquire leukoreduced apheresis platelets, with LVDS adding $30 per unit. Monte Carlo simulations were run to estimate the direct medical costs for platelet acquisition, testing, transfusion, and possible complications associated with each approach. Input parameters, including test sensitivity and specificity, were drawn from existing literature and costs (2018US$) were based on a hospital perspective. A one-way sensitivity analysis varied the assumed additional cost of LVDS. RESULTS: Under an approach of LVDS (7-day), the total cost per transfused unit is $735.78, which falls between estimates for SBC (7-day) and PORt. Assuming 20,000 transfusions each year, LVDS would cost $14.72 million annually. Per-unit LVDS costs would need to be less than $22.32 to be cheaper per transfusion than all other strategies, less than $32.02 to be cheaper than SBC (7-day), and less than $196.19 to be cheaper than PR (5-day). CONCLUSIONS: LVDS is an effective and cost-competitive approach, assuming additional costs to blood centers and associated charges to hospitals are modest.

-80 °C deep frozen erythrocytes during military operations. The Dutch frozen concept.

The Dutch military uses frozen blood products for the treatment of bleeding trauma patients during military deployments. With -80 °C frozen blood products it is possible to follow operational demand while reducing the number of resupply transports and loss of products due to expiration. In this paper lessons learned are described on efficient blood management with -80 °C deep-frozen erythrocytes (DEC).

Quality control in veterinary blood banks: evaluation of canine platelet concentrates stored for five days.

BACKGROUND: Platelets undergo structural, biochemical and functional alterations when stored, and platelet storage lesions reduce platelet function and half-life after transfusion. The objective of this study was to evaluate stored canine platelet concentrates with platelet aggregation, flow cytometry and biochemistry assays. Twenty-two bags of canine platelet concentrates were obtained by the platelet-rich plasma method and were assessed on days 1, 3 and 5 after collection. Parameters such as platelet counts, residual leukocytes, platelet swirling, glucose, lactate, pH, CD62P expression (platelet activation), JC-1 (mitochondrial function) and annexin V (apoptosis and cell death) were assessed. RESULTS: Over the five days of storage there was a significant decrease in glucose, HCO3, pCO2, ATP, pH, swirling and mitochondrial function, associated with a significant increase in lactate levels and pO2. At the end of storage pH was 5.9 ± 0.6 and lactate levels were 2.8 ± 1.2 mmol/L. Results of the quality parameters evaluated were similar to those reported in human platelets studies. The deleterious effects of storage were more pronounced in bags with higher platelet counts (> 7.49 × 1010/unit), suggesting that canine platelet concentrates should not contain an excessive number of platelets. CONCLUSIONS: Quality parameters of canine platelets under standard storage conditions were similar to those observed in human platelets. Our results have potential to be used for the routine evaluation and quality control in veterinary blood banks.

Report from the GHPP-BloodTrain inspection workshop in Harare the 20th to the 24th of May 2019.

During the training workshop on Inspection of Blood Establishments, which was hosted by the PEI GHPP BloodTrain in Harare from the 20th to the 24th of May 2019, participants from the National Regulatory Authorities from seven Sub-Sahara African countries presented their current experiences related to regulation and inspection of blood establishments in their respective countries. While in all seven countries regulation and inspection of conventional medicinal products manufacturer is performed, the regulatory situation of blood and blood components as well as inspection of blood establishments is still heterogeneous.

Banking with precision: transfusion medicine as a potential universal application in clinical genomics.

PURPOSE OF REVIEW: To summarize the most recent scientific progress in transfusion medicine genomics and discuss its role within the broad genomic precision medicine model, with a focus on the unique computational and bioinformatic aspects of this emergent field. RECENT FINDINGS: Recent publications continue to validate the feasibility of using next-generation sequencing (NGS) for blood group prediction with three distinct approaches: exome sequencing, whole genome sequencing, and PCR-based targeted NGS methods. The reported correlation of NGS with serologic and alternative genotyping methods ranges from 92 to 99%. NGS has demonstrated improved detection of weak antigens, structural changes, copy number variations, novel genomic variants, and microchimerism. Addition of a transfusion medicine interpretation to any clinically sequenced genome is proposed as a strategy to enhance the cost-effectiveness of precision genomic medicine. Interpretation of NGS in the blood group antigen context requires not only advanced immunohematology knowledge, but also specialized software and hardware resources, and a bioinformatics-trained workforce. SUMMARY: Blood transfusions are a common inpatient procedure, making blood group genomics a promising facet of precision medicine research. Further efforts are needed to embrace transfusion bioinformatic challenges and evaluate its clinical utility.

Twenty-five years later: has ISBT 128 fulfilled its promise?

Traceability is essential to any quality program for medical products of human origin (MPHO). Standardized terminology, coding, and labeling systems that include key elements for traceability support electronically readable information on product labels and improve the accuracy and efficiency of data collection. ISBT 128 is such a system. The first specification for ISBT 128 was published 25 years ago, and since that time it has become the global standard for labeling and information transfer for MPHO. Additionally, standardization of granular product description codes has supported hemovigilance and other activities that depend on aggregated data. This review looks back over the development, current status, and potential future applications of the ISBT 128 Standard.

How do I get an emergency civilian walking blood bank running?

The shift toward using a transfusion strategy in a ratio to mimic whole blood (WB) functionality has revitalized WB as a viable option to replace severe blood loss in civilian health care. A military-civilian collaboration has contributed to the reintroduction of WB at Haukeland University Hospital in Bergen, Norway. WB has logistical and hemostatic advantages in both the pre- and in-hospital settings where the goal is a perfectly timed balanced transfusion strategy. In this paper, we describe an event leading to activation of our emergency WB collection strategy for the first time. We evaluate the feasibility of our civilian walking blood bank (WBB) to cover the need of a massive amount of blood in an emergency situation. The challenges are discussed in relation to the different stages of the event with the recommendations for improvement in practice. We conclude that the use of pre-screened donors as a WBB in a civilian setting is feasible. The WBB can provide platelet containing blood components for balanced blood resuscitation in a clinically relevant time frame.