Blood transfusion is one of the most common hospital procedures in developed countries. However, inappropriate use of blood transfusion is common, and this is of considerable concern because transfusion is known to be associated with adverse events and is costly. Reductions in blood use have resulted from recent evidence indicating that restrictive use of red blood cell transfusions is associated with similar patient outcomes to liberal strategies and from a focus on patient blood management (PBM), which recognizes the importance of conserving the patient’s own blood alongside the judicious use of transfusion. A recent Consensus Conference in Frankfurt developed practice and research recommendations for PBM but also indicated that additional studies are needed to provide better evidence for PBM interventions, including for improved patient outcomes and lower hospital costs as well as for reductions in blood utilization. In the meanwhile, it is of utmost importance to translate PBM guidelines into practical day-to-day recommendations and encourage their use to make PBM “the standard of care.”

Learning Objectives

  • Recognize that there is considerable potential to improve the management of patients at risk of transfusion

  • Understand that the key issue is to improve the management of anemia

  • Propose that the implementation of patient blood management measures should be the standard of care

A 64-year-old female is referred to the Department of Orthopedic Surgery with chronic infection of a hip replacement that requires revision surgery. The patient is otherwise fit and well but has a history of myocardial infarction 3 years ago.

A full blood count is performed as soon as the patient is listed for surgery, maximizing the available time for preoptimization. Hemoglobin (Hb) concentration is 9.8 g/dL, and therefore hematinics are measured. These reveal a transferrin saturation of 9% (normal, 16%-50%), ferritin of 475 μg/L (normal, 12-150 μg/L), and C-reactive protein of 34 mg/L (normal, <10 mg/L). These results are compatible with a diagnosis of functional iron deficiency. Vitamin B12 and folate levels are within normal range, and a referral is made to gastroenterology to exclude gastrointestinal malignancy.

An IV iron infusion of 1 g ferric carboxymaltose is administered 6 weeks before surgery, which increases the Hb to 10.8 g/dL by the day of surgery.

Pretransfusion compatibility testing reveals multiple red blood cell (RBC) antibodies. It is not possible to accurately estimate the number of donor blood units that will be required for surgery; however, blood loss >1 L is anticipated. Four compatible RBC units are identified and transported to the blood bank in advance of surgery.

Surgery is performed under spinal anesthesia; 1 g IV tranexamic acid is administered at the start of the procedure, and 1 g is administered topically to the surgical field at the end of the procedure. Intraoperative cell salvage produces 256 mL (hematocrit 60%) that are reinfused during the procedure. No drains are used postoperatively.

During the postoperative period, the Hb is 7.7 g/dL, and a single unit of donor RBCs is transfused. The Hb transfusion threshold was 8.0 g/dL, in line with the findings of the Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS) trial,1  which found that a liberal RBC transfusion policy (Hb transfusion threshold of 10.0 g/dL) did not reduce rates of death, inability to walk independently on 60-day follow-up, or in-hospital morbidity in elderly patients at high cardiovascular risk in comparison with a restrictive policy (Hb transfusion threshold of 8.0 g/dL). The Hb increased to 8.8 g/dL. The decision to transfuse donor blood is guided by an electronic decision support tool within the electronic patient record. No additional donor blood is required.

Blood transfusion is one of the most common hospital procedures in developed countries, such as the United States and the United Kingdom.2  Over 11.3 million units of RBCs, 1.9 million units of platelets, and 2.7 million units of plasma were transfused to patients in the United States in 2015,3  and there were nearly 3 million blood donations in the United Kingdom in 2017.4  Unnecessary use of blood transfusion is common worldwide; national audits of blood transfusion in England and elsewhere suggest that there is substantial inappropriate use of transfusions of all types of blood components.5,6  Recent evidence indicates that strategies for the restrictive use of RBC transfusions reduce transfusions but are associated with similar patient outcomes to liberal transfusion strategies.1,7-11  A systematic review of 31 randomized, controlled trials involving >12 000 patients found that transfusing at an Hb concentration between 7 and 8 g/dL decreased the proportion of participants exposed to RBC transfusion by 43% across a broad range of clinical specialties, but there was no difference in mortality or morbidity, such as cardiac events, stroke, pneumonia, thromboembolism, or infection, compared with a liberal transfusion strategy (pretransfusion Hb, 9-10 g/dL).10  These data from randomized, controlled trials are of considerable importance, because they repudiate data from retrospective and observational studies indicating a variety of adverse outcomes associated with transfusion.12  However, transfusions are costly, and they are well known to be associated with adverse events. The inclusion of the evidence for restrictive RBC transfusion in practice guidelines for transfusion13,14  has resulted in a worldwide reduction in the use of RBC transfusions; some hospitals are using strategies, such as electronic decision support, to support the implementation of restrictive RBC transfusion.15  In recent years, there has also been a focus on patient blood management (PBM), which recognizes the importance of conserving the patient’s own blood alongside the judicious use of transfusion. PBM is relevant to each stage of the patient journey (see the case study above).

