Patient blood management and blood conservation - Complimentary concepts and solutions for blood establishments and clinical services in South Africa and beyond.

Blood transfusions come with risks and high costs, and should be utilized only when clinically indicated. Decisions to transfuse are however not always well informed, and lack of clinician knowledge and education on good clinical transfusion practices contribute to the inappropriate use of blood. Low and middle-income countries in particular take much strain in their efforts to address blood safety challenges, demand-supply imbalances, high blood costs as well as high disease burdens, all of which impact blood usage and blood collections. Patient blood management (PBM), which is a patient-focused approach aimed at improving patient outcomes by preemptively diagnosing and correcting anaemia and limiting blood loss by cell salvage, coagulation optimization and other measures, has become a major approach to addressing many of the challenges mentioned. The associated decrease in the use of blood and blood products may be perceived as being in competition with blood conservation measures, which is the more traditional, but primarily product-focused approach. In this article, we hope to convey the message that PBM and blood conservation should not be seen as competing concepts, but rather complimentary strategies with the common goal of improving patient care. This offers opportunity to improve the culture of transfusion practices with relief to blood establishments and clinical services, not only in South Africa and LMICs, but everywhere. With the COVID-19 pandemic impacting blood supplies worldwide, this is an ideal time to call for educational interventions and awareness as an active strategy to improve transfusion practices, immediately and beyond.

Non-transplantable cord blood units as a source for adoptive immunotherapy of leukaemia and a paradigm of circular economy in medicine.

Advances in immunotherapy with T cells armed with chimeric antigen receptors (CAR-Ts), opened up new horizons for the treatment of B-cell lymphoid malignancies. However, the lack of appropriate targetable antigens on the malignant myeloid cell deprives patients with refractory acute myeloid leukaemia of effective CAR-T therapies. Although non-engineered T cells targeting multiple leukaemia-associated antigens [i.e. leukaemia-specific T cells (Leuk-STs)] represent an alternative approach, the prerequisite challenge to obtain high numbers of dendritic cells (DCs) for large-scale Leuk-ST generation, limits their clinical implementation. We explored the feasibility of generating bivalent-Leuk-STs directed against Wilms tumour 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) from umbilical cord blood units (UCBUs) disqualified for allogeneic haematopoietic stem cell transplantation. By repurposing non-transplantable UCBUs and optimising culture conditions, we consistently produced at clinical scale, both cluster of differentiation (CD)34+ cell-derived myeloid DCs and subsequently polyclonal bivalent-Leuk-STs. Those bivalent-Leuk-STs contained CD8+ and CD4+ T cell subsets predominantly of effector memory phenotype and presented high specificity and cytotoxicity against both WT1 and PRAME. In the present study, we provide a paradigm of circular economy by repurposing unusable UCBUs and a platform for future banking of Leuk-STs, as a 'third-party', 'off-the-shelf' T-cell product for the treatment of acute leukaemias.

Preparedness and activities of the anti-SARS-CoV-2 convalescent plasma bank in the Veneto region (Italy): An organizational model for future emergencies.

BACKGROUND: Convalescent plasma (CP) has been used in the past in various pandemics, in particular in H1N1, SARS and MERS infections. In Spring 2020, when ongoing the SARS-CoV-2 pandemics, the Veneto Region (V-R) has proposed setting-up an anti-SARS-CoV-2 CP (CCP) Bank, with the aim of preparing a supply of CCP immediately available in case of subsequest epidemic waves. MATERIALS AND METHODS: Key-points to be developed for a quick set-up of the V-R CCP Bank have been recruitment of donors recovered from COVID-19 infection, laboratory analysis for the biological qualification of the CCP units, including titre of neutralizing antibodies and reduction of pathogens, according to National Blood Centre (CNS) Directives, adaptation of the V-R Information Technology systems and cost analysis. Some activities, including diagnostic and viral inactivation processes, have been centralized in 2 or 3 sites. Laboratory analysis upon preliminary admission of the donor included all tests required by the Italian laws and the CNS directives. RESULTS: From April to August 2020, 3,298 people have contacted the V-R Blood Transfusion Services: of these, 1,632 have been evaluated and examined as first time donors and those found to be suitable have carried out 955 donations, from which 2,626 therapeutic fractions have been obtained, at a cost around 215,00 Euro. Since October 2020, the number of COVID-19 inpatients has had a surge with a heavy hospital overload. Moreover, the high request of CCP therapy by clinicians has been just as unexpected, showing a wide therapeutic use. CONCLUSIONS: The organizational model here presented, which has allowed the rapid collection of a large amount of CCP, could be useful when facing new pandemic outbreaks, especially in low and middle income countries, with generally acceptable costs.

