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Alana Delaforce,1– 3 Jed Duff,1,4 Judy Munday,3– 5 Shannon Farmer,6,7 Kristin Miller,2 Lynne Glover,2 Christopher Corney,2 Cameron Hurst,8 Gareth Ansell,2,9 Naadir Gutta,2,9 Haitham Tuffaha,10 Janet Hardy2,3 1School of Nursing and Midwifery, The University of Newcastle, Callaghan, NSW, Australia; 2Mater Health Services, South Brisbane, QLD, Australia; 3Mater Research Institute-UQ, South Brisbane, QLD, Australia; 4Centre for Healthcare Transformation/School of Nursing, Queensland University of Technology, Kelvin Grove, QLD, Australia; 5Faculty of Health and Sport Science, The University of Agder, Kristiansand, Norway; 6Department of Haematology, Royal Perth Hospital, Perth, Western Australia, Australia; 7Medical School and Division of Surgery, The University of Western Australia, Perth, Western Australia, Australia; 8QIMR Berghoffer Medical Research Institute, Brisbane, QLD, Australia; 9School of Clinical Medicine - Mater Clinical Unit, The University of Queensland, St Lucia, QLD, Australia; 10Centre for the Business and Economics of Health, The University of Queensland, St Lucia, QLD, AustraliaCorrespondence: Alana Delaforce Level 6, Duncombe Building, Mater Hospital Brisbane, South Brisbane, QLD, 4101, AustraliaTel +61 7 3163 2853Email alana.delaforce@mater.org.auIntroduction: Blood transfusions are a risk factor for increased morbidity, mortality, and length of hospital stay. Patient blood management guidelines provide guidance to reduce risk and improve patient outcomes. They outline steps to help prevent transfusions and considerations for when deciding to transfuse. One recommendation to prevent unnecessary transfusion is to optimize patients using Pre-operative Anemia and Iron Deficiency Screening, Evaluation and Management Pathways (PAIDSEM-P). The uptake of these recommendations is highly variable, and an effective approach to implementing them in a tailored and context-specific manner remains elusive.Method and Design: A mixed-methods, interventional study, using a type two-hybrid effectiveness-implementation design, will evaluate the impact of a change package to improve the uptake of PAIDSEM-P. The change package consists of the intervention (PAIDSEM-P) supported by theoretically informed implementation strategies. Pre- and post-implementation, retrospective health record reviews will determine the effect of the change package on provider outcomes, including compliance with guideline recommendations as measured by the proportion of patients who have the appropriate tests performed, and, if required, appropriate treatment and/or referrals. Patient outcomes will be measured by checking for any difference in the proportion of patients with anemia on the day of surgery and the proportion of patients who receive a blood transfusion during the peri-operative period. An economic evaluation will be conducted to compare health outcomes and costs. The feasibility, acceptability and appropriateness of the PAIDSEM-P will be assessed using a quantitative, validated survey to measure implementation outcomes.Discussion: Testing of implementation theory is required to advance understanding of what works, in what context, and the impact on implementation success. This study aims to evaluate the impact of a theoretically informed change package on improving the uptake of PAIDSEM-P. If successful, it will also provide a framework for health care facilities to follow when addressing other evidence-practice gaps.Keywords: patient blood management, implementation, anemia, iron deficiency, surgery

Previous research shows that competition can increase altruistic behaviour, however, the majority of such research focuses on financial costs and so our understanding is currently limited. Subsequently, the present study explored how competitive altruism can affect prosocial behaviour where time spent is the currency, using a real world charity. A sample of 67 men and 71 women completed the online altruistic task. As hypothesised, significant differences in giving behaviour due to competition were present in men but not women, suggesting that men use time spent here as a signal in mate choice scenarios. These findings therefore expand upon previous research on financial altruism, using artificial and/or hypothetical scenarios, by demonstrating that competitive altruism can be applied to real-world scenarios, where prosocial behaviours are of benefit. It also builds on previous research showing that men can compete with other men to display their altruistic nature to potential mates.

