Penny-wise and pound-foolish: the challenges of preoperative anaemia management.

The timely correction of anaemia before major surgery is important for optimising perioperative patient outcomes. However, multiple barriers have precluded the global expansion of preoperative anaemia treatment programmes, including misconceptions about the true cost/benefit ratio for patient care and health system economics. Institutional investment and buy-in from stakeholders could lead to significant cost savings through avoided complications of anaemia and red blood cell transfusions, and through containment of direct and variable costs of blood bank laboratories. In some health systems, billing for iron infusions could generate revenue and promote growth of treatment programmes. The aim of this work is to galvanise integrated health systems worldwide to diagnose and treat anaemia before major surgery.

Patients' Choice, Consent, and Ethics in Patient Blood Management.

The goal of patient blood management (PBM) is to optimize clinical outcomes for individual patients by managing their blood as a precious and unique resource to be safeguarded and managed judiciously. A corollary to successful PBM is the minimization or avoidance of blood transfusion and stewardship of donated blood. The first is achieved by a multidisciplinary approach with personalized management plans shared and decided on with the patient or their substitute. It follows that the physician-patient relationship is an integral component of medical practice and the fundamental link between patient and doctor based on trust and honest communication. Central to PBM is accurate and timely diagnosis based on sound physiology and pathophysiology as the bedrock on which scientifically based medicine is founded. PBM in all disease contexts starts with the questions, "What is the status of the patient's blood?" "If there are specific abnormalities in the blood, how should they be managed?" and "If allogeneic blood transfusion is considered, is there no reasonable alternative therapy?" There are compelling scientific reasons to implement a nontransfusion default position when there is clinical uncertainty and questionable evidence of clinical efficacy for allogeneic blood transfusion due to known potential hazards. Patients must be informed of their diagnosis, the nature, severity and prognosis of the disease, and treatment options along with risks and benefits. They should be involved in decision-making regarding their management. However, as part of this process, there are multifaceted medical, legal, ethical, and economic issues, encompassing shared decision-making, patient choice, and informed consent. Furthermore, variability in patient circumstances and preferences, the complexity of medical science, and the workings of health care systems in which consent takes place can be bewildering, not only for the patient but also for clinicians obtaining consent. Adding "patient" to the concept of blood management differentiates it from "donor" blood management to avoid confusion and the perception that PBM is a specific medical intervention. Personalized PBM is tailoring the PBM to the specific characteristics of each patient. With this approach, there should be no difficulty addressing the informed consent and ethical aspects of PBM. Patients can usually be reassured that there is nothing out of order with their blood, in which case the focus of PBM is to keep it that way. In some circumstances, a hematologist may be involved as a patient's blood advocate when abnormalities require expert involvement while the primary disease is being managed.

Patient Blood Management: Improving Outcomes for Millions While Saving Billions. What Is Holding It Up?

Patient blood management (PBM) offers significantly improved outcomes for almost all medical and surgical patient populations, pregnant women, and individuals with micronutrient deficiencies, anemia, or bleeding. It holds enormous financial benefits for hospitals and payers, improves performance of health care providers, and supports public authorities to improve population health. Despite this extraordinary combination of benefits, PBM has hardly been noticed in the world of health care. In response, the World Health Organization (WHO) called for its 194 member states, in its recent Policy Brief, to act quickly and decidedly to adopt national PBM policies. To further support the WHO's call to action, this article addresses 3 aspects in more detail. The first is the urgency from a health economic perspective. For many years, growth in health care spending has outpaced overall economic growth, particularly in aging societies. Due to competing economic needs, the continuation of disproportionate growth in health care spending is unsustainable. Therefore, the imperative for health care leaders and policy makers is not only to curb the current spending rate relative to the gross domestic product (GDP) but also to simultaneously improve productivity, quality, safety of patient care, and the health status of populations. Second, while PBM meets these requirements on an exceptional scale, uptake remains slow. Thus, it is vital to identify and understand the impediments to broad implementation. This includes systemic challenges such as the so-called "waste domains" of failure of care delivery caused by malfunctions of health care systems, failure of care coordination, overtreatment, and low-value care. Other impediments more specific to PBM are the misperception of PBM and deeply rooted cultural patterns. Third, understanding how the 3Es-evidence, economics, and ethics-can effectively be used to motivate relevant stakeholders to take on their respective roles and responsibilities and follow the urgent call to implement PBM as a standard of care.

Reflections on pandemics and the 60th anniversary of the University of New South Wales Medical School.