An early driver of exploring measures for blood conservation and the avoidance of blood transfusion was the need to provide modern medical and surgical care for those individuals objecting to transfusion because of their religious beliefs.15  Additional interest derived from other events, such as the recognition of transfusion-transmitted hepatitis C virus and HIV, concerns about the transmission by transfusion of variant Creutzfeldt–Jakob disease particularly in the United Kingdom, and evidence for the safety of restrictive transfusion practice beginning with the Transfusion Requirements in Critical Care trial published in 1999.7  These efforts became organized through the formation of bodies, such as the National Association of Bloodless Medicine and Surgery (1996), The Network for the Advancement of Transfusion Alternatives (1998; now the Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis), and the Society for the Advancement of Blood Management (2000).

The World Health Organization defines PBM as “a patient-focused, evidence-based and systematic approach to optimize the management of patients and transfusion of blood products for quality and effective patient care. It is designed to improve patient outcomes through the safe and rationale use of blood and blood products and by minimizing unnecessary exposure to blood products.”16 

An alternative definition takes the focus away from transfusion and puts it on improving patient outcomes: “PBM is the timely application of evidence-based medical and surgical concepts designed to maintain Hb concentration, optimize hemostasis and minimize blood loss in an effort to improve patient outcome.”17  These are sometimes termed the “3 pillars” of PBM, and each pillar is illustrated by our case study.

Anemia is very common in hospitalized patients. The main causes are blood loss, poor RBC production, and hemolysis. A study by the American College of Surgeons National Surgical Quality Improvement Program involving 211 hospitals worldwide and 277 425 patients found that 30% of noncardiac surgery patients had anemia on admission.18  There was an increased risk of 30-day mortality and 30-day morbidity in anemic compared with nonanemic patients in both those with mild anemia and those with moderate severe anemia. Similar results have been found in other studies19,20  and a meta-analysis of 24 observational studies, which found that preoperative anemia was associated with an increased risk of adverse outcomes, including mortality.21 

A recent retrospective study of 445 371 patients who survived after hospitalization in an integrated network of 21 hospitals found that the prevalence of moderate anemia (Hb, 7-10 g/dL) at discharge from the hospital increased from 20% to 25% and that RBC transfusions decreased by 28% in the same period from 2010 to 2014. The increase in anemia at hospital discharge was not associated with a rise in rehospitalization, subsequent RBC transfusion, or mortality within 6 months of discharge.22  The authors concluded that their data supported the safety of efforts to limit RBC transfusion and tolerate anemia during and after hospitalization. In an accompanying editorial, Shander and Goodnough23  emphasized the harms caused by anemia and questioned the false choice between transfusion and tolerance of anemia. They argued that the mindset of “transfusion or anemia” risks calls for even more restrictive transfusion trials rather than focusing on the needs of the patient, which are the judicious use of transfusion, with its known risks and costs, as a short-term measure to prevent tissue hypoxia and ischemia followed by specific treatments for anemia.23 

The change in Hb concentration may be more important than absolute values. A difference in Hb of ≥50% after gastrointestinal surgery was associated with complications, especially ischemic adverse events, even if the absolute nadir level of Hb remained greater than the transfusion threshold of 70 g/L.24 

Over the last 10 years, there have been many publications indicating that PBM implemented in various ways reduces the use of transfusions, but less convincing are data on improvement in clinical outcomes as already described above.25-28 

An example of such a PBM study is the one conducted in Western Australia, which initiated a comprehensive health system–wide PBM program in 2008.27  It was a retrospective study of 605 046 patients admitted to 4 major adult tertiary care hospitals between July 2008 and June 2014. Comparing final year with baseline, units of RBCs, fresh frozen plasma, and platelets transfused per admission decreased by 41%, representing a saving of over US$18 million. Mean pretransfusion Hb decreased from 7.9 to 7.3 g/dL, and the proportion of elective surgery admissions admitted anemic decreased from 20.8% to 14.4%. Single-unit RBC transfusions increased from 33.3% to 63.7%. There were risk-adjusted reductions in hospital mortality (odds ratio [OR], 0.72; 95% confidence interval [95% CI], 0.67-0.77; P < .001), length of stay (incidence rate ratio, 0.85; 95% CI, 0.84-0.87; P < .001), hospital-acquired infections (OR, 0.79; 95% CI, 0.73-0.86; P < .001), and acute myocardial infarction/stroke (OR, 0.69; 95% CI, 0.58-0.82; P < .001).

Several national bodies and international groups of experts have produced recommendations for PBM.29-33  The most ambitious of these initiatives was the Consensus Conference held in Frankfurt in April 2018.34 

The Consensus Conference was held in Frankfurt in April 2018, and it was based on a considerable amount of preparatory work in conducting systematic reviews before the conference and the presentations and discussion at the conference focusing on 17 population/intervention/comparison/outcome (PICO) questions on RBC transfusion in adult patients (Table 1). The questions encompassed preoperative anemia (3 questions), RBC transfusion thresholds (11 questions), and implementation of PBM programs (3 questions). MEDLINE, EMBASE, Cochrane Library, and the Transfusion Evidence Library were searched for relevant literature through January 2018. Meta-analyses were conducted by 3 panels, including clinical and scientific experts, nurses, patient representatives, and methodologists using the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) methodology35  and the Evidence-to-Decision framework,36  to develop clinical recommendations.

Table 1.

