Transfusion strategy trials excluding patients transfused outside the trial study period are more likely to report a trend favoring restrictive strategies: a meta-analysis.

OBJECTIVES: Some large, randomized trials investigating red cell transfusion strategies have significant numbers of transfusions administered outside the trial study period. We sought to investigate the potential impact of this methodological issue. STUDY DESIGN AND SETTING: Meta-analysis of randomized controlled trials (RCTs) comparing liberal vs restrictive transfusion strategies in cardiac surgery and acute myocardial infarction patients. The outcome of interest was 30-day or in-hospital mortality. RESULTS: In cardiac surgery, the pooled risk ratio for mortality was 0.83 (95% confidence interval [CI] 0.62-1.12, P = .22) times lower in the restrictive group when compared to the liberal group in trials applying a transfusion strategy throughout the patient's entire perioperative period, and 1.33 (95% CI 0.84-2.11, P = .22) times higher in the restrictive group in trials not applying transfusion strategies throughout the entire perioperative period. When combined, the risk ratio for mortality was 0.98 (95% CI 0.73-1.32, P = .89). In patients with acute myocardial infarction, the risk ratio for mortality was 0.72 (95% CI 0.40-1.28, P = .26) times lower in the restrictive group when compared to the liberal group in 1 trial excluding patients administered the intervention prerandomization and 1.19 (95% CI 0.96-1.47, P = .11) times higher in the restrictive group in 1 trial including patients receiving the intervention prerandomization. When combined the risk ratio for mortality was 1.00 (0.62-1.59, P = .99). CONCLUSION: Though not statistically significant, there was a consistent difference in trends between RCTs administering significant numbers of transfusion outside the trial study period compared to those that did not. The implications of our results may extend to RCTs in other settings that ignore if and how frequently an investigated therapy is administered outside the trial window.

Data and Metrics for Patient Blood Management: A Narrative Review and Practical Guide.

Data collection, analysis, and reporting are fundamental for a successful hospital-based patient blood management program; however, very little has been published on the topic. Our aim was to synthesize evidence from a literature review to provide a detailed, practical list of outcome metrics, and the required data collection(s) to inform implementation. Ovid MEDLINE and PubMed were searched for any full-text original research articles published from inception to the year 2020. We included any studies reporting the implementation of interventions or programs study authors defined as "patient blood management" and extracted information on data collected and metrics reported. We included 45 studies describing the implementation of a patient blood management program and/or strategies. The outcomes reported by these studies were grouped into 1 of 36 metrics. We compiled a list of 65 relevant data elements to collect, and their potential source hospital information systems: patient administration, laboratory, transfusion/blood bank, operating room, pharmacy, emergency department, and intensive care unit. We further categorized patient blood management data systems into basic, intermediate, and advanced based on the combination of different information systems sourced. The results of this review can be used to inform patient blood management programs in planning what data collection(s) are needed, where these data can be sourced from, and how they can be analyzed.

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.

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.

Special Report From the Society for the Advancement of Blood Management: The Choosing Wisely Campaign.

Over 7 years ago, the American Board of Internal Medicine Foundation (ABIM) created the national Choosing Wisely campaign with the purpose of encouraging active dialogue between health care providers and patients, focusing on appropriateness, quality care, and resource management. This special communication from the Society for the Advancement of Blood Management (SABM) serves to highlight the society's recent participation in the Choosing Wisely campaign, encouraging sensible dialogue between clinicians and our patients with the intent to promote patient-centered, evidence-based care. The article addresses the rationale and supportive data for the 5 SABM Choosing Wisely recommendations.

Reducing red blood cell transfusion in orthopedic and cardiac surgeries with Antifibrinolytics: A laboratory medicine best practice systematic review and meta-analysis.

OBJECTIVES: To evaluate the effectiveness of antifibrinolytics tranexamic acid (TA), ε-aminocaproic acid (EACA), and aprotinin to decrease overuse of red blood cell transfusions in adult surgical and non-surgical patients. METHODS: This review followed the Centers for Disease Control and Prevention (CDC) Laboratory Medicine Best Practice (LMBP™) Systematic Review (A-6) method. Eligible studies were assessed for evidence of effectiveness of TA or EACA in reducing the number of patients transfused or the number of whole blood transfusions. RESULTS: Seventy-two articles met LMBP™ inclusion criteria. Fifty-six studies assessed Topical, Intra-articular Injection, or Intravenous TA, 4 studied EACA, and 12 studied the effectiveness of aprotinin. The overall strength of the body of evidence of effectiveness for each of these practices was rated as high. CONCLUSION: LMBP™ recommends the use of topical, intra-articular injection, or intravenous tranexamic acid and the use of ε-aminocaproic acid for reducing overuse of red blood cell transfusion.

Restrictive Transfusion Strategy and Clinical Decision Support Practices for Reducing RBC Transfusion Overuse.

