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.

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.

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.

What will Become of the Taxpayer Investment in Public Cord Blood Stem Cell Banking?

Cord Blood (CB) is a unique and readily available source of hematopoietic stem cells for transplantation. CB also contains other types of stem cells, including endothelial stem cells and mesenchymal stem cells, that may prove useful in non-traditional clinical uses. Genetic and molecular analyses have demonstrated that CB stem cells lie somewhere between mature stem cells like those found in Bone Marrow (BM), and fetal stem cells. After 25 years of clinical experience, CB is now used in the same fashion as BM for all typical malignant and genetic diseases treated by bone marrow transplant. Due to the establishment of CB banks in the US and abroad, more than 35,000 CB transplants have been performed over the past 25 years. An average of 700-800 CB transplants are performed annually. In addition, CB is now used more frequently for regenerative medicine and tissue engineering applications. At first glance, it seems that everything could not be better with the public cord blood banks and the use of their samples in the clinic. However, a recent report by the Rand Corp. reviewed the US national cord blood stem cell banking program and detailed many ongoing problems. However, some details were omitted from the report that would shed some light on the causes of many of the problems. This paper will summarize the status of the public cord blood stem cell banking program in the US, detail the problems associated with the program that could jeopardize its existence and suggest possible solutions to resolve these issues.

Impact of Prothrombin Complex Concentrate on Blood Use, Cost, and Outcomes in Heart Transplantation.

BACKGROUND: Left ventricular assist device (LVAD) recipients undergoing heart transplantation have increased bleeding risk. We compared conventional warfarin reversal with fresh frozen plasma vs 4-factor prothrombin complex concentrate (PCC) and the effect on transfusion requirements, blood bank costs, and clinical outcomes. METHODS: A retrospective review identified 60 consecutive LVAD recipients undergoing heart transplantation divided into two groups: 30 (no PCC) received fresh frozen plasma and 30 (PCC) received PCC. Patient characteristics, intraoperative and postoperative transfusion requirements, short-term clinical outcomes, and blood bank costs were compared. PCC association with transfusion requirements was assessed by multivariate linear regression. RESULTS: Patients who received PCC were younger (50 ± 11 vs 57 ± 13 years, p = 0.02), fewer had ischemic cardiomyopathy (23% vs 60%, p = 0.01), had more than one prior sternotomy (7% vs 30%, p = 0.04), and had higher preoperative hemoglobin (11.8 ± 1.8 vs 10.4 ± 1.8 g/dL, p = 0.01). The PCC group had a significantly shorter bypass time (185 vs 217 minutes, p = 0.01), received less fresh frozen plasma (2 vs 5 units, p = 0.03), cryoprecipitate (0 vs 2 units, p = 0.05), and total blood products (9 vs 13.5 units, p = 0.03) intraoperatively, and was less likely to require delayed sternal closure (3% vs 23%, p = 0.05). On multivariate linear regression, PCC was significantly associated with decreased intraoperative transfusion (ß = -6.09, p = 0.02). There was no difference in thromboembolic events or in-hospital death. Total blood bank costs were $4,949 for PCC and $3,677 for no PCC (p = 0.01). CONCLUSIONS: Although more costly, PCC reduced transfusion requirements and delayed sternal closure in heart transplant recipients bridged with LVAD, justifying its use over traditional warfarin reversal.

Accurate costs of blood transfusion: a microcosting of administering blood products in the United Kingdom National Health Service.

BACKGROUND: In an environment of limited health care resources, it is crucial for health care systems which provide blood transfusion to have accurate and comprehensive information on the costs of transfusion, incorporating not only the costs of blood products, but also their administration. Unfortunately, in many countries accurate costs for administering blood are not available. Our study aimed to generate comprehensive estimates of the costs of administering transfusions for the UK National Health Service. STUDY DESIGN AND METHODS: A detailed microcosting study was used to cost two key inputs into transfusion: transfusion laboratory and nursing inputs. For each input, data collection forms were developed to capture staff time, equipment, and consumables associated with each step in the transfusion process. Costing results were combined with costs of blood product wastage to calculate the cost per unit transfused, separately for different blood products. Data were collected in 2014/15 British pounds and converted to US dollars. RESULTS: A total of 438 data collection forms were completed by 74 staff. The cost of administering blood was $71 (£49) per unit for red blood cells, $84 (£58) for platelets, $55 (£38) for fresh-frozen plasma, and $72 (£49) for cryoprecipitate. CONCLUSIONS: Blood administration costs add substantially to the costs of the blood products themselves. These are frequently incurred costs; applying estimates to the blood components supplied to UK hospitals in 2015, the annual cost of blood administration, excluding blood products, exceeds $175 (£120) million. These results provide more accurate estimates of the total costs of transfusion than those previously available.