The 17 Frankfurt Consensus Conference on PBM (2018)34  PICO questions

PICO questions
Preoperative anemia 
 PICO 1: Adverse events. In elective surgery patients [population], is preoperative anemia [intervention/risk factor] a risk factor for adverse clinical or economic outcome [outcomes] compared with no preoperative anemia [comparison]? 
 PICO 2: Definition. In elective surgery patients [population], should a specific Hb cutoff [index test] vs another Hb cutoff [comparator test] be used to diagnose preoperative anemia [outcome]? (It was not answered because of lack in evidence) 
 PICO 3: Management. In elective surgery patients with preoperative anemia [population], is the use of RBC transfusion or iron supplementation and/or erythrocyte-stimulating agents [intervention] effective to improve clinical and economic outcomes [outcomes] compared with no intervention/placebo/standard of care [comparison]? 
RBC concentrate transfusion thresholds 
 PICO 4: Adult intensive care patients. In critically ill but clinically stable adult intensive care patients [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 5: Orthopedic and noncardiac surgery. In elderly high-risk (cardiovascular) patients undergoing orthopedic or noncardiac surgery [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 6: Acute gastrointestinal bleeding. In patients with an acute gastrointestinal bleeding [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 7: Coronary heart disease. In patients with symptomatic coronary heart disease [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 8: Septic shock. In patients with septic shock [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 9: Cardiac surgery. In patients undergoing cardiac surgery [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 10: Adult hematological patients. In adult hematological patients [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 11: Adult patients with solid tumors. In adult patients with solid tumors [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 12: Acute central nervous system injury. In patients with acute central nervous system injury [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 13: Cerebral perfusion disorders. In patients with cerebral perfusion disorders [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 14: Acute bleeding. In patients with acute bleeding [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
Implementation of PBM programs 
 PICO 15: Effectiveness of PBM implementation. Is a PBM program [intervention] effective to improve clinical and economic outcomes [outcomes] compared with no PBM program [comparison]? 
 PICO 16: PBM promotional tools: behavioral interventions. Is a specific behavioral intervention to promote the implementation of a PBM program [intervention] more effective to improve clinical and economic outcomes [outcomes] compared with no/another behavioral intervention [comparison]? 
 PICO 17: PBM promotional tools: decision support systems. Is a specific decision support system to promote the implementation of a PBM program [intervention] more effective to improve clinical and economic outcomes [outcomes] compared with no intervention or another decision support system/behavioral intervention [comparison]? 
PICO questions
Preoperative anemia 
 PICO 1: Adverse events. In elective surgery patients [population], is preoperative anemia [intervention/risk factor] a risk factor for adverse clinical or economic outcome [outcomes] compared with no preoperative anemia [comparison]? 
 PICO 2: Definition. In elective surgery patients [population], should a specific Hb cutoff [index test] vs another Hb cutoff [comparator test] be used to diagnose preoperative anemia [outcome]? (It was not answered because of lack in evidence) 
 PICO 3: Management. In elective surgery patients with preoperative anemia [population], is the use of RBC transfusion or iron supplementation and/or erythrocyte-stimulating agents [intervention] effective to improve clinical and economic outcomes [outcomes] compared with no intervention/placebo/standard of care [comparison]? 
RBC concentrate transfusion thresholds 
 PICO 4: Adult intensive care patients. In critically ill but clinically stable adult intensive care patients [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 5: Orthopedic and noncardiac surgery. In elderly high-risk (cardiovascular) patients undergoing orthopedic or noncardiac surgery [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 6: Acute gastrointestinal bleeding. In patients with an acute gastrointestinal bleeding [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 7: Coronary heart disease. In patients with symptomatic coronary heart disease [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 8: Septic shock. In patients with septic shock [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 9: Cardiac surgery. In patients undergoing cardiac surgery [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 10: Adult hematological patients. In adult hematological patients [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 11: Adult patients with solid tumors. In adult patients with solid tumors [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 12: Acute central nervous system injury. In patients with acute central nervous system injury [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 13: Cerebral perfusion disorders. In patients with cerebral perfusion disorders [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
 PICO 14: Acute bleeding. In patients with acute bleeding [population], is the use of a restrictive transfusion threshold [intervention] effective to reduce mortality and improve other clinical outcomes [outcomes] compared with a liberal transfusion threshold [comparison]? 
Implementation of PBM programs 
 PICO 15: Effectiveness of PBM implementation. Is a PBM program [intervention] effective to improve clinical and economic outcomes [outcomes] compared with no PBM program [comparison]? 
 PICO 16: PBM promotional tools: behavioral interventions. Is a specific behavioral intervention to promote the implementation of a PBM program [intervention] more effective to improve clinical and economic outcomes [outcomes] compared with no/another behavioral intervention [comparison]? 
 PICO 17: PBM promotional tools: decision support systems. Is a specific decision support system to promote the implementation of a PBM program [intervention] more effective to improve clinical and economic outcomes [outcomes] compared with no intervention or another decision support system/behavioral intervention [comparison]? 