In March 1961 the University of New South Wales enrolled the first students into the new faculty of medicine that is now ranked 4th in Australia and 59th in the world. The author was fortunate to be a member of that pioneering group and looks back in gratitude to all the visionary and committed academics and mentors, who made this happen. Many of the foundation academics were fellows of the Royal Australasian College of Physicians, with two becoming University of New South Wales deans of medicine. One-quarter of the foundation year's graduates became fellows of the college and the first PhD medical graduate, Professor John Chalmers AC, became president of the college.

Physician autonomy and patient rights: lessons from an enforced blood transfusion and the role of patient blood management.

This article provides an ethical and medico-legal analysis of ruling no. 465 of 30 May 2018 issued by the Court of Termini Imerese (Palermo) and confirmed on appeal on 11 November 2020, which, in the absence of similar historical precedents in Europe, convicted a medical doctor of a crime of violent assault for having ordered the administration of a blood transfusion to a patient specifically declining blood transfusion on religious grounds. We analyse the Court's decision regarding the identification of assault in performing the blood transfusion and its decision not to accept exculpatory urgent 'necessity' as a defence. In addition, we present an updated revision of the current standard of care in transfusion medicine as well as the ethical principles governing the patient's declining of transfusion. In doing so, we highlight that respect for the patient's self-determination in declining transfusions and respect for the professional autonomy of the doctor protecting the safety and life of the patient could be equally satisfied by applying the current peer-reviewed evidence.

Systematic reviews and meta-analyses comparing mortality in restrictive and liberal haemoglobin thresholds for red cell transfusion: an overview of systematic reviews.

BACKGROUND: There are no overviews of systematic reviews investigating haemoglobin thresholds for transfusion. This is important as the literature on transfusion thresholds has grown considerably in recent years. Our aim was to synthesise evidence from systematic reviews and meta-analyses of the effects of restrictive and liberal transfusion strategies on mortality. METHODS: This was a systematic review of systematic reviews (overview). We searched MEDLINE, Embase, Web of Science Core Collection, PubMed, Google Scholar, and the Joanna Briggs Institute EBP Database, from 2008 to 2018. We included systematic reviews and meta-analyses of randomised controlled trials comparing mortality in patients assigned to red cell transfusion strategies based on haemoglobin thresholds. Two independent reviewers extracted data and assessed methodological quality. We assessed the methodological quality of included reviews using AMSTAR 2 and the quality of evidence pooled using an algorithm to assign GRADE levels. RESULTS: We included 19 systematic reviews reporting 33 meta-analyses of mortality outcomes from 53 unique randomised controlled trials. Of the 33 meta-analyses, one was graded as high quality, 15 were moderate, and 17 were low. Of the meta-analyses presenting high- to moderate-quality evidence, 12 (75.0%) reported no statistically significant difference in mortality between restrictive and liberal transfusion groups and four (25.0%) reported significantly lower mortality for patients assigned to a restrictive transfusion strategy. We found few systematic reviews addressed clinical differences between included studies: variation was observed in haemoglobin threshold concentrations, the absolute between group difference in haemoglobin threshold concentration, time to randomisation (resulting in transfusions administered prior to randomisation), and transfusion dosing regimens. CONCLUSIONS: Meta-analyses graded as high to moderate quality indicate that in most patient populations no difference in mortality exists between patients assigned to a restrictive or liberal transfusion strategy. TRIAL REGISTRATION: PROSPERO CRD42019120503.

Essential Role of Patient Blood Management in a Pandemic: A Call for Action.

The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Global health care now faces unprecedented challenges with widespread and rapid human-to-human transmission of SARS-CoV-2 and high morbidity and mortality with COVID-19 worldwide. Across the world, medical care is hampered by a critical shortage of not only hand sanitizers, personal protective equipment, ventilators, and hospital beds, but also impediments to the blood supply. Blood donation centers in many areas around the globe have mostly closed. Donors, practicing social distancing, some either with illness or undergoing self-quarantine, are quickly diminishing. Drastic public health initiatives have focused on containment and "flattening the curve" while invaluable resources are being depleted. In some countries, the point has been reached at which the demand for such resources, including donor blood, outstrips the supply. Questions as to the safety of blood persist. Although it does not appear very likely that the virus can be transmitted through allogeneic blood transfusion, this still remains to be fully determined. As options dwindle, we must enact regional and national shortage plans worldwide and more vitally disseminate the knowledge of and immediately implement patient blood management (PBM). PBM is an evidence-based bundle of care to optimize medical and surgical patient outcomes by clinically managing and preserving a patient's own blood. This multinational and diverse group of authors issue this "Call to Action" underscoring "The Essential Role of Patient Blood Management in the Management of Pandemics" and urging all stakeholders and providers to implement the practical and commonsense principles of PBM and its multiprofessional and multimodality approaches.