The saving of many lives in history has been duly credited to blood transfusions. What is frequently overlooked is the fact that, in light of a wealth of evidence as well as other management options, a therapy deemed suitable yesterday may no longer be the first choice today. Use of blood has not been based upon scientific evaluation of benefits, but mostly on anecdotal experience and a variety of factors are challenging current practice. Blood is a precious resource with an ever limiting supply due to the aging population. Costs have also continually increased due to advances (and complexities) in collection, testing, processing and administration of transfusion, which could make up 5% of the total health service budget. Risks of transfusions remain a major concern, with advances in blood screening and processing shifting the profile from infectious to non-infectious risks. Most worrying though, is the accumulating literature demonstrating a strong (often dose-dependent) association between transfusion and adverse outcomes. These include increased length of stay, postoperative infection, morbidity and mortality. To this end, a recent international consensus conference on transfusion outcomes (ICCTO) concluded that there was little evidence to corroborate that blood would improve patients' outcomes in the vast majority of clinical scenarios in which transfusions are currently routinely considered; more appropriate clinical management options should be adopted and transfusion avoided wherever possible. On the other hand, there are patients for whom the perceived benefits of transfusion are likely to outweigh the potential risks. Consensus guidelines for blood component therapy have been developed to assist clinicians in identifying these patients and most of these guidelines have long advocated more conservative 'triggers' for transfusion. However, significant variation in practice and inappropriate transfusions are still prevalent. The 'blood must always be good philosophy' continues to permeate clinical practice. An alternative approach, however, is being adopted in an increasing number of centres. Experience in managing Jehovah's Witness patients has shown that complex care without transfusion is possible and results are comparable with, if not better than those of transfused patients. These experiences and rising awareness of downsides of transfusion helped create what has become known as 'patient blood management'. Principles of this approach include optimizing erythropoiesis, reducing surgical blood loss and harnessing the patient's physiological tolerance of anaemia. Treatment is tailored to the individual patient, using a multidisciplinary team approach and employing a combination of modalities. Results have demonstrated reduction of transfusion, improved patient outcomes and patient satisfaction. Significant healthcare cost savings have also followed. Despite the success of patient blood management programmes and calls for practice change, the potential and actual harm to patients caused through inappropriate transfusion is still not sufficiently tangible for the public and many clinicians. This has to change. The medical, ethical, legal and economic evidence cannot be ignored. Patient blood management needs to be implemented as the standard of care for all patients.

BACKGROUND This study investigated the association between nadir anemia and mortality and length of stay (LOS) in a general population of hospitalized patients. STUDY DESIGN AND METHODS A retrospective cohort study of tertiary hospital admissions in Western Australia between July 2010 and June 2015. Outcome measures were in-hospital mortality and LOS. RESULTS Of 80,765 inpatients, 45,675 (56.55%) had anemia during admission. Mild and moderate/severe anemia were independently associated with increased in-hospital mortality (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.36-1.86, p = 0.001; OR 2.77, 95% CI 2.32-3.30, p < 0.001, respectively). Anemia was also associated with increased LOS, demonstrating a larger effect in emergency (mild anemia-incident rate ratio [IRR] 1.52, 95% CI 1.48-1.56, p < 0.001; moderate/severe anemia-IRR 2.18, 95% CI 2.11-2.26, p < 0.001) compared to elective admissions (mild anemia-IRR 1.30, 95% CI 1.21-1.41, p < 0.001; moderate/severe anemia-IRR 1.69, 95% CI 1.55-1.83, p < 0.001). LOS was longer in patients who developed anemia during admission compared to those who had anemia on admission (IRR 1.13, 95% CI 1.10-1.17, p < 0.001). Red cell transfusion was independently associated with 2.23 times higher odds of in-hospital mortality (95% CI 1.89-2.64, p < 0.001) and 1.31 times longer LOS (95% CI 1.25-1.37, p < 0.001). CONCLUSION More than one-third of patients not anemic on admission developed anemia during admission. Even mild anemia is independently associated with increased mortality and LOS; however, transfusion to treat anemia is an independent and additive risk factor.

Background Both anaemia and red blood cell (RBC) transfusion are common and associated with adverse outcomes in patients admitted to the intensive care unit (ICU). The aim of this study was to determine whether serum hepcidin concentration, measured early after ICU admission in patients with anaemia, could identify a group in whom intravenous (IV) iron therapy decreased the subsequent RBC transfusion requirement. Methods We conducted a prospective observational study nested within a multicenter randomized controlled trial (RCT) of IV iron versus placebo. The study was conducted in the ICUs of four tertiary hospitals in Perth, Western Australia. Critically ill patients with haemoglobin (Hb) of

BACKGROUND Little is published on patient blood management (PBM) programs in hematology. In 2008 Western Australia announced a health system–wide PBM program with PBM staff appointments commencing in November 2009. Our aim was to assess the impact this program had on blood utilization and patient outcomes in intensive chemotherapy for acute leukemia or hematopoietic stem cell transplantation. STUDY DESIGN AND METHODS A retrospective study of 695 admissions at two tertiary hospitals receiving intensive chemotherapy for acute leukemia or undergoing hematopoietic stem cell transplantation between July 2010 and December 2014 was conducted. Main outcomes included pre–red blood cell (RBC) transfusion hemoglobin (Hb) levels, single-unit RBC transfusions, number of RBC and platelet (PLT) units transfused per admission, subsequent day case transfusions, length of stay, serious bleeding, and in-hospital mortality. RESULTS Over the study period, the mean RBC units transfused per admission decreased 39% from 6.1 to 3.7 (p < 0.001), and the mean PLT units transfused decreased 35% from 6.3 to 4.1 (p < 0.001), with mean RBC and PLT units transfused for follow-up day cases decreasing from 0.6 to 0.4 units (p < 0.001). Mean pre-RBC transfusion Hb level decreased from 8.0 to 6.8 g/dL (p < 0.001), and single-unit RBC transfusions increased 39% to 67% (p < 0.001). This reduction represents blood product cost savings of AU$694,886 (US$654,007). There were no significant changes in unadjusted or adjusted length of stay, serious bleeding events, or in-hospital mortality over the study. CONCLUSION The health system–wide PBM program had a significant impact, reducing blood product use and costs without increased morbidity or mortality in patients receiving intensive chemotherapy for acute leukemia or hematopoietic stem cell transplantation.