In total, 17 607 literature citations were identified to be associated with the 17 PICO questions, including 145 studies, of which 63 were randomized clinical trials with 23 143 patients and 82 were observational studies with >4 million patients. The recommendations are shown in Table 2. For preoperative anemia, 4 clinical and 3 research recommendations were developed, including the strong recommendation to detect and manage anemia sufficiently early before major elective surgery. For RBC transfusion thresholds, 4 clinical and 6 research recommendations were developed, including 2 strong clinical recommendations for critically ill but clinically stable intensive care patients with or without septic shock (recommended threshold for RBC transfusion: Hb < 7 g/dL) as well as patients undergoing cardiac surgery (recommended threshold for RBC transfusion: Hb < 7.5 g/dL). For the implementation of PBM programs, 2 clinical and 3 research recommendations were developed, including recommendations to implement comprehensive PBM programs and use electronic decision support systems to improve appropriate RBC utilization. These recommendations should be adopted for current clinical practice (see the case study).

Table 2.

The 10 Frankfurt Consensus Conference on PBM (2018)34  clinical recommendations (CRs)

CRLevel of evidence
Preoperative anemia  
 CR 1: Detection and management of preoperative anemia early enough before major elective surgery Strong recommendation, low certainty in the evidence of effects 
 CR 2: Use of iron supplementation in adult preoperative elective surgery patients with iron-deficient anemia to reduce RBC transfusion rate Conditional recommendation, moderate certainty in the evidence of effects 
 CR 3: Do not use erythropoiesis-stimulating agents routinely in general adult preoperative elective surgery patients with anemia Conditional recommendation, low certainty in the evidence of effects 
 CR 4: Consider short-acting erythropoietins in addition to iron supplementation in adult preoperative elective major orthopedic surgery patients with Hb levels <13 g/dL to reduce transfusion rates Conditional recommendation, low certainty in the evidence of effects 
RBC transfusion thresholds  
 CR 5: Restrictive RBC transfusion threshold (Hb < 7 g/dL) in critically ill but clinically stable intensive care patients Strong recommendation, moderate certainty in the evidence of effects 
 CR 6: Restrictive RBC transfusion threshold (Hb < 7.5 g/dL) in cardiac surgery patients Strong recommendation, moderate certainty in the evidence of effects 
 CR 7: Restrictive transfusion threshold (Hb < 8 g/dL) in patients with hip fracture and cardiovascular disease or other risk factors Conditional recommendation, moderate certainty in the evidence of effects 
 CR 8: Restrictive transfusion threshold (Hb = 7-8 g/dL) in hemodynamically stable patients with acute gastrointestinal bleeding Conditional recommendation, low certainty in the evidence of effects 
Implementation of PBM programs  
 CR 9: Implementation of PBM programs to improve appropriate RBC utilization Conditional recommendation, low certainty in the evidence of effects 
 CR 10: Computerized/electronic decision support systems to improve appropriate RBC utilization Conditional recommendation, low certainty in the evidence of effects 
CRLevel of evidence
Preoperative anemia  
 CR 1: Detection and management of preoperative anemia early enough before major elective surgery Strong recommendation, low certainty in the evidence of effects 
 CR 2: Use of iron supplementation in adult preoperative elective surgery patients with iron-deficient anemia to reduce RBC transfusion rate Conditional recommendation, moderate certainty in the evidence of effects 
 CR 3: Do not use erythropoiesis-stimulating agents routinely in general adult preoperative elective surgery patients with anemia Conditional recommendation, low certainty in the evidence of effects 
 CR 4: Consider short-acting erythropoietins in addition to iron supplementation in adult preoperative elective major orthopedic surgery patients with Hb levels <13 g/dL to reduce transfusion rates Conditional recommendation, low certainty in the evidence of effects 
RBC transfusion thresholds  
 CR 5: Restrictive RBC transfusion threshold (Hb < 7 g/dL) in critically ill but clinically stable intensive care patients Strong recommendation, moderate certainty in the evidence of effects 
 CR 6: Restrictive RBC transfusion threshold (Hb < 7.5 g/dL) in cardiac surgery patients Strong recommendation, moderate certainty in the evidence of effects 
 CR 7: Restrictive transfusion threshold (Hb < 8 g/dL) in patients with hip fracture and cardiovascular disease or other risk factors Conditional recommendation, moderate certainty in the evidence of effects 
 CR 8: Restrictive transfusion threshold (Hb = 7-8 g/dL) in hemodynamically stable patients with acute gastrointestinal bleeding Conditional recommendation, low certainty in the evidence of effects 
Implementation of PBM programs  
 CR 9: Implementation of PBM programs to improve appropriate RBC utilization Conditional recommendation, low certainty in the evidence of effects 
 CR 10: Computerized/electronic decision support systems to improve appropriate RBC utilization Conditional recommendation, low certainty in the evidence of effects 

The quality of evidence for the majority of questions considered at the Consensus Conference apart from RBC transfusion thresholds was moderate to very low. This limited the number of strong recommendations for many of the key questions for PBM and supports the need for additional research and a consensus for clinically meaningful end points for multicenter trials. Research recommendations were made for priority questions in areas with limited evidence (Table 3).

Table 3.