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.

The Binns Program for Cord Blood Research: A novel model of cord blood banking for academic biomedical research.

Umbilical cord blood is an important graft source in the treatment of many genetic, hematologic, and immunologic disorders by hematopoietic stem cell transplantation. Millions of cord blood units have been collected and stored for clinical use since the inception of cord blood banking in 1989. However, the use of cord blood in biomedical research has been limited by access to viable samples. Here, we present a cost-effective, self-sustaining model for the procurement of fresh umbilical cord blood components for research purposes within hospital-affiliated academic institutions.

Liquid plasma reduces waste and health care expenses compared with thawed plasma at a Level I trauma center.

BACKGROUND: Balanced resuscitation strategies have led to increased utilization of plasma. Fresh frozen plasma that is thawed and never used is a large source of blood component wastage. Thawed plasma (TP) and can only be stored for 5 days. Liquid plasma (LP) has never been frozen and can be stored for 26 days. Due to longer storage duration, we hypothesized that using LP would result in decreased waste and cost savings compared with TP. METHODS: We performed a retrospective review of all trauma patients at our Level I trauma center in the years 2015 to 2016. We compared 2015 when only TP was used to 2016 when both TP and LP were used. All plasma units ordered for trauma patients were tracked until the time of transfusion or wastage. Wastage rates were compared between years and plasma type. RESULTS: There were 5,789 trauma patients admitted to our institution from 2015 to 2016. There were 4,107 plasma units ordered with 487 (11.9%) units wasted. During 2015, 2,021 total units of plasma were ordered with 273 (13.5%) units wasted which was a significantly higher rate than 2016 when 2,086 total units of plasma were ordered and 214 (10.3%) units were wasted (p = 0.0013). During 2016, 1,739 units of TP were ordered and 204 (11.7%) units were wasted which was significantly higher than LP wastage, 347 units ordered and 10 (2.9%) units wasted (p < 0.001). Of the 477 wasted TP units, 76.9% were ordered no more than two times before being wasted and 95.8% were ordered no more than three times before being wasted. Of the 10 LP units wasted, 40% were ordered no more than two times before being wasted, and 50% were ordered no more than three times before being wasted. If TP was wasted at the same rate as LP, 368 fewer units of plasma would have been wasted representing US $39,376 (US $107/unit) of wasted health care expenses. CONCLUSION: At a Level I trauma center, the addition of LP to the blood bank for trauma resuscitations significantly reduced plasma wastage rates and health care expenses. LEVEL OF EVIDENCE: Level III, Economic/Decision.

Provision of COVID-19 Convalescent Plasma in a Resource-Constrained State.

BACKGROUND: Arkansas is a rural state of 3 million people. It is ranked fifth for poverty nationally. The first case of coronavirus disease 2019 (COVID-19) in Arkansas occurred on 11 March 2020. Since then, approximately 8% of all Arkansans have tested positive. Given the resource limitations of Arkansas, COVID-19 convalescent plasma (CCP) was explored as a potentially lifesaving, therapeutic option. Therefore, the Arkansas Initiative for Convalescent Plasma was developed to ensure that every Arkansan has access to this therapy. STUDY DESIGN AND METHOD: This brief report describes the statewide collaborative response from hospitals, blood collectors, and the Arkansas Department of Health (ADH) to ensure that CCP was available in a resource-limited state. RESULTS: Early contact tracing by ADH identified individuals who had come into contact with "patient zero" in early March. Within the first week, 32 patients tested positive for COVID-19. The first set of CCP collections occurred on 9 April 2020. Donors had to be triaged carefully in the initial period, as many had recently resolved their symptoms. From our first collections, with appropriate resource and inventory management, we collected sufficient CCP to provide the requested number of units for every patient treated with CCP in Arkansas. CONCLUSIONS: The Arkansas Initiative, a statewide effort to ensure CCP for every patient in a resource-limited state, required careful coordination among key players. Collaboration and resource management was crucial to meet the demand of CCP products and potentially save lives.