BACKGROUND Patient blood management (PBM) programs are associated with improved patient outcomes, reduced transfusions and costs. In 2008, the Western Australia Department of Health initiated a comprehensive health-system–wide PBM program. This study assesses program outcomes. STUDY DESIGN AND METHODS This was a retrospective study of 605,046 patients admitted to four major adult tertiary-care hospitals between July 2008 and June 2014. Outcome measures were red blood cell (RBC), fresh-frozen plasma (FFP), and platelet units transfused; single-unit RBC transfusions; pretransfusion hemoglobin levels; elective surgery patients anemic at admission; product and activity-based costs of transfusion; in-hospital mortality; length of stay; 28-day all-cause emergency readmissions; and hospital-acquired complications. RESULTS Comparing final year with baseline, units of RBCs, FFP, and platelets transfused per admission decreased 41% (p

Few studies have investigated if, and how, red cell transfusion and anaemia interact. We analysed 60,955 admissions to three metropolitan hospitals in Western Australia between 2008 and 2017 to determine whether the relationship between red cell transfusion and outcomes in surgical patients differed by lowest (nadir) level of haemoglobin. At levels above 100 g.l-1 , in-hospital, 30-day and 1-year mortality were higher with transfusion, the adjusted odds ratios (ORs) (95%CI) being 8.80 (4.43-17.45) p < 0.001 and 3.68 (1.93-7.02) p < 0.001 and the adjusted hazard ratio (95%CI) being 1.83 (1.28-2.61) p = 0.001, respectively. Likewise, between 90 g.l-1 and 99 g.l-1 , in-hospital, 30-day and 1-year mortality were higher with transfusion, the adjusted odds ratio (95%CI) being 3.76 (2.23-6.34) p < 0.001 and 1.96 (1.23-3.12) p < 0.001 and the adjusted hazard ratio (95%CI) being 1.34 (1.05-1.70) p = 0.017, respectively. Length of stay was longer with transfusion at nadir haemoglobin levels above 100 g.l-1 and in the following ranges: 90-99 g.l-1 , 80-89 g.l-1 , 70-79 g.l-1 and 60-69 g.l-1 , the adjusted rate ratio (95%CI) being 1.38 (1.25-1.53) p < 0.001, 1.18 (1.10-1.27) p < 0.001, 1.17 (1.13-1.22) p < 0.001, 1.07 (1.02-1.12) p = 0.003 and 1.24 (1.13-1.36) p < 0.001, respectively. Mortality was higher with red cell transfusion at haemoglobin levels greater than 90 g.l-1 , whereas at all levels below 90 g.l-1 mortality was not significantly higher or lower. Length of stay was longer with transfusion at nadir haemoglobin levels of 60 g.l-1 or above. Our results suggest that nadir haemoglobin modified the relationship between red cell transfusion and outcomes and adds to the evidence recommending caution before transfusing red cells.

To determine whether a multidisciplinary, multimodal Patient Blood Management (PBM) program for patients undergoing surgery is effective in reducing perioperative complication rate, and thereby is effective in improving clinical outcome.PBM is a medical concept with the focus on a comprehensive anemia management, to minimize iatrogenic (unnecessary) blood loss, and to harness and optimize patient-specific physiological tolerance of anemia.A systematic review and meta-analysis was performed. Eligible studies had to address each of the 3 PBM pillars with at least 1 measure per pillar, for example, preoperative anemia management plus cell salvage plus rational transfusion strategy. The study protocol has been registered with PROSPERO (CRD42017079217).Seventeen studies comprising 235,779 surgical patients were included in this meta-analysis (100,886 pre-PBM group and 134,893 PBM group). Implementation of PBM significantly reduced transfusion rates by 39% [risk ratio (RR) 0.61, 95% confidence interval (CI) 0.55-0.68, P0.00001], 0.43 red blood cell units per patient (mean difference -0.43, 95% CI -0.54 to -0.31, P0.00001), hospital length of stay (mean difference -0.45, 95% CI -0.65 to -0.25, P0,00001), total number of complications (RR 0.80, 95% CI 0.74-0.88, P0.00001), and mortality rate (RR 0.89, 95% CI 0.80-0.98, P = 0.02).Overall, a comprehensive PBM program addressing all 3 PBM pillars is associated with reduced transfusion need of red blood cell units, lower complication and mortality rate, and thereby improving clinical outcome. Thus, this first meta-analysis investigating a multimodal approach should motivate all executives and health care providers to support further PBM activities.