The 12 Frankfurt Consensus Conference on PBM (2018)34  research recommendations

Research recommendations
Preoperative anemia 
 R1: Because published studies show major differences in the Hb values used for the definition of preoperative anemia, the expert panel recommends identifying optimal Hb thresholds in different patient groups as well as adequate cutoff values 
 R2: The expert panel suggests addressing the effects of iron supplementation in nonanemic but iron-deficient patients scheduled for major surgery 
 R3: The expert panel recommends investigating the use of short-acting erythropoietins plus iron supplementation in adult preoperative elective surgery patients with focus on long-term (un-)desirable effects, optimal dose, type of surgery (particularly cancer surgery), copresence of iron deficiency, and cost effectiveness 
RBC concentrate transfusion threshold 
 R4: The expert panel recommends additional research on restrictive RBC transfusion thresholds for hemodynamically stable patients with acute upper or lower gastrointestinal bleeding; the panel does not recommend additional research in hemodynamically unstable patients with acute major bleeding 
 R5-R9: The expert panel suggests additional research on RBC transfusion support in patients with hematological and oncological diseases, coronary heart diseases, noncardiac/nonorthopedic surgery, or brain injury 
 Rx (no evidence): No additional research on Hb thresholds in acutely bleeding patients 
Implementation of PBM programs 
 R10-R12: The expert panel suggests additional research on the impact of PBM programs on 
  a) adverse events and patient-important outcomes 
  b) compliance, adherence, and acceptability 
  c) cost-effectiveness 
 Reproducible definitions and outcome parameters have to be defined beforehand to evaluate the sustainability of PBM programs 
Research recommendations
Preoperative anemia 
 R1: Because published studies show major differences in the Hb values used for the definition of preoperative anemia, the expert panel recommends identifying optimal Hb thresholds in different patient groups as well as adequate cutoff values 
 R2: The expert panel suggests addressing the effects of iron supplementation in nonanemic but iron-deficient patients scheduled for major surgery 
 R3: The expert panel recommends investigating the use of short-acting erythropoietins plus iron supplementation in adult preoperative elective surgery patients with focus on long-term (un-)desirable effects, optimal dose, type of surgery (particularly cancer surgery), copresence of iron deficiency, and cost effectiveness 
RBC concentrate transfusion threshold 
 R4: The expert panel recommends additional research on restrictive RBC transfusion thresholds for hemodynamically stable patients with acute upper or lower gastrointestinal bleeding; the panel does not recommend additional research in hemodynamically unstable patients with acute major bleeding 
 R5-R9: The expert panel suggests additional research on RBC transfusion support in patients with hematological and oncological diseases, coronary heart diseases, noncardiac/nonorthopedic surgery, or brain injury 
 Rx (no evidence): No additional research on Hb thresholds in acutely bleeding patients 
Implementation of PBM programs 
 R10-R12: The expert panel suggests additional research on the impact of PBM programs on 
  a) adverse events and patient-important outcomes 
  b) compliance, adherence, and acceptability 
  c) cost-effectiveness 
 Reproducible definitions and outcome parameters have to be defined beforehand to evaluate the sustainability of PBM programs 

The vast majority of clinical PBM implementation trials were observational and only focused on the number of units of RBCs transfused rather than clinical outcomes, such as patient survival and adverse events. There was concern about bias owing to concurrent interventions or practice evolution that might have occurred during the study period in the reports of these studies as well as the lack of information about how well the PBM interventions of interest were actually implemented in practice. The assessment of reduction in “inappropriate transfusion” (ie, transfusions given outside current guidelines) was often not addressed. Health economic evaluations were lacking to provide robust data on the cost savings, which were primarily in reduced blood usage, compared with the costs of the interventions. Although there was evidence for reduction in RBC use resulting from PBM implementation, there was inadequate evidence for reduction of platelet and plasma usage.

As already indicated in this review, several national bodies and international groups of experts have produced recommendations for PBM.29-33  A different challenge is to develop “standards” for PBM to encourage the measurement of key parameters and facilitate the identification of opportunities for improvement. The Joint Commission developed performance measures for PBM in collaboration with the University of Pittsburgh (Table 4).37  The American Association of Blood Banks (AABB) followed this by developing Standards for PBM in 2014, updating them in 2018,38  and establishing PBM certification in partnership with The Joint Commission. At the time of writing, 6 centers have achieved PBM certification, and it is expected that 30 centers will have done so by the end of 2020.

Table 4.