Stochastic Inventory Model for Minimizing Blood Shortage and Outdating in a Blood Supply Chain under Supply and Demand Uncertainty.

Purpose: Blood, like fresh produce, is a perishable element, with platelets having a limited lifetime of five days and red blood cells lasting 42 days. To manage the blood supply chain more effectively under demand and supply uncertainty, it is of considerable importance to developing a practical blood supply chain model. This paper proposed an essential blood supply chain model under demand and supply uncertainty. Methods: This study focused on how to manage the blood supply chain under demand and supply uncertainty effectively. A stochastic mixed-integer linear programming (MILP) model for the blood supply chain is proposed. Furthermore, this study conducted a sensitivity analysis to examine the impacts of the coefficient of demand and supply variation and the cost parameters on the average total cost and the performance measures (units of shortage, outdated units, inventory holding units, and purchased units) for both the blood center and hospitals. Results: Based on the results, the hospitals and the blood center can choose the optimal ordering policy that works best for them. From the results, we observed that when the coefficient of demand and supply variation is increased, the expected supply chain cost increased with more outdating units, shortages units, and holding units due to the impacts of supply and demand fluctuation. Variation in the inventory holding and expiration costs has an insignificant effect on the total cost. Conclusions: The model developed in this paper can assist managers and pathologists at the blood donation centers and hospitals to determine the most efficient inventory policy with a minimum cost based on the uncertainty of blood supply and demand. The model also performs as a decision support system to help health care professionals manage and control blood inventory more effectively under blood supply and demand uncertainty, thus reducing shortage of blood and expired wastage of blood.

Designing an optimal inventory management model for the blood supply chain: Synthesis of reusable simulation and neural network.

Blood supply managers in the blood supply chain have always sought to create enough reserves to increase access to different blood products and reduce the mortality rate resulting from expired blood. Managers' adequate and timely response to their customers is considered vital due to blood perishability, uncertainty of blood demand, and the direct relationship between the availability/lack of blood supply and human life. Further to this, hospitals' awareness of the optimal amount of requests from suppliers is vital to reducing blood return and blood loss, since the loss of blood products surely leads to high expenses. This paper aims to design an optimal management model of blood transfusion network by a synthesis of reusable simulation technique (applicable to all bases) and deep neural network (the latest neural network technique) with multiple recursive layers in the blood supply chain so that the costs of blood waste, return, and shortage can be reduced. The model was implemented on and developed for the blood transfusion network of Khorasan Razavi, which has 6 main bases active from October 2015 to October 2017. In order to validate the data, the data results of the variables examined with the real data were compared with those of the simulation, and the insignificant difference between them was investigated by t test. The solution of the model facilitated a better prediction of the amount of hospital demand, the optimal amount of safety reserves in the bases, the optimal number of hospital orders, and the optimal amount of hospital delivery. This prediction helps significantly reduce the return of blood units to bases, increase availability of inventories, and reduce costs.

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.

Supplemental findings of the 2017 National Blood Collection and Utilization Survey.

INTRODUCTION: This report provides supplemental results from the 2017 National Blood Collection and Utilization Survey on characteristics of the donor population, autologous and directed donations and transfusions, platelets, plasma and granulocyte transfusions, pediatric transfusions, severe donor-related adverse events, cost of blood units, hospitals policies and practices, and inventory, dosing, and supply. METHODS: Weighting and imputation were used to generate national estimates including number of donors, donations, donor deferrals, autologous and directed donations and transfusions, severe donor-related adverse events, platelet and plasma collections and transfusions, number of cross-match procedures, irradiation and leukoreduction, and pediatric transfusions. RESULTS: Between 2015 and 2017, successful donations decreased slightly by 2.1% with a 10.3% decrease in donations by persons aged 16-18 years and a 14.4% increase in donations by donors aged >65 years. The median price paid for blood components by hospitals decreased from $211 to $207 for leukoreduced red blood cell units, from $523 to $517 for leukoreduced apheresis platelet units, and from $54 to $51 for fresh frozen plasma units. Plasma transfusions decreased 13.6%, but group AB plasma units transfused increased 24.7%. CONCLUSION: Between 2015 and 2017, blood donations declined slightly because of decreases in donations from younger donors, but the number of donations from older donors increased. The price hospitals pay for blood has continued to decrease. Plasma transfusions have decreased, but the proportion of plasma transfusions involving group AB plasma have increased.

