Executive Summary Checklist

Errors in the use of blood products are a significant cause of hospital patient morbidity and mortality.  To eliminate these errors, we must implement an effective Patient Blood Management program, including the following actionable steps \cite{Meybohm_2017}:

The Performance Gap

Anemia

The healthy human body contains approximately 5-liters of blood and about 40 to 45% of blood consists of red blood cells (RBCs). Impaired blood formation, blood loss or destruction leads to anemia which represents the most common blood disorder worldwide.
About 30% of the world’s population is anemic, in other words, 1 out of every 3 people are anemic \cite{24297872}. The underlying causes can be of various etiologies; however, 30% can be attributed to malnutrition. For example, iron-deficiency is the most prominent cause due to a chronic blood loss and low iron consumption.1 Although considered a silent disease, anemia has a list of typical symptoms such as weakness, fatigue and difficulty in concentration to name a few, resulting in reduced quality of life and productivity. Due to the natural occurrence of these symptoms in our daily life the presence of anemia is often overlooked, underdiagnosed, ignored and undertreated especially in women of childbearing years (approximately ½ a billion women) \cite{23210492}. This frequently underestimated health problem is present in both the industrialized world as well as in developing countries and represents 68.3 million years lived with disability (YLD) and consumes 8.8% of all ailments worldwide \cite{18498676}.
In clinical practice hemoglobin (Hb) levels are used to determine anemia. The World Health Organization (WHO) defines a normal Hb level of ≥13 g/dL for men and ≥12 g/dL for menstruating women. Recent studies reveal the severe impact of anemia on surgical outcomes implicating anemia as a serious health condition and an independent risk factor for patients. Musallam et al., conducted a retrospective trial comprising 227,425 patients undergoing any kind of non-cardiac surgery. Non-anemic patients showed a 30-day mortality rate of 0.78% (over 158,000 patients)\cite{21982521}. In contrast, the presence of any anemia whether mild (Hb level of 10-13 g/dL in men and 10-12 g/dL in women) amplified patient’s mortality by a factor of 4.5 (3.52% in over 57,000 patients). Moreover, when patients were severely anemic (Hb level below 10 g/dL) 30-day mortality rate increased by factor 13 (more than 11,000 patients). Baron and coworkers analyzed medical reports of more than 39,000 patients confirming the association between the presence of mild anemia (Hb level of 10-13g/dL in men and 10-12g/dL in women) and increased mortality (+20% in multivariate models), longer duration of hospitalization and more frequent admission to intensive care \cite{baron2014european}. Longer hospital stays are associated with increased cost and patients are at an increased risk for other healthcare-associated conditions like falls and healthcare-associated infections (HAIs).
Being a worldwide epidemic with significant consequences addressed above, anemia requires prompt evaluation and treatment.1 Approximately 234 million surgeries are performed worldwide and about 70.2 million patients are anemic prior to surgery displaying additional (avoidable) risk factors \cite{18582931}. Of this patient population, over 21 million patients possess iron-deficiency and iron deficiency anemia that can be reverted by iron replacement \cite{Shander_2014,Whitlock_2015}. In addition, postoperative iron-deficiency anemia has an even higher prevalence, affecting up to 32 million patients.
Another emerging concept is Hospital-acquired (Associated) Anemia (HAA). Data from 10 Cleveland Clinic Hospitals revealed that 3 out of four patients admitted to their hospitals were anemic. Since this was a multi-hospital study, it is easily generalizable suggesting the high prevalence of this condition in hospitalized patients.\cite{Koch_2013} Discharge data suggest little to no appropriate therapy for this condition except for red cell (RBC) transfusion.
Moreover, a presence of anemia on admission will be made worse with ongoing blood loss dome from surgery but most from phlebotomy for redundant and unneeded tests. More than 25 million liters of phlebotomy blood a year are discarded in sewers which are 4 times the amount we transfuse \cite{Levi_2014}.
One of the if not the highest risk of anemia in hospitalized patients is the current default treatment, transfusion of RBCs. Transfusions have been demonstrated to be an independent risk factor for both morbidity and mortality and as a treatment of anemia compound the risks \cite{Isbister_2011}. Whitlock et al. analyzed in a retrospective study with 1,583,819 patients (41,421 transfused) the association of RBC transfusion and stroke and myocardial infarction. Transfusion of a single unit of RBC already increased the risk of perioperative ischemic stroke or myocardial infarction by 2.3 fold (Whitlock 2015).