Performance measures for PBM37 

No.Measure nameMeasureComments
PBM-01 Transfusion consent N: Patients with a signed consent who received information about the risks, benefits, and alternatives before the initial blood transfusion or the initial transfusion was deemed a medical emergency Include all patients 
D: Patients who received a transfusion of RBCs, PLTs, or plasma 
PBM-02 RBC transfusion indication N: No. of RBC units (bags) with pretransfusion Hb or Hct result and clinical indication documented Include all patients 
D: No. of transfused RBC units evaluated 
PBM-03 Plasma transfusion indication N: No. of plasma units (bags) with pretransfusion laboratory testing and clinical indication documented Include all patients 
D: No. of transfused plasma units evaluated 
PBM-04 PLT transfusion indication N: No. of PLT doses with pretransfusion PLT testing and clinical indication documented Include all patients 
D: No. of transfused PLT doses evaluated 
PBM-05 Blood administration documentation N: No. of transfused blood units/doses (bags) with documentation for all of the following: Include all patients 
Patient identification and transfusion order (or blood identification no.) confirmed before the initiation of transfusion 
Date and time of transfusion 
Blood pressure, pulse, and temperature recorded before, during, and after transfusion 
D: No. of transfused RBC, plasma, and PLT units/doses (bags) evaluated 
PBM-06 Preoperative anemia screening N: Patients with documentation of preoperative anemia screening14-45 d before anesthesia start date Elective orthopedic and hysterectomy surgeries; patient >18 y of age 
D: Selected elective surgical patients 
PBM-07 Preoperative blood type screening and antibody testing N: Patients with documentation of preoperative type and screen or type and crossmatch completed before anesthesia start time Elective cardiac, orthopedic, and hysterectomy surgeries; patient >18 y of age 
D: Selected elective surgical patients 
No.Measure nameMeasureComments
PBM-01 Transfusion consent N: Patients with a signed consent who received information about the risks, benefits, and alternatives before the initial blood transfusion or the initial transfusion was deemed a medical emergency Include all patients 
D: Patients who received a transfusion of RBCs, PLTs, or plasma 
PBM-02 RBC transfusion indication N: No. of RBC units (bags) with pretransfusion Hb or Hct result and clinical indication documented Include all patients 
D: No. of transfused RBC units evaluated 
PBM-03 Plasma transfusion indication N: No. of plasma units (bags) with pretransfusion laboratory testing and clinical indication documented Include all patients 
D: No. of transfused plasma units evaluated 
PBM-04 PLT transfusion indication N: No. of PLT doses with pretransfusion PLT testing and clinical indication documented Include all patients 
D: No. of transfused PLT doses evaluated 
PBM-05 Blood administration documentation N: No. of transfused blood units/doses (bags) with documentation for all of the following: Include all patients 
Patient identification and transfusion order (or blood identification no.) confirmed before the initiation of transfusion 
Date and time of transfusion 
Blood pressure, pulse, and temperature recorded before, during, and after transfusion 
D: No. of transfused RBC, plasma, and PLT units/doses (bags) evaluated 
PBM-06 Preoperative anemia screening N: Patients with documentation of preoperative anemia screening14-45 d before anesthesia start date Elective orthopedic and hysterectomy surgeries; patient >18 y of age 
D: Selected elective surgical patients 
PBM-07 Preoperative blood type screening and antibody testing N: Patients with documentation of preoperative type and screen or type and crossmatch completed before anesthesia start time Elective cardiac, orthopedic, and hysterectomy surgeries; patient >18 y of age 
D: Selected elective surgical patients 

Hct, hematocrit; PLT, platelet.

The AABB standards cover all aspects of PBM, including the optimization of erythropoiesis, minimization of blood loss, and management of anemia, including the appropriate indications for transfusion. Organizational issues are also encompassed, including management oversight and support, adequate staffing, equipment and information systems, policies and procedures for clinical care, documentation, and responding to nonconformance and adverse events.38 

Despite the worldwide recognition of the value of PBM, there is still some way to go in terms of its widespread adoption to become “the standard of care.” A recent survey of hospitals in England found poor compliance with PBM standards developed by the National Institute for Health and Care Excellence (NICE) (Table 5).39  Comprehensive PBM implementation is challenging, because it encompasses patients with a wide range of clinical conditions undergoing many different procedures and therapies and involves many clinical settings and many types of health care professionals.

Table 5.

Hospitals in England responding to a survey asking if they have data to indicate compliance with NICE Quality Standards for Blood Transfusion39  (if so, did they provide the data, and what was the mean level of compliance against the quality standards)

NICE Quality Standards for Blood TransfusionQS1 preQS1 postQS2QS3QS4
Sites having compliance data (% of trusts) 26 (23%) 17 (15%) 31 (28%) 38 (34%) 40 (36%) 
Sites providing compliance data (n) 12 15 19 
Mean level of compliance (%) 61% (30%-100%) 40% (10%-60%) 69% (0%-100%) 55% (20%-78%) 53% (0%-100%) 
NICE Quality Standards for Blood TransfusionQS1 preQS1 postQS2QS3QS4
Sites having compliance data (% of trusts) 26 (23%) 17 (15%) 31 (28%) 38 (34%) 40 (36%) 
Sites providing compliance data (n) 12 15 19 
Mean level of compliance (%) 61% (30%-100%) 40% (10%-60%) 69% (0%-100%) 55% (20%-78%) 53% (0%-100%) 

QS1. People with iron deficiency anemia are offered iron supplementation before (QS1 pre) and after surgery (QS1 post). QS2. Adults having surgery and expected to have moderate blood loss are offered tranexamic acid. QS3. People who receive a red cell transfusion are clinically reassessed and have their Hb checked after each unit. QS4. People who may have or who have had a transfusion are given verbal and written information about the benefits and risks of transfusion.

PBM activities require coordination, arguably but not necessarily best led by a transfusion medicine specialist. The support of hospital managers is essential to ensure that sufficient resources are made available and that any organizational problems that might interfere with a comprehensive PBM program are overcome. PBM requires input from multiple medical specialties that may include hematology, anesthesiology, surgery, and gastroenterology as illustrated by the case study. Efforts to raise awareness about PBM include the “Choosing Wisely” campaigns of the AABB40  and the American Society of Hematology,41  which are intended to encourage clinicians to rethink their ingrained culture of liberal transfusion practice and prompt patients to question why they are being prescribed blood.