A novel protocol to maintain continuous access to thawed plasma at a rural trauma center.

BACKGROUND: Early administration of plasma improves mortality in massively transfused patients, but the thawing process causes delay. Small rural centers have been reluctant to maintain thawed plasma due to waste concerns. Our 254-bed rural Level II trauma center initiated a protocol allowing continuous access to thawed plasma, and we hypothesized its implementation would not increase waste or cost. METHODS: Two units of thawed plasma are continuously maintained in the trauma bay blood refrigerator. After 3 days, these units are replaced with freshly thawed plasma and returned to the blood bank for utilization prior to their 5-day expiration date. The blood bank monitors and rotates the plasma. Only trauma surgeons can use the plasma stored in the trauma bay. Wasted units and cost were measured over a 12-month period and compared with the previous 2 years. RESULTS: The blood bank thawed 1127 units of plasma during the study period assigning 274 to the trauma bay. When compared with previous years, we found a significant increase in waste (p < 0.001) and cost (p = 0.020) after implementing our protocol. It cost approximately US $125/month extra to maintain continuous access to thawed plasma during the study period. DISCUSSION: A protocol to maintain thawed plasma in the trauma bay at a rural Level II trauma center resulted in a miniscule increase in waste and cost when considering the scope of maintaining a trauma center. We think this cost is also minimal when compared with the value of having immediate access to thawed plasma. Constant availability of thawed plasma can be offered at smaller rural centers without a meaningful impact on cost. LEVEL OF EVIDENCE: Economic and Value-based Evaluations, Level III.

Benefits of VISION Max automated cross-matching in comparison with manual cross-matching: A multidimensional analysis.

BACKGROUND: VISION Max (Ortho-Clinical Diagnostics, Raritan, NJ, USA) is a newly introduced automated blood bank system. Cross-matching (XM) is an important test confirming safety by simulating reaction between packed Red Blood Cells (RBCs) and patient blood in vitro before transfusion. We assessed the benefits of VISION Max automated XM (A-XM) in comparison with those of manual XM (M-XM) by using multidimensional analysis (cost-effectiveness and quality improvement). MATERIALS AND METHODS: In a total of 327 tests (130 patients), results from A-XM and M-XM were compared. We assessed the concordance rate, risk priority number (RPN), turnaround time, hands-on time, and the costs of both methods. We further simulated their annual effects based on 37,937 XM tests in 2018. RESULTS: The concordance rate between A-XM and M-XM was 97.9% (320/327, kappa = 0.83), and the seven discordant results were incompatible for transfusion in A-XM, while compatible for transfusion in M-XM. None of the results was incompatible for transfusion in A-XM, while compatible for transfusion in M-XM, meaning A-XM detect agglutination more sensitively and consequently provides a more safe result than M-XM. A-XM was estimated to have a 6.3-fold lower risk (229 vs. 1,435 RPN), shorter turnaround time (19.1 vs. 23.3 min, P < 0.0001), shorter hands-on time (1.1 vs. 5.3 min, P < 0.0001), and lower costs per single test than M-XM (1.44 vs. 2.70 USD). A-XM permitted annual savings of 46 million RPN, 15.1 months of daytime workers' labor, and 47,042 USD compared with M-XM. CONCLUSION: This is the first attempt to implement A-XM using VISION Max. VISION Max A-XM appears to be a safe, practical, and reliable alternative for pre-transfusion workflow with the potential to improve quality and cost-effectiveness in the blood bank.

Blood product wastage reduction by utilising low-cost, low-impact multimodal physician-to-physician communication initiatives.

OBJECTIVES: To assess a multimodal physician-to-physician communication initiative that is low in cost and impact to daily workflow to reduce blood product wastage. BACKGROUND: Blood product stewardship is an important issue in all hospital systems. Previous studies have proposed low-cost interventions to reduce blood product wastage, but few have evaluated improvements in communication between the blood bank and providers. We undertook a prospective quality improvement project focusing on improving communication to reduce blood product wastage. METHODS: We conducted a prospective quality improvement project over the first quarter of 2017, identifying patients with issued but unused blood products. Each service overseeing the care of patients identified on the unit status report was contacted through two possible methods: (i) phone or (ii) proprietary Health Insurance Portability and Accountability Act of 1996 compliant digital messaging application. Collected variables included reserved blood product type and participant time spent. Outcomes included the rate of blood product release and changes in wastage compared with historical data tracked by the blood bank. RESULTS: Eight hundred and forty products were reserved during the study period, of which 436 (52%) were released. Average participant times ranged from 2 ± 1 min to 15 ± 4 min with no significant differences in time spent between participants (P = 0·194). Compared with the average product wastage 10 months prior to project initiation, there were significant reductions in the average wastage for platelets (5·3 ± 2·5 units vs 2·5 ± 1·5 units, P = 0·05), RBCs (6·1 ± 3·7 units vs 0 ± 0 units, P = 0·01) and overall wastage (58·3 ± 14·9 units vs 40 ± 15·7 units, P = 0·05). CONCLUSION: Efforts focusing on improving provider-to-provider communication can reduce blood product wastage.