Cord Blood Banking for Potential Future Transplantation.

This policy statement is intended to provide information to guide pediatricians, obstetricians, and other medical specialists and health care providers in responding to parents' questions about cord blood donation and banking as well as the types (public versus private) and quality of cord blood banks. Cord blood is an excellent source of stem cells for hematopoietic stem cell transplantation in children with some fatal diseases. Cord blood transplantation offers another method of definitive therapy for infants, children, and adults with certain hematologic malignancies, hemoglobinopathies, severe forms of T-lymphocyte and other immunodeficiencies, and metabolic diseases. The development of universal screening for severe immunodeficiency assay in a growing number of states is likely to increase the number of cord blood transplants. Both public and private cord blood banks worldwide hold hundreds of thousands of cord blood units designated for the treatment of fatal or debilitating illnesses. The procurement, characterization, and cryopreservation of cord blood is free for families who choose public banking. However, the family cost for private banking is significant and not covered by insurance, and the unit may never be used. Quality-assessment reviews by several national and international accrediting bodies show private cord blood banks to be underused for treatment, less regulated for quality control, and more expensive for the family than public cord blood banks. There is an unquestionable need to study the use of cord blood banking to make new and important alternative means of reconstituting the hematopoietic blood system in patients with malignancies and blood disorders and possibly regenerating tissue systems in the future. Recommendations regarding appropriate ethical and operational standards (including informed consent policies, financial disclosures, and conflict-of-interest policies) are provided for physicians, institutions, and organizations that operate or have a relationship with cord blood banking programs. The information on all aspects of cord blood banking gathered in this policy statement will facilitate parental choice for public or private cord blood banking.

The cost-effectiveness of predonation screening for transfusion transmissible infections using rapid test kits in a hospital-based blood transfusion centre.

OBJECTIVE: Blood transfusion practice emphasises safety, efficacy and appropriate use. These require cost-effective programme management. This study focused on the cost of screening for transfusion transmissible infections (TTI). METHODS: This was a 1 year (2016) analysis of screening in a hospital-based transfusion centre. The cost of screening all blood donors by ELISA was compared to the cost of serial screening starting from rapid kit, taking into account, the estimated cost of blood bags prevented from discard after ELISA screening (attributable cost). The cost of voluntary donor drive plus cost of ELISA screening was compared with the present cost of screening. RESULTS: A total of 5591 donors were screened for HIV, hepatitis B and C using the rapid kit, 291 donors were deferred (5.2%). A total of 5300 units were further screened by ELISA. A total of 435 blood units (8.2%) were discarded due to TTI positivity. TTI positivity rate was 12.98%. Only 2.36% were voluntary donors and among these 9.1% were TTI positive. The attributable cost of serial screening was 55,653.5 USD while that of screening by ELISA only was 55,910 USD. The attributable cost of rapid screening for only hepatitis B and then ELISA was 53,313.9 USD taking into consideration that 187 blood units would be prevented from undue discard. CONCLUSIONS: This analysis demonstrated that with proper donor selection, rapid screening for hepatitis B virus only before ELISA screening is more cost-effective. This will also reduce the waiting time for donors and counselling if HIV positive.

Developing Induced Pluripotent Stem Cell-Based Therapy for the Masses.

The discovery of induced pluripotent stem cells and the ability to manufacture them using clinically compliant protocols has the potential to revolutionize the field of regenerative medicine. However, realizing this potential requires the development of processes that are reliable, reproducible, and cost-effective and that at the same time do not compromise the safety of the individuals receiving this therapy. In the present report, we discuss how cost reductions can be obtained using our experience with obtaining approval of biologic agents, autologous therapy, and the recent approval of cord blood banks. Significance: For therapy to be widely available, the cost of manufacturing stem cells must be reduced. The steps proposed in the present report, when implemented, have the potential to reduce these costs significantly.

Banking or Bankrupting: Strategies for Sustaining the Economic Future of Public Cord Blood Banks.