Our case study illustrates the implementation of PBM. Preoperative anemia is diagnosed and treated at the earliest opportunity before elective surgery. Intraoperatively, antifibrinolytic medication is administered to reduce blood loss, and cell salvage allows a unit of autologous RBCs to be reinfused. There is evidence that spinal anesthesia may reduce blood loss. Conventional suction drains are avoided, because these may increase blood loss. Postoperatively, the recommended transfusion threshold of 8.0 g/dL is followed, and only a single unit of donor RBCs is required supported by an electronic decision support tool.

It is recognized that additional studies are needed to provide better evidence for the whole range of PBM interventions, including evidence for improved patient outcomes and lower hospital costs as well as for reductions in blood utilization. More research also needs to be undertaken to understand how best to use educational efforts and other methods, such as electronic clinical decision support systems,42  to support the implementation of PBM interventions. However, while these studies are being conducted, it is of utmost importance to translate PBM guidelines into practical day-to-day recommendations and encourage their use. The output in terms of practice and research recommendations from the recent PBM Consensus Conference in Frankfurt is another step on the path to making PBM the standard of care.

Michael F. Murphy, National Health Service Blood and Transplant, John Radcliffe Hospital, Oxford OX3 9BQ, United Kingdom; e-mail: [email protected].

1.
Carson
JL
,
Terrin
ML
,
Noveck
H
, et al
;
FOCUS Investigators
.
Liberal or restrictive transfusion in high-risk patients after hip surgery
.
N Engl J Med
.
2011
;
365
(
26
):
2453
-
2462
.
2.
Zeller
MP
,
Kaufman
RM
.
Safeguarding the patient’s own blood supply
.
JAMA
.
2019
;
321
(
10
):
943
-
945
.
3.
Serious Hazards of Transfusion
. Serious hazards of transfusion annual report. https://www.shotuk.org/shot-reports/report-summary-and-supplement-2017/. Accessed 29 July 2019.
4.
Ellingson
KD
,
Sapiano
MRP
,
Haass
KA
, et al
.
Continued decline in blood collection and transfusion in the United States-2015
.
Transfusion
.
2017
;
57
(
suppl 2
):
1588
-
1598
.
5.
NHS Blood and Transplant
. National comparative audit of blood transfusion. https://hospital.blood.co.uk/audits/national-comparative-audit/. Accessed 29 July 2019.
6.
Murphy
MF
,
Waters
JH
,
Wood
EM
,
Yazer
MH
.
Transfusing blood safely and appropriately [published correction appears in BMJ. 2013;347:f4799]
.
BMJ
.
2013
;
347
:
f4303
.
7.
Hébert
PC
,
Wells
G
,
Blajchman
MA
, et al
.
A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group
.
N Engl J Med
.
1999
;
340
(
6
):
409
-
417
.
8.
Hajjar
LA
,
Vincent
JL
,
Galas
FR
, et al
.
Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial
.
JAMA
.
2010
;
304
(
14
):
1559
-
1567
.
9.
Villanueva
C
,
Colomo
A
,
Bosch
A
, et al
.
Transfusion strategies for acute upper gastrointestinal bleeding
.
N Engl J Med
.
2013
;
368
(
1
):
11
-
21
.
10.
Carson
JL
,
Stanworth
SJ
,
Roubinian
N
, et al
.
Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion
.
Cochrane Database Syst Rev
.
2016
;
10
:
CD002042
.
11.
Goodnough
LT
,
Levy
JH
,
Murphy
MF
.
Concepts of blood transfusion in adults
.
Lancet
.
2013
;
381
(
9880
):
1845
-
1854
.
12.
Yazer
MH
,
Triulzi
DJ
.
Things aren’t always as they seem: what the randomized trials of red blood cell transfusion tell us about adverse outcomes
.
Transfusion
.
2014
;
54
(
12
):
3243
-
3246
.
13.
Carson
JL
,
Guyatt
G
,
Heddle
NM
, et al
.
Clinical practice guidelines from the AABB: red blood cell transfusion thresholds and storage
.
JAMA
.
2016
;
316
(
19
):
2025
-
2035
.
14.
Shander
A
,
Bracey
AW
Jr
,
Goodnough
LT
, et al
.
Patient blood management as standard of care
.
Anesth Analg
.
2016
;
123
(
4
):
1051
-
1053
.
15.
Goodnough
LT
,
Murphy
MF
.
Do liberal blood transfusions cause more harm than good?
BMJ
.
2014
;
349
:
g6897
.
16.
World Health Organization (WHO)
.
WHO global forum for blood safety: patient blood management
. https://www.who.int/bloodsafety/events/gfbs_01_pbm/en/. Accessed 29 July 2019.
17.
Society for the Advancement of Blood Management (SABM)
.
SABM administrative and clinical standards for patient blood management programs
—4th edition. https://www.sabm.org/publications. Accessed 29 July 2019.
18.
Musallam
KM
,
Tamim
HM
,
Richards
T
, et al
.