Transfusions

RBC transfusions are administered to patients during active bleeding, chronic blood loss or poor production in order to increase the body’s oxygen carrying capacity. Despite the perceived benefit, many RBC transfusions have been deemed unnecessary resulting in risk or harm and defined as “overuse”. Overuse in healthcare has been defined by the Institute of Medicine (IOM) as use “in circumstances where the likelihood of benefit is negligible or zero, and therefore the patient is exposed to the risk of harm”. In general, health care providers, as well as health policy makers, are largely unaware of the significant impact that overuse in this area has on quality and safety of patients, or the cost and resource savings that can be realized by actively addressing RBC overuse. 
RBC transfusion is one of the most frequent procedures performed in U.S. hospitals and Europe, with one in ten in-patients receiving one or more blood units \cite{healthcare2009hcup}. RBC transfusion practices are highly variable by institution, procedure, and physician \cite{22531332}. Meta-analysis of risk-adjusted observational studies has shown that RBC transfusions are associated with a 69% increase in mortality and 88% increase in morbidity \cite{18496365}. Restrictive transfusion practices, in which RBC transfusions are given at lower-than-usual hemoglobin threshold, have been proven safe in multiple randomized controlled trials \cite{22513904}. These studies done repeatedly, ignore the etiology and other available modalities to effectively treat or even cure anemia. (Friedman 2012)
In response to this unmet medical need, the concept of Patient Blood Management evolved to effectively address anemia, coagulation abnormalities and assert blood conservation for all and has now shown to reduce or eliminate transfusions when applied as a multimodality approach with reduced resource utilization and improved patient outcome \cite{Goodnough_2012,world2010availability}.
The costs of RBC transfusion are not widely appreciated. In the past, the cost was estimated and ignored as part of “doing business”. In 2010, Activity Based Costing (ABC) employed in one study revealed the cost of transfusion to be between $522 and $1,183 per unit (depending on geographic location) – the study did not account for any morbid or mortality costs \cite{Shander_2010}. New infectious agents, such as the Zika virus, have also added to the ongoing risk of allogeneic transfusions, ultimately contributing to the to significant cost of this therapy \cite{Goodnough_2017}. Beyond the cost of transfusion, each RBC unit transfused is associated with increased cost of care. For example, transfusions that occur at higher hemoglobin levels increase the cost of care more than those given at lower hemoglobin levels \cite{Murphy_2007}. As mentioned above, many transfusions are unnecessary and therefore should be avoided.  A systematic, expert review of 494 studies for positive impact on health outcome showed that 59% of RBC transfusions are "inappropriate" resulting in harm to patients (Ibister 2011). Given the risk and cost of RBC transfusions, there is a growing recognition of the need to implement strategies to reduce transfusions. The Joint Commission has introduced Patient Blood Management Performance Measures that help evaluate the appropriateness of transfusions as a continuous quality indicator but lack any recommendation for anemia management \cite{joint2011implementation}. The American Medical Association and the Joint Commission, with Centers for Medicare and Medicaid Services participation, recently identified RBC transfusions as one of the top five overused procedures in medicine \cite{22667055}.
Hospitals and physicians have continued to face challenges in adopting evidence-based practice guidelines for RBC transfusions. In spite of the strong need to reduce RBC transfusions, existing tools for transfusion decision making may be lacking and this paucity may contribute to inappropriate transfusions. For example, estimated blood loss during surgery is often greater than actual blood loss, leading to incorrect assessments about the need for RBC transfusion and resulting in ‘over-transfusions’\cite{hill2011accuracy}. In addition, laboratory hemoglobin values, which are used as a primary indicator for RBC transfusions, are only available intermittently and are often delayed – leading to transfusion decisions without a laboratory hemoglobin value.(Frank 2012) In addition, repeated phlebotomies for laboratory tests are associated with induction and/or aggravation of anemia resulting in RBC transfusions in hospitalized patients \cite{24138554,21824940}. Technology to augment laboratory hemoglobin measurements, such as noninvasive and continuous hemoglobin monitoring, may provide clinicians with additional real-time trending information to determine if hemoglobin values are rising, falling, or remain stable, which may permit clinicians to make more informed and early RBC transfusion decisions.
It is estimated that the use of process changes and technology to reduce RBC transfusions can save the U.S. healthcare system in excess of five billion dollars per year, while significantly improving quality and safety \cite{at27}. Closing the performance gap will require hospitals and healthcare systems to commit to actions that will result in better healthcare outcomes with efficient use of healthcare resources. In the so far largest multicentre trial (almost 130,000 patients) in the world, it has been shown that the implementation of PBM reduces significantly the amount of transfused blood, costs and kidney damage. Overall, the implementation of PBM is safe and effective \cite{27163948}.

Leadership Plan

Based on sustained success of Patient Blood Management programs in USA, Australia, Europe, and Asia, proposals to implement change are listed below:\cite{27317382,27001367,20667328,23927725,24931841,24393629,24410741}