BACKGROUND: Cord blood is an important source of stem cells. However, nearly 90% of public cord blood banks have declared that they are struggling to maintain their financial sustainability and avoid bankruptcy. The objective of this study is to evaluate how characteristics of cord blood units influence their utilization, then use this information to model the economic viability and therapeutic value of different banking strategies. METHODS: Retrospective analysis of cord blood data registered between January 1st, 2009 and December 31st, 2011 in Bone Marrow Donor Worldwide. Data were collected from four public banks in France, Germany and the USA. Samples were eligible for inclusion in the analysis if data on cord blood and maternal HLA typing and biological characteristics after processing were available (total nucleated and CD34+ cell counts). 9,396 banked cord blood units were analyzed, of which 5,815 were Caucasian in origin. A multivariate logistic regression model assessed the influence of three parameters on the CBU utilization rate: ethnic background, total nucleated and CD34+ cell counts. From this model, we elaborated a Utilization Score reflecting the probability of transplantation for each cord blood unit. We stratified three Utilization Score thresholds representing four different banking strategies, from the least selective (scenario A) to the most selective (scenario D). We measured the cost-effectiveness ratio for each strategy by comparing performance in terms of number of transplanted cord blood units and level of financial deficit. RESULTS: When comparing inputs and outputs over three years, Scenario A represented the most extreme case as it delivered the highest therapeutic value for patients (284 CBUs transplanted) along with the highest financial deficit (USD 5.89 million). We found that scenario C resulted in 219 CBUs transplanted with a limited deficit (USD 0.98 million) that charities and public health could realistically finance over the long term. We also found that using a pre-freezing level of 18 x 10(8) TNC would be the most cost-effective strategy for a public bank. CONCLUSION: Our study shows that a swift transition from strategy A to C can play a vital role in preventing public cord blood banks worldwide from collapsing.

[Treatment of anemia in Patient Blood Management from an economic perspective]. / Tratamiento de la anemia en el "Patient Blood Management" desde una perspectiva económica.

The liberal use of transfusions is not only a risk for patients but also represents a significant healthcare expenditure. The rational use of allogeneic blood transfusions and the use of transfusion alternatives, such as the optimization of preoperative hemoglobin levels, can offer substantial savings to health departments by reducing the cost of transfusions and the morbidity related to the transfusions.

The role and potential of umbilical cord blood in an era of new therapies: a review.

In light of pioneering findings in the 1980s and an estimation of more than 130 million global annual births, umbilical cord blood (UCB) is considered to be the most plentiful reservoir of cells and to have regenerative potential for many clinical applications. Although UCB is used mainly against blood disorders, the spectrum of diseases for which it provides effective therapy has been expanded to include non-hematopoietic conditions; UCB has also been used as source for regenerative cell therapy and immune modulation. Thus, collection and banking of UCB-derived cells have become a popular option. However, there are questions regarding the cost versus the benefits of UCB banking, and it also raises complex ethical and legal issues. This review discusses many issues surrounding the conservation of UCB-derived cells and the great potential and current clinical applications of UCB in an era of new therapies. In particular, we describe the practical issues inherent in UCB collection, processing, and long-term storage as well as the different types of 'stem' or progenitor cells circulating in UCB and their uses in multiple clinical settings. Given these considerations, the trend toward UCB will continue to provide growing assistance to health care worldwide.

Cord Blood Banking in the Arab World: Current Status and Future Developments.

Umbilical cord blood transplants are now used to treat numerous types of immune- and blood-related disorders and genetic diseases. Cord blood (CB) banks play an important role in these transplants by processing and storing CB units. In addition to their therapeutic potential, these banks raise ethical and regulatory questions, especially in emerging markets in the Arab world. In this article, the authors review CB banking in five countries in the region, Jordan, Saudi Arabia, Egypt, Qatar, and the United Arab Emirates, selected for their different CB banking policies and initiatives. In assessing these case studies, the authors present regional trends and issues, including religious perspectives, policies, and demographic risk factors. This research suggests strong incentives for increasing the number of CB units that are collected from and available to Arab populations. In addition, the deficit in knowledge concerning public opinion and awareness in the region should be addressed to ensure educated decision-making.

Are hybrid umbilical cord blood banks really the best of both worlds?

Since the first use of umbilical cord blood (UCB) as a medical therapy, the number of UCB banks worldwide has grown. Public UCB banks offer the option of altruistic donation, whereas private banks allow a product to be stored for the exclusive use of the paying client. With many more UCB products banked privately than publicly in countries such as the USA, hybrid models blending aspects of public and private banking have been proposed. One such bank is in operation in the UK. In this paper we review the hybrid UCB model and conclude that it offers limited benefit to the general public. Furthermore, compared with private banking, this model provides few advantages and potential disadvantages to private clients.