Channelling medical truths from Sir William Osler.

Dr James L. T. Isbister (JLT), a graduate of the University of Adelaide, came to Sydney as a clinical pathologist at Sydney Hospital in 1897 and subsequently was a general practitioner in North Sydney and honorary surgeon and gynaecologist at Royal North Shore Hospital from 1900. He owned the first motor vehicle in North Sydney and he was Mary MacKillops's local doctor during her last years at the Sisters of St Joseph of the Sacred Heart convent in North Sydney. On a visit to the United Kingdom in 1908, he met Sir William Osler, a meeting that clearly impacted on his thinking that has been channelled down the Isbister medical family for over a century. JLT was a founding member of the Royal Australasian College of Surgeons with a grandson, Peter, also becoming a fellow. His son, James, daughter-in-law, Clair, and grandson, James, became fellows of the Royal Australasian College of Physicians. More recently, his great-grand daughter is currently an advanced college trainee. In this historical perspective, JLT's grandson confirms that Osler's medical truths have been channelled, added to and practised by JLT and his descendants.

Age of blood and adverse outcomes in a maternity population.

BACKGROUND: In recent times there has been debate around whether longer storage time of blood is associated with increased rates of adverse outcomes after transfusion. It is unclear whether results focused on cardiac or critically ill patients apply to a maternity population. This study investigates whether older blood is associated with increased morbidity and readmission in women undergoing obstetric transfusion. STUDY DESIGN AND METHODS: Women giving birth in hospitals in New South Wales, Australia, between July 2006 and December 2010 were included in the study population if they had received between 1 and 4 red blood cell units during the birth admission. Information on women's characteristics, transfusions, and outcomes were obtained from five routinely collected data sets including blood collection, birth, and hospitalization data. Generalized propensity score methods were used to determine the effect of age of blood on rates of severe morbidity and readmission, independent of confounding factors. RESULTS: Transfusion data were available for 2990 women, with a median age of blood transfused of 20 days (interquartile range, 14-27 days). There were no differences in the maximum age of blood transfused between women with and without severe morbidity (21 [14-28] days vs. 22 [15-30] days) and in women readmitted or not (22 [14-28] days vs. 22 [16-30] days). After potential confounding factors were considered, no relationship was found between the age of blood transfused and rates of severe morbidity and readmission. CONCLUSION: Among women receiving low-volume transfusions during a birth admission, there was no evidence of increased rates of adverse outcomes after transfusion with older blood.

Red cell and platelet transfusions in neonates: a population-based study.

OBJECTIVES: This study aimed to describe the use of red cells, platelets and exchange transfusions among all neonates in a population cohort, to examine trends in transfusion over time and to determine transfusion rates in at-risk neonates. DESIGN: Linked population-based birth and hospital data from New South Wales (NSW), Australia, were used to determine rates of blood product transfusion in the first 28 days of life. The study included all live births ≥23 weeks' gestation in NSW between 2001 and 2011. RESULTS: Between 2001 and 2011, 5326 of 989 491 live born neonates received a red cell, platelet or exchange transfusion (5.4/1000 births). Transfusion rates were 4.8 per 1000 for red cells, 1.3 per 1000 for platelets and 0.3 per 1000 for exchange transfusion. Overall transfusion rate remained constant from 2001 to 2011 (p=0.27). Among transfused neonates, 60% were <32 weeks' gestation (n=3210, 331/1000 births), 40% were ≥32 weeks' gestation (n= 2116, 2/1000 births) and 7% received transfusions in a hospital without a neonatal intensive care unit (NICU). Factors other than prematurity associated with higher transfusion rates were prior in utero transfusion (631/1000), congenital anomaly requiring surgery (440/1000) and haemolytic disorder (106/1000). CONCLUSIONS: In this population-based study, preterm neonates had a higher rate of transfusion than term neonates; however, 40% of those who received a transfusion were born ≥32 weeks' gestation and 7% were transfused in hospitals without an NICU. These findings need to be considered by transfusion services and personnel developing neonatal transfusion guidelines.

Blood transfusion during pregnancy, birth, and the postnatal period.