Postpartum haemorrhage (PPH) is the leading cause of maternal mortality and morbidity globally. Obstetric bleeding can be catastrophic and management is challenging, involving a coordinated multidisciplinary approach, which may include blood products. In settings where blood transfusion is not an option, either because of patient refusal (most commonly in Jehovah Witnesses) or because of unavailability of blood, management becomes even more challenging. Observational studies have demonstrated an association between refusal of blood products in major obstetric haemorrhage and increased morbidity and mortality. This review draws upon evidence in the literature, physiological principles and expert opinion for strategies and guidance to optimise the outcomes of pregnant women in whom blood transfusion is either refused or impossible. The importance of a multidisciplinary antenatal and perinatal management plan, including optimisation of haemoglobin and iron stores pre-delivery, blood loss minimisation, early haemorrhage control and postpartum anaemia treatment, is discussed.

In July 2008, the Western Australia (WA) Department of Health embarked on a landmark 5-year project to implement a sustainable comprehensive health-system-wide Patient Blood Management Program. Fundamentally, it was a quality and safety initiative, which also had profound resource and economic implications. Unsustainable escalating direct and indirect costs of blood, potentially severe blood shortages due to changing population dynamics, donor deferrals, loss of altruism, wide variations in transfusion practice and growing knowledge of transfusion limitations and adverse outcomes necessitate a paradigm shift in the management of anemia and blood loss. The concept of patient-focused blood management is proving to be an effective force for change. This approach has now evolved to embrace comprehensive hospital-wide Patient Blood Management Programs. These programs show significant reductions in blood utilisation, and costs while achieving similar or improved patient outcomes. The WA Program is achieving these outcomes across a health jurisdiction in a sustained manner.

BACKGROUND: Red blood cell (RBC) transfusion is independently associated in a dose-dependent manner with increased intensive care unit stay, total hospital length of stay, and hospital-acquired complications. Since little is known of the cost of these transfusionassociated adverse outcomes our aim was to determine the total hospital cost associated with RBC transfusion and to assess any dose-dependent relationship. STUDY DESIGN AND METHODS: A retrospective cohort study of all multiday acute care inpatients discharged from a five hospital health service in Western Australia between July 2011 and June 2012 was conducted. Main outcome measures were incidence of RBC transfusion and mean inpatient hospital costs. RESULTS: Of 89,996 multiday, acute care inpatient discharges, 4805 (5.3%) were transfused at least 1 unit of RBCs. After potential confounders were adjusted for, the mean inpatient cost was 1.83 times higher in the transfused group compared with the nontransfused group (95% confidence interval, 1.78-1.89; p < 0.001). The estimated total hospital-associated cost of RBC transfusion in this study was AUD $77 million (US $72 million), representing 7.8% of total hospital expenditure on acute care inpatients. There was a significant dosedependent association between the number of RBC units transfused and increased costs after adjusting for confounders. CONCLUSION: RBC transfusions were independently associated with significantly higher hospital costs. The financial implication to hospital budgets will assist in prioritizing areas to reduce the rate of RBC transfusions and in implementing patient blood management programs. I n 2008 the Western Australian (WA) State Health Executive Forum approved a 5-year project to implement a comprehensive patient blood management (PBM) program. The aim of the program was to change transfusion practice in WA public hospitals, with the literature showing PBM programs can improve patient outcomes and reduce costs. The statewide program has already shown that PBM strategies are associated with reduced transfusions. 1,2 The improved perioperative

IntroductionThere has been a significant increase in the number of systematic reviews and meta-analyses of randomised controlled trials investigating thresholds for red blood cell transfusion. To systematically collate, appraise and synthesise the results of these systematic reviews and meta-analyses, we will conduct an overview of systematic reviews.Methods and analysisThis is a protocol for an overview of systematic reviews. We will search five databases: MEDLINE, Embase, Web of Science Core Collection, PubMed (for prepublication, in process and non-Medline records) and Google Scholar. We will consider systematic reviews and meta-analyses of randomised controlled trials evaluating the effect of haemoglobin thresholds for red blood cell transfusion on mortality. Two authors will independently screen titles and abstracts retrieved in the literature search and select studies meeting the eligibility criteria for full-text review. We will extract data onto a predefined form designed to summarise the key characteristics of each review. We will assess the methodological quality of included reviews and the quality of evidence in included reviews.Ethics and disseminationFormal ethics approval is not required for this overview as we will only analyse published literature. The findings of this study will be presented at relevant conferences and submitted for peer-review publication. The results are likely to be used by clinicians, policy makers and developers of clinical guidelines and will inform suggestions for future systematic reviews and randomised controlled trials.PROSPERO registration numberCRD42019120503.