The global need and availability of blood products: a modelling study.

BACKGROUND: Blood transfusions are an important resource of every health-care system, with often limited supply in low-income and middle-income countries; however, the degree of unmet need for blood transfusions is often unknown. We therefore aimed to estimate the blood transfusion need and supply at national level to determine gaps in transfusion services globally. METHODS: We did a modelling study involving 195 countries and territories. We used blood component preparation data from 2011-13 to estimate blood availability for 180 (92%) of 195 countries from the WHO Global Status Report on Blood Safety and Availability. We calculated disease-specific transfusion needs per prevalent case for 20 causes in the USA using the National (Nationwide) Inpatient Sample dataset between the years 2000 and 2014, and the State Inpatient Databases between 2003 and 2007 from the Healthcare Cost and Utilization Project. Using prevalence estimates for the USA from the Global Burden of Disease (GBD) 2017 study, we estimated the ideal disease specific-transfusion rate as the lowest rate from the years 2000 to 2014. We applied this rate to GBD prevalence results for 195 countries to estimate transfusion needs. Unmet need was the difference between the estimated supply and need. FINDINGS: In 2017, the global blood need was 304 711 244 (95% uncertainty interval [UI] 293 064 637-314 049 479) and the global blood supply was 272 270 243 (268 002 639-276 698 494) blood product units, with a need-to-supply ratio of 1·12 (95% UI 1·07-1·16). Of the 195 countries, 119 (61%) did not have sufficient blood supply to meet their need. Across these 119 countries, the unmet need totalled 102 359 632 (95% UI 93 381 710-111 360 725) blood product units, equal to 1849 (1687-2011) units per 100 000 population globally. Every country in central, eastern, and western sub-Saharan Africa, Oceania, and south Asia had insufficient blood to meet their needs. INTERPRETATION: Our data suggest that the gap between need and supply is large in many low-income and middle-income countries, and reinforce that the WHO target of 10-20 donations per 1000 population is an underestimate for many countries. A continuous expansion and optimisation of national transfusion services and implementation of evidence-based strategies for blood availability is needed globally, as is more government support, financially, structurally, and through establishment of a regulatory oversight to ensure supply, quality, and safety in low-income and middle-income countries. FUNDING: National Institutes of Health.

The direct labor cost for providing life-saving blood to air medical transport for pre-hospital transfusion.

An IRB approved 2-year review and cost analysis of all packed red blood cells (pRBCs) issued, transfused and returned to the blood bank by air medical transport services for pre-hospital transfusion was performed. The cost to the blood bank for issuing and returning pRBCs that were not transfused in the pre-hospital setting was $3.24 per unit. Over the study period, there were 334 pRBCs not transfused by air medical services and returned to the blood bank totaling $1082.16 in direct labor costs, a trivial amount for providing possibly life-saving blood for pre-hospital transfusion.

Blood donations mode: Assessment of the Lebanese model.

Voluntary non-remunerated donations remain the cornerstone for a safe and sustainable blood supply. According to the World Health Organization and other international scientific committees, all nations must switch their system of blood collection to voluntary non-remunerated donation. Several other types of blood donations still exist nowadays that will be discussed. Lebanon, similarly to other developing countries, is struggling to achieve 100% voluntary non-remunerated donations for the many existing social, demographic, cultural and economic problems. Replacement donations remain the predominant type, which creates huge burden on both hospital blood banks and patient families. Despite the limited resources, some improvements have been made recently in this field and Lebanon seems to be on the road of achieving 100% voluntary non-remunerated blood donation as requested by the World Health Organization. The Lebanese experience is worth sharing so that neighbouring countries facing similar problems could benefit from it.