OBJECTIVES: Assess support for the effectiveness of two separate practices, restrictive transfusion strategy and computerized physician order entry/clinical decision support (CPOE/CDS) tools, in decreasing RBC transfusions in adult surgical and nonsurgical patients. METHODS: Following the Centers for Disease Control and Prevention Laboratory Medicine Best Practice (LMBP) Systematic Review (A-6) method, studies were assessed for quality and evidence of effectiveness in reducing the percentage of patients transfused and/or units of blood transfused. RESULTS: Twenty-five studies on restrictive transfusion practice and seven studies on CPOE/CDS practice met LMBP inclusion criteria. The overall strength of the body of evidence of effectiveness for restrictive transfusion strategy and CPOE/CDS was rated as high. CONCLUSIONS: Based on these procedures, adherence to an institutional restrictive transfusion strategy and use of CPOE/CDS tools for hemoglobin alerts or reminders of the institution's restrictive transfusion policies are effective in reducing RBC transfusion overuse.

Society for the advancement of blood management administrative and clinical standards for patient blood management programs. 4th edition (pediatric version).

Patient Blood Management is the timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize hemostasis, and minimize blood loss to improve patient outcomes. Conceptually similar to a "bundle" strategy, it is designed to improve clinical care using comprehensive evidence-based treatment strategies to manage patients with potential or ongoing critical bleeding, bleeding diathesis, critical anemia, and/ or a coagulopathy. Patient Blood Management includes multimodal strategies to screen, diagnose and properly treat anemia, coagulopathies and minimize bleeding, using goal-directed therapy and leverages a patient's physiologic ability to adapt to anemia while definitive treatment is undertaken. Allogeneic blood component transfusion is one traditional therapeutic modality out of many for managing blood loss and anemia and, while it may be the best choice in certain situations, other effective and more appropriate options are available and should be used in conjunction or alone. Therefore, comprehensive Patient Blood Management is the new standard of care to prevent and manage anemia and optimize hemostasis and has been recommended by the World Health Organization, the American Society of Anesthesiologists, the European Society of Anaesthesiology and the Australian National Blood Authority. While there is a plethora of expert consensus and good practice guidelines published for blood component transfusion from multiple professional organizations and societies, there remains a need for more comprehensive and broader standards of patient medical management to proactively reduce the risk of exposure to allogeneic transfusions. In 2010, the Society for Advancement of Blood Management published the first comprehensive standards to address the administrative and clinical components of an effective, patient-centered Patient Blood Management program. Recognizing the need to reduce inappropriate transfusions, some professional organizations have placed their emphasis on transfusion guidelines. In contrast, the focus of the Society for Advancement of Blood Management Standard is on the centrality of the patient and the full spectrum of therapeutic strategies needed to improve clinical outcomes in patients at risk for blood loss or anemia, thereby reducing avoidable transfusions as well. The Standards are meant not to replace, but to complement transfusion guidelines by more completely addressing the need for a multi-modal clinical approach with the goal to improve patient outcomes. Compared to adult programs, Pediatric Patient Blood Management programs are currently not commonly accepted as standard of care for pediatric patients. This is partly due to the fact that, until recently, there was a paucity of robust evidence-based literature and expert consensus guidelines on pediatric PBM. Managing pediatric bleeding and blood product transfusion presents a unique set of challenges. The main goal of transfusion is to correct or avoid imminent inadequate oxygen carrying capacity caused by inadequate red blood cell mass. Determining when, what, and how much to transfuse can be difficult. Neonates, infants, children, and adolescents each have specific considerations based on age, weight, physiology, and pharmacology. In this edition of Pediatric Anaesthesia we provide, in abbreviated format, the 4th edition of the Administrative and Clinical Standards for Patient Blood Management; Pediatric Version, first published in 2010 with the addition of a new Pediatric section in 2016. These Standards provide guidance for implementing a comprehensive Pediatric Patient Blood Management program at both pediatric and adult medical institutions. While every hospital may not be equipped to have a dedicated Pediatric Patient Blood Management program, this document highlights important universal clinical strategies that can be implemented to optimize pediatric bleeding management and minimize allogeneic blood product exposure through the use of multi-modal therapeutic strategies that have their central emphasis on the patient rather than the transfusion. Important strategies include: treatment of preoperative anemia, standardized transfusion algorithms, the use of restrictive transfusion thresholds, goal-directed therapy based on point of care and viscoelastic testing, antifibrinolytics, and avoidance of hemodilution and hypothermia as supported by evidence. For the full version, please go to https://www.sabm.org/publications.

Anemia Management and Audit Feedback Practices for Reducing Overuse of RBC Transfusion: A Laboratory Medicine Best Practice Systematic Review and Meta-Analysis.