For more than 70 years the default therapy for anaemia and blood loss was mostly transfusion. Accumulating evidence demonstrates a significant dose-dependent relationship between transfusion and adverse outcomes. This and other transfusion-related challenges led the way to a new paradigm. Patient blood management (PBM) is the application of evidence-based practices to optimise patient outcomes by managing and preserving the patient's own blood. 'Real-world' studies have shown that PBM improves patient outcomes and saves money. The prevalence of anaemia in adult South Africans is 31% in females and 17% in males. Improving the management of anaemia will firstly improve public health, secondly relieve the pressure on the blood supply, and thirdly improve the productivity of the nation's workforce. While high-income countries are increasingly implementing PBM, many middle- and low-income countries are still trying to upscale their transfusion services. The implementation of PBM will improve South Africa's health status while saving costs.

Background We describe the implementation and impact of a patient blood management program (PBMP) in an Australian teaching hospital. Study Design and Methods A PBMP was introduced at a single tertiary care hospital in 2009 as a pilot for the Western Australian Health Department statewide PBMP. The first 3 years of interventions aimed to make effective use of preoperative clinics, manage perioperative anemia, improve perioperative hemostasis, reduce blood sample volumes, and implement restrictive transfusion triggers and a single-unit transfusion policy. Results Between 2008 and 2011, admissions to Fremantle Hospital and Health Services increased by 22%. Using 2008 as a reference year, the mean number of red blood cell (RBC) units per admission declined 26% by 2011. Use of fresh-frozen plasma and platelets showed 38 and 16% declines, respectively. Cryoprecipitate increased 7% over the 4-year period. For elective admissions between 2008 and 2011, the leading decline in RBC transfusion rate was seen in cardiothoracic surgery (27.5% to 12.8%). The proportion of single RBC unit use increased from 13% to 28% (p

The aim of this paper is to describe a linked patient blood management (PBM) data system and to demonstrate its usefulness by presenting the blood usage data obtained. Our existing datasets already collected much of the required information in relation to PBM. However, these datasets were not linked. A patient identifier was used to link the Patient Administration System with the Laboratory Information System. Data linkage was achieved by linking the Laboratory Information System with the Patient Administration System records where blood transfusion or laboratory result date/time fell between admission and discharge date/time. The two datasets were then consolidated into the PBM data system. Blood usage data obtained from the system showed that between August 2008 and July 2009 there were 59,627 patient completed separations in the pilot hospital. Of the total transfused units, 62% were red blood cells (RBC), followed by fresh frozen plasma (22%), cryoprecipitate (9%) and platelets (8%). Around 50% of RBC transfusions were administered to patients >70 years of age. General medicine represented 21% of RBC usage, followed by haematology (19%), orthopaedics (17%) and general surgery (16%). Patients with 100 g/l pre-transfusion haemoglobin received 9% of RBC transfusions and patients with 71-100 g/l pre-transfusion haemoglobin received 73% of RBC transfusions. The post-transfusion haemoglobin in RBC transfusions exceeded 100 g/l in 33% of patients. Databases were successfully linked to produce a powerful tool to monitor blood utilisation and transfusion practices within a pilot PBM program. This will facilitate effective targeting of PBM strategies and ongoing monitoring of their impact.

In times of escalating health-care cost, it is of great importance to carefully assess the cost-effectiveness and appropriateness of the most resource-consuming health interventions. A long-standing and common clinical practice that has been underestimated in cost and overestimated in effectiveness is the transfusion of allogeneic blood products. Studies show that this intervention comes with largely underestimated service cost and unacceptably high utilisation variability for matched patients, thus adding billions of unnecessary dollars to the health-care expenditure each year. Moreover, a large and increasing body of literature points to a dose-dependent increase of morbidity and mortality and adverse long-term outcomes associated with transfusion whereas published evidence for benefit is extremely limited. This means that transfusion may be a generator for increased hospital stay and possible re-admissions, resulting in additional billions in unnecessary expenditure for the health system. In contrast to this, there are evidence-based and cost-effective treatment options available to pre-empt and reduce allogeneic transfusions. The patient-specific rather than a product-centred application of these multiple modalities is termed patient blood management (PBM). From a health-economic perspective, the expeditious implementation of PBM programmes is clearly indicated. Both patients and payers could benefit from this concept that has recently been endorsed through the World Health Assembly resolution WHA63.12.