OBJECTIVES: To identify risk factors for transfusion and trends in transfusion rates across pregnancy and the postnatal period. METHODS: Linked hospital and birth data on all births in hospitals in New South Wales, Australia, between 2001 and 2010 were used to identify blood transfusions for women during pregnancy, at birth, and in the 6 weeks postpartum. Poisson regression was used to identify risk factors for red cell transfusion in the birth admission. Separate models were fitted for cesarean and vaginal births. RESULTS: Between 2001 and 2010, there were 12,147 transfusions across 891,914 pregnancies, with a transfusion rate of 1.4%. The transfusion rate increased steadily from 1.2% in 2001 to 1.6% in 2010. The majority of transfusions (91%) occurred during the birth admission, and 81% of these transfusions were associated with a diagnosis of hemorrhage. Women with bleeding or platelet disorders (vaginal: number transfused 529, relative risk [RR] 7.8, 99% confidence interval [CI] 6.9-8.7, cesarean: n=592, RR 8.7, CI 7.7-9.7) and placenta previa: (vaginal n=73, RR 4.6, CI 3.4-6.3, cesarean: n=875, RR 5.7, CI 5.1-6.4) were at highest risk of transfusion. Among vaginal births, increased risk was evident for forceps (n=1,036, RR 2.8, CI 2.5-3.0) or vacuum births (n=1,073, RR 1.9, CI 1.7-2.0) compared with nonoperative births. CONCLUSIONS: Rates of obstetric blood product transfusion have increased by 33% since 2001, with the majority of this associated with hemorrhage. Women with bleeding or platelet disorders and placenta previa are at increased risk of transfusion and should be treated accordingly. LEVEL OF EVIDENCE: II.

The three-pillar matrix of patient blood management--an overview.

Allogeneic blood transfusion has had a central role in the development and practice of numerous medical and surgical advances. In recent years, transfusion has no longer been regarded as essential for the management of a wide range of diseases and most uncomplicated elective surgeries in well-prepared patients should now be conducted without the use of transfusions. With the exception of chronic haematopoietic deficiencies, the 'transplantation' of allogeneic blood is usually supportive therapy and is generally only required in relationship to complicated major surgery, trauma and until the basic disease processes can be corrected. For most patients it is possible to minimise or avoid blood transfusion by a 'standard of care' management of a patient's own blood by optimising and preserving haematopoietic reserves in conjunction with tolerating the effects of deficiencies. The corollary to avoiding blood transfusion is that potential transfusion hazards need not be considered. This article focusses on the three-pillar matrix of patient blood management. The understanding of basic physiology and pathophysiology is at the core of evidence-based approaches to optimising erythropoiesis, minimising bleeding and tolerating anaemia.

Use of recombinant activated factor VII in Jehovah's Witness patients with critical bleeding.

INTRODUCTION: The Australian and New Zealand Haemostasis Registry (ANZHR) included patients who received off-licence recombinant activated factor VII (rFVIIa) for critical bleeding from 2000 to 2009. Approximately 1.3% of the ANZHR patients were Jehovah's Witnesses (JWs). We compared them with the non-JW patients in the registry. METHODS: Patient characteristics (e.g. gender, context of bleeding), factors influencing rFVIIa use (e.g. body temperature and pH) and outcomes (e.g. bleeding response (stopped/attenuated or unchanged) to rFVIIa, mortality) were compared between JW and non-JW patients using Fisher's exact chi-square tests and Kruskal-Wallis tests. RESULTS: A total of 42 JW and 3134 non-JW patients were included in the analysis. Approximately 99% (n = 3098) of non-JWs received blood products compared with only 30% (n = 13) of JWs (P < 0.01). The distribution of gender and contexts of critical bleeding in the two groups was significantly different. Approximately 17% of the non-JW patients were hypothermic (T < 35°C) and about 19% were acidotic (pH < 7.2) at the time of initial rFVIIa administration. Conversely, none of the JWs were hypothermic and only one was acidotic. The proportion of positive responders to rFVIIa (stopped/attenuated bleeding following rFVIIa use) was similar in both groups (75% non-JWs, 74% JWs; P = 1.0). Approximately 28% of non-JW and 17% of JW patients were deceased by day 28 following rFVIIa use (P = 0.16). DISCUSSION: Several factors were observed to be significantly different between JW and non-JW patients, yet the proportions of responders to rFVIIa were similar in both groups. The actual factors influencing response to rFVIIa are yet to be determined.

Adverse blood transfusion outcomes: establishing causation.

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.