Objectives: To evaluate the effectiveness of anemia management and audit with feedback practices in reducing overuse of RBC transfusion. Methods: This review follows the Centers for Disease Control and Prevention's Laboratory Medicine Best Practice Systematic Review (A-6) method. We searched the literature and solicited unpublished studies on practices to reduce overuse of RBC transfusions as measured by reductions in units transfused and proportion of patients transfused. Results: Thirteen studies on preoperative anemia management and three studies on audit feedback practices met inclusion criteria. Strength of evidence was high to moderate for reducing the number of units and proportion of patients transfused. Conclusions: Preoperative anemia management reduces the proportion of patients transfused and units of RBCs transfused. Audit with feedback across cases, physicians, and/or service areas, as part of a continuous quality improvement practice, reduces the proportion of patients and units of RBCs transfused.

Management of anemia in patients with congestive heart failure.

Anemia is an independent risk factor for adverse patient outcomes. There are no guidelines for management of anemia in patients with congestive heart failure (CHF), despite its high incidence. Four objectives were defined by the International Anemia Management and Clinical Outcomes Expert Panel (AMCO), a multinational group of interdisciplinary experts identified by the Society for the Advancement of Blood Management (SABM) to: determine the prevalence of anemia in outpatients; to determine the prevalence of hospital-acquired anemia; to assess the impact of anemia management on clinical outcomes such as quality of life and functional status; and to provide recommendations for primary care physicians and specialists for the diagnosis, evaluation, and management of anemia in patients with CHF. Anemia and iron deficiency were confirmed to be highly prevalent in patients with CHF. Intravenous iron therapy improves anemia, cardiac function and exercise tolerance, leading to improvement in quality of life. Anemia management has been demonstrated to be cost-effective. Clinical care pathways to manage anemia in patients with CHF are recommended as best practices in order to improve patient outcomes. Am. J. Hematol. 92:88-93, 2017. © 2016 Wiley Periodicals, Inc.

Observational studies - should we simply ignore them in assessing transfusion outcomes?

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. 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.

Impact of a Patient Blood Management Program and an Outpatient Anemia Management Protocol on Red Cell Transfusions in Oncology Inpatients and Outpatients.

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.

Effects of tranexamic acid and bipolar sealer alone or in combination in primary total knee arthroplasty: a prospective, randomized, controlled trial.

BACKGROUND: The purpose of this study was to compare 2 blood management interventions, tranexamic acid (TXA) and bipolar sealer system (BSS) used independently or in combination with a control group during primary total knee arthroplasty (TKA). METHODS: A total of 127 TKA patients were enrolled and randomized into 4 groups: Intravenous TXA plus the BSS (N = 29, group 1); TXA only (N = 29, group 2); BSS only (N = 31, group 3); and intravenous normal saline as a control group (N = 32, group 4). RESULTS: Changes in hemoglobin from baseline to postoperative follow-up were significantly lower among patients who received TXA plus BSS and those receiving TXA only when compared with the control. BSS only did not differ significantly when compared to the control group. In addition, TXA plus BSS was as efficacious as TXA only in preserving postoperative hemoglobin. CONCLUSIONS: In other terms, using bipolar sealer did not add to the effect of TXA in reducing the postoperative hemoglobin drop in primary TKA.

Patient blood management in cardiac surgery results in fewer transfusions and better outcome.

BACKGROUND: The aim of this study was to investigate the impact of the introduction of a patient blood management (PBM) program in cardiac surgery on transfusion incidence and outcome. STUDY DESIGN AND METHODS: Clinical and transfusion data were compared between the pre-PBM epoch (July 2006-March 2007) and the PBM epoch (April 2007-September 2012). RESULTS: There were a total of 2662 patients analyzed, 387 in the pre-PBM and 2275 in the PBM epoch. Red blood cell (RBC) loss decreased from a mean (±SD) of 810 ± 426 mL (median, 721 mL) to 605 ± 369 mL (median, 552 mL; p < 0.001) and pretransfusion hemoglobin decreased from 7.2 ± 1.4 to 6.6 ± 1.2 g/dL (p < 0.001) in the pre-PBM versus the PBM epoch. In conjunction, this resulted in a reduction of the RBC transfusion rate from 39.3% to 20.8% (p < 0.001). Similar reductions were observed for the transfusion of fresh-frozen plasma (FFP; from 18.3% to 6.5%, p < 0.001) and platelets (PLTs; from 17.8% to 9.8%, p < 0.001). Hospital mortality and cerebral vascular accident incidence remained unchanged in the PBM epoch. However, the incidence of postoperative kidney injury decreased in the PMB epoch (from 7.6% to 5.0%, p = 0.039), length of hospital stay decreased from 12.2 ± 9.6 days (median, 10 days) to 10.4 ± 8.0 days (median, 8 days; p < 0.001), and total adjusted direct costs were reduced from $48,375 ± $28,053 (median, $39,709) to $44,300 ± $25,915 (median, $36,906; p < 0.001). CONCLUSIONS: Implementing meticulous surgical technique, a goal-directed coagulation algorithm, and a more restrictive transfusion threshold in combination resulted in a substantial decrease in RBC, FFP, and PLT transfusions; less kidney injury; a shorter length of hospital stay; and lower total direct costs.