Both anaemia and allogenic red blood cell transfusion are common and potentially harmful in patients admitted to the intensive care unit. Whilst intravenous iron may decrease anaemia and RBC transfusion requirement, the safety and efficacy of administering iron intravenously to critically ill patients is uncertain. The multicentre, randomized, placebo-controlled, blinded Intravenous Iron or Placebo for Anaemia in Intensive Care (IRONMAN) study was designed to test the hypothesis that, in anaemic critically ill patients admitted to the intensive care unit, early administration of intravenous iron, compared with placebo, reduces allogeneic red blood cell transfusion during hospital stay and increases the haemoglobin level at the time of hospital discharge. Of 140 patients enrolled, 70 were assigned to intravenous iron and 70 to placebo. The iron group received 97 red blood cell units versus 136 red blood cell units in the placebo group, yielding an incidence rate ratio of 0.71 [95 % confidence interval (0.43–1.18), P = 0.19]. Overall, median haemoglobin at hospital discharge was significantly higher in the intravenous iron group than in the placebo group [107 (interquartile ratio IQR 97–115) vs. 100 g/L (IQR 89–111), P = 0.02]. There was no significant difference between the groups in any safety outcome. In patients admitted to the intensive care unit who were anaemic, intravenous iron, compared with placebo, did not result in a significant lowering of red blood cell transfusion requirement during hospital stay. Patients who received intravenous iron had a significantly higher haemoglobin concentration at hospital discharge. The trial was registered at http://www.anzctr.org.au as # ACTRN12612001249842.

Evidence-based patient blood management (PBM) is aimed at achieving better patient outcomes by relying on a patient's own blood rather than on donor blood. This review covers the rationale behind PBM, the treatment modalities involved and the drivers to adopt PBM as a new standard of care.Transfusion rates vary significantly between comparable countries; they also vary between centers for matched patients in standardized elective surgical interventions. Preoperative anemia, perioperative blood loss and liberal transfusion triggers are the main predictors for transfusion and pose risks to the patient. PBM is mitigating these risks by optimizing the patient's native red cell mass, minimizing blood loss, optimizing the physiological reserve of anemia and preempting transfusions. A growing number of studies show that transfusion is associated in a dose-dependent relationship with increased morbidity, mortality and hospital length of stay. Evidence suggests that this relationship is not merely associative but causal. Furthermore, the over-ageing population of the developed world leads to a growing gap between supply and demand of blood, the safety of donor blood remains unpredictable and the cost of transfusion is much higher than previously estimated.High transfusion variability, adverse transfusion outcomes, limited evidence for the benefit of transfusion particularly in elective patients and high cost of transfusion are challenging the traditional transfusion paradigm. National and state-wide initiatives are underway in Australia to broadly implement PBM and PBM programs as a new and cost-effective standard of care in the public health system.

The transfusion of allogeneic red blood cells (RBCs) and other blood components is ingrained in modern medical practice. The rationale for administering transfusions is based on key assumptions that efficacy is established and risks are acceptable and minimized. Despite the cliché that, "the blood supply is safer than ever," data about risks and lack of efficacy of RBC transfusions in several clinical settings have steadily accumulated. Frequentist statisticians and clinicians demand evidence from randomized clinical trials (RCTs); however, causation for the recognized serious hazards of allogeneic transfusion has never been established in this manner. On the other hand, the preponderance of evidence implicating RBC transfusions in adverse clinical outcomes related to immunomodulation and the storage lesion comes from observational studies, and a broad and critical analysis to evaluate causation is overdue. It is suggested in several circumstances that this cannot wait for the design, execution, and conduct of rigorous RCTs. We begin by examining the nature and definition of causation with relevant examples from transfusion medicine. Deductive deterministic methods may be applied to most of the well-accepted and understood serious hazards of transfusion, with modified Koch's postulates being fulfilled in most circumstances. On the other hand, when several possible interacting risk factors exist and RBC transfusions are associated with adverse clinical outcomes, establishing causation requires inferential probabilistic methodology. In the latter circumstances, the case for RBC transfusions being causal for adverse clinical outcomes can be strengthened by applying modified Bradford Hill criteria to the plethora of existing observational studies. This being the case, a greater precautionary approach to RBC transfusion is necessary and equipoise that justifying RCTs may become problematic.

The objective of this paper is to introduce clinicians and health care professionals to the concept of patient blood management (PBM) and to explain the difference between PBM and the concept of “appropriate use” of blood products. The five reasons why modern health systems need to shift from product-focused transfusion practice to PBM are also presented. These are: the aging population with a leveraged demand for blood products opposed to a shrinking donor base; the growing awareness that transfusion is a complex service involving many different cost centers within a hospital and representing a multiple of the blood product cost; the continuous effort to protect blood pools from known, new, or re-emerging pathogens while facing uncertainty over their potentially long silent carrier states; the emerging evidence that transfusion is an independent risk factor for adverse outcomes; and finally, a lack of evidence for benefit of transfusion for the vast majority of recipients.

A. Hofmann, S. Farmer & A. Shander Medical Society for Blood Management, Laxenburg, Austria Centre for Population Health Research, Curtin Health Innovation Research Institute (CHIRI), Curtin University, Western Australia; Medical Society for Blood Management, Glen Forrest, WA, Australia Department of Anesthesiology and Critical Care and Hyperbaric Medicine; The Institute for the Patient Blood Management and Bloodless Medicine and Surgery at Englewood Hospital and Medical Center, Englewood, NJ, USA; Anesthesiology & Medicine at Mt. Sinai School of Medicine, New York City, NY, USA

Background. Patient blood management (PBM) programs are associated with reduced transfusion usage, reduced hospital costs, and improved patient outcomes. The application of PBM principles in patients with malignant disease might achieve similar results. However, this population presents unique challenges. The aim of the present study was to investigate the impact of a PBM program on blood usage and patient outcomes in cancer patients, particularly in the setting of restricted use of erythropoiesis-stimulating agents (ESAs). Materials and Methods. A retrospective observational study was performed of patients admitted with a primary diagnosis of malignancy treated at Eastern Maine Medical Center as inpatients or outpatients, or both, from January 2008 through July 2013. Results. The proportion of inpatients and outpatients receiving ESAs decreased from 2.9% in 2008 to 1.1% in 2013 (p < .001). During the same period, an increase occurred in the mean dose of intravenous (IV) iron from 447 mg (95% confidence interval [CI], 337–556) to 588 mg (95% CI, 458–718). The mean red blood cell (RBC) units transfused per inpatient and outpatient episode decreased from 0.067 to 0.038 unit (p < .001). In inpatients, significant increases occurred in the proportion of single-unit RBC transfusions (p < .001) and patients infused with IV iron (p = .02), and significant decreases in the mean pretransfusion hemoglobin (p = .02) and RBC transfusion rate (p = .04). In-hospital mortality and length of stay did not change significantly during this period. Conclusion. Despite the decreased use of ESA therapy, the implementation of a PBM program and outpatient anemia management protocol in cancer patients at our medical center was associated with significant reductions in RBC usage.

Background As defined by evidence-based medicine randomized controlled trials rank higher than observational studies in the hierarchy of clinical research. Accordingly, when assessing the effects of treatments on patient outcomes, there is a tendency to focus on the study method rather than also appraising the key elements of study design. A long-standing debate regarding findings of randomized controlled trials compared with those of observational studies, their strengths and limitations and questions regarding causal inference, has recently come into focus in relation to research assessing patient outcomes in transfusion medicine. Discussion Observational studies are seen to have limitations that are largely avoided with randomized controlled trials, leading to the view that observational studies should not generally be used to inform practice. For example, observational studies examining patient outcomes associated with blood transfusion often present higher estimates of adverse outcomes than randomized controlled trials. Some have explained this difference as being a result of observational studies not properly adjusting for differences between patients transfused and those not transfused. However, one factor often overlooked, likely contributing to these variances between study methods is different exposure criteria. Another common to both study methods is exposure dose, specifically, measuring units transfused during only a part of the patient’s hospital stay. Summary When comparing the results of observational studies with randomized controlled trials assessing transfusion outcomes it is important that one consider not only the study method, but also the key elements of study design. Any study, regardless of its method, should focus on accurate measurement of the exposure and outcome variables of interest. Failure to do so may subject the study, regardless of its type, to bias and the need to interpret the results with caution.

The application of blood conservation strategies to minimise or avoid allogeneic blood transfusion is seen internationally as a desirable objective. Bloodless surgery is a relatively new practice that facilitates that goal. However, the concept is either poorly understood or evokes negative connotations. Bloodless surgery is a term that has evolved in the medical literature to refer to a peri-operative team approach to avoid allogeneic transfusion and improve patient outcomes. Starting as an advocacy in the early 1960s, it has now grown into a serious practice being embraced by internationally respected clinicians and institutions. Central to its success is a coordinated multidisciplinary approach. It encompasses the peri-operative period with surgeons, anaesthetists, haematologists, intensivists, pathologists, transfusion specialists, pharmacists, technicians, and operating room and ward nurses utilising combinations of the numerous blood conservation techniques and transfusion alternatives now available. A comprehensive monograph on the subject of bloodless surgery along with detailed coverage of risks and benefits of each modality (some modalities are discussed in more detail elsewhere in this issue) is beyond the scope of this article. Accordingly, a brief overview of the history, theory and practice of bloodless surgery is presented, along with the clinical and institutional management requirements.

Lower preoperative haemoglobin and older age pose a risk for perioperative allogeneic blood transfusions (ABT). The presence of chronic kidney disease (CKD) is associated with low haemoglobin, greater bleeding and ABT utilization.The interaction between estimated glomerular filtration rate (eGFR) and haemoglobin on perioperative ABT, length-of-stay and mortality was assessed in 86 patients with CKD stage 3 or higher undergoing elective total knee or hip arthroplasty compared with 294 without CKD. Multivariate analyses for ABT risk with haemoglobin, eGFR, age, gender, duration of surgery and primary versus revision surgery were performed.Patients with CKD had lower preoperative haemoglobin and higher incidence of ABT. Haemoglobin was independently associated with increased odds of ABT (0.74 (95% confidence interval 0.71-0.77), P = 0.001), but eGFR was not (0.98 (0.96-1.02), P = 0.089). Length-of-stay and 1 year mortality did not differ between non-transfused CKD patients and controls. Transfused CKD patients had significantly higher length-of-stay compared with transfused controls (25 ± 21 vs 19 ± 16 days, P 0.0001), although 1 year mortality between transfused CKD patients and controls did not differ significantly.CKD alone, in the absence of anaemia, does not predispose to increased risk of ABT or length-of-stay in patients with mild-to-moderate CKD undergoing elective joint surgery. However, low haemoglobin is associated with increased ABT utilization and increased length-of-stay. Considering that 1 in 4 patients undergoing elective hip or knee arthroplasty has CKD, optimal preoperative patient blood management may improve outcome in this population.

Patient blood management is now high on national and international health-system agendas. Serious supply challenges as a result of changing population dynamics, escalating cost of blood, ongoing safety challenges and questions about transfusion efficacy and outcomes are necessitating change in transfusion practice. Numerous initiatives are underway to bring about change, including the institution of comprehensive patient blood management programmes. In 2008, the Western Australia Department of Health initiated a 5-year project to implement a comprehensive health-system-wide Patient Blood Management Program with the aim of improving patient outcomes while reducing costs. Clinically, the Program was structured on the three pillars of patient blood management, namely (1) optimising the patient's own red cell mass, (2) minimising blood loss and (3) harnessing and optimising the patient-specific anaemia reserve. It employs multiple strategies to bring about a cultural change from a blood-product focus to a patient focus. This Program was undertaken in a State that already had one of the lowest red blood cell issuance rates per 1000 population in the developed world (30.47 red blood cell units per 1000 population). The Program identified reasons and drivers for practice change. From financial years 2008–09 to 2011–12, issuance has progressively decreased in Western Australia to 27.54 units per 1000. During the same years, despite increasing activity, total issuance of red blood cells to the entire State decreased from 70,103 units to 65,742. Nationally and internationally, other initiatives are underway to bring about change and implement patient blood management. The World Health Assembly in May 2010 adopted resolution WHA63.12 endorsing patient blood management and its three-pillar application. The United States Advisory Committee on Blood Safety and Availability met in 2011 to consider the implications of this resolution and its implementation.

We describe the implementation and impact of a patient blood management program (PBMP) in an Australian teaching hospital.A PBMP was introduced at a single tertiary care hospital in 2009 as a pilot for the Western Australian Health Department statewide PBMP. The first 3 years of interventions aimed to make effective use of preoperative clinics, manage perioperative anemia, improve perioperative hemostasis, reduce blood sample volumes, and implement restrictive transfusion triggers and a single-unit transfusion policy.Between 2008 and 2011, admissions to Fremantle Hospital and Health Services increased by 22%. Using 2008 as a reference year, the mean number of red blood cell (RBC) units per admission declined 26% by 2011. Use of fresh-frozen plasma and platelets showed 38 and 16% declines, respectively. Cryoprecipitate increased 7% over the 4-year period. For elective admissions between 2008 and 2011, the leading decline in RBC transfusion rate was seen in cardiothoracic surgery (27.5% to 12.8%). The proportion of single RBC unit use increased from 13% to 28% (p 0.001), and the proportion of double units decreased from 48% to 37% (p 0.001).This is the first tertiary hospital in Australia to establish a multidisciplinary multimodal PBMP. Interventions across disciplines resulted in decreased use of RBC units especially in orthopedic and cardiothoracic surgery. Continuing education and feedback to specialties will maintain the program, improve patient outcomes, and decrease the transfusion rate.

An international multidisciplinary panel of 15 experts reviewed 494 published articles and used the RAND/UCLA Appropriateness Method to determine the appropriateness of allogeneic red blood cell (RBC) transfusion based on its expected impact on outcomes of stable nonbleeding patients in 450 typical inpatient medical, surgical, or trauma scenarios. Panelists rated allogeneic RBC transfusion as appropriate in 53 of the scenarios (11.8%), inappropriate in 267 (59.3%), and uncertain in 130 (28.9%). Red blood cell transfusion was most often rated appropriate (81%) in scenarios featuring patients with hemoglobin (Hb) level 7.9 g/dL or less, associated comorbidities, and age older than 65 years. Red blood cell transfusion was rated inappropriate in all scenarios featuring patients with Hb level 10 g/dL or more and in 71.3% of scenarios featuring patients with Hb level 8 to 9.9 g/dL. Conversely, no scenario with patient's Hb level of 8 g/dL or more was rated as appropriate. Nearly one third of all scenarios were rated uncertain, indicating the need for more research. The observation that allogeneic RBC transfusions were rated as either inappropriate or uncertain in most scenarios in this study supports a more judicious transfusion strategy. In addition, the large number of scenarios in which RBC transfusions were rated as uncertain can serve as a road map to identify areas in need of further investigation.