Preoperative anaemia and postoperative anaemia outcomes in non-cardiac surgery patients: a retrospective cohort study
.
Lancet
.
2011
;
378
(
9800
):
1396
-
1407
.
19.
Krishnasivam
D
,
Trentino
KM
,
Burrows
S
, et al
.
Anemia in hospitalized patients: an overlooked risk in medical care
.
Transfusion
.
2018
;
58
(
11
):
2522
-
2528
.
20.
Baron
DM
,
Hochrieser
H
,
Posch
M
, et al
;
European Society of Anaesthesiology
.
Preoperative anaemia is associated with poor clinical outcome in non-cardiac surgery patients
.
Br J Anaesth
.
2014
;
113
(
3
):
416
-
423
.
21.
Fowler
AJ
,
Ahmad
T
,
Phull
MK
,
Allard
S
,
Gillies
MA
,
Pearse
RM
.
Meta-analysis of the association between preoperative anaemia and mortality after surgery
.
Br J Surg
.
2015
;
102
(
11
):
1314
-
1324
.
22.
Roubinian
NH
,
Murphy
EL
,
Mark
DG
, et al
.
Long-term outcomes among patients discharged from the hospital with moderate anemia: a retrospective cohort study [published online ahead of print 18 December 2018]
.
Ann Intern Med
.
doi:10.7326/M17-3253
.
23.
Shander
A
,
Goodnough
LT
.
From tolerating anemia to treating anemia [published online ahead of print 18 December 2018]
.
Ann Intern Med
.
doi:10.7326/M18-3145
.
24.
Spolverato
G
,
Kim
Y
,
Ejaz
A
,
Frank
SM
,
Pawlik
TM
.
Effect of relative decrease in blood hemoglobin concentrations on postoperative morbidity in patients who undergo major gastrointestinal surgery
.
JAMA Surg
.
2015
;
150
(
10
):
949
-
956
.
25.
Gross
I
,
Seifert
B
,
Hofmann
A
,
Spahn
DR
.
Patient blood management in cardiac surgery results in fewer transfusions and better outcome
.
Transfusion
.
2015
;
55
(
5
):
1075
-
1081
.
26.
Goodnough
LT
,
Maggio
P
,
Hadhazy
E
, et al
.
Restrictive blood transfusion practices are associated with improved patient outcomes
.
Transfusion
.
2014
;
54
(
10pt2
):
2753
-
2759
.
27.
Leahy
MF
,
Roberts
H
,
Mukhtar
SA
, et al
;
Western Australian Patient Blood Management Program
.
A pragmatic approach to embedding patient blood management in a tertiary hospital
.
Transfusion
.
2014
;
54
(
4
):
1133
-
1145
.
28.
Meybohm
P
,
Herrmann
E
,
Steinbicker
AU
, et al
;
PBM-study Collaborators
.
Patient blood management is associated with a substantial reduction of red blood cell utilization and safe for patient’s outcome: a prospective, multicentre cohort study with a noninferiority design
.
Ann Surg
.
2016
;
264
(
2
):
203
-
211
.
29.
American Society of Anesthesiologists Task Force on Perioperative Blood Management
.
Practice guidelines for perioperative blood management: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Management
.
Anesthesiology
.
2015
;
122
(
2
):
241
-
275
.
30.
Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee
. Patient blood management—an evidence-based approach to patient care. https://www.transfusionguidelines.org/uk-transfusion-committees/national-blood-transfusion-committee/patient-blood-management. Accessed 29 July 2019.
31.
Klein
AA
,
Arnold
P
,
Bingham
RM
, et al
.
AAGBI guidelines: the use of blood components and their alternatives 2016
.
Anaesthesia
.
2016
;
71
(
7
):
829
-
842
.
32.
Meybohm
P
,
Froessler
B
,
Goodnough
LT
, et al
.
“Simplified international recommendations for the implementation of patient blood management” (SIR4PBM)
.
Perioper Med (Lond)
.
2017
;
6
(
1
):
5
.
33.
Padhi
S
,
Kemmis-Betty
S
,
Rajesh
S
,
Hill
J
,
Murphy
MF
;
Guideline Development Group
.
Blood transfusion: summary of NICE guidance
.
BMJ
.
2015
;
351
:
h5832
.
34.
Mueller
M
,
van Remoortel
H
,
Meybohm
P
, et al
;
ICC PBM Frankfurt 2018 Group
.
Patient blood management recommendations from the 2018 Frankfurt Consensus Conference
.
JAMA
.
2019
;
321
(
10
):
983
-
997
.
35.
Guyatt
GH
,
Oxman
AD
,
Vist
GE
, et al
;
GRADE Working Group
.
GRADE: an emerging consensus on rating quality of evidence and strength of recommendations
.
BMJ
.
2008
;
336
(
7650
):
924
-
926
.
36.
Moberg
J
,
Oxman
AD
,
Rosenbaum
S
, et al
;
GRADE Working Group
.
The GRADE Evidence to Decision (EtD) framework for health system and public health decisions
.
Health Res Policy Syst
.
2018
;
16
(
1
):
45
.
37.
Gammon
HM
,
Waters
JH
,
Watt
A
,
Loeb
JM
,
Donini-Lenhoff
A
.
Developing performance measures for patient blood management
.
Transfusion
.
2011
;
51
(
11
):
2500
-
2509
.
38.
AABB
.
Standards for a Patient Blood Management Program
. 2nd ed.
Bethesda, MD
:
AABB
;
2018
.
39.
National Institute for Health and Care Excellence
.
Quality standards for blood transfusion
. https://www.nice.org.uk/guidance/qs138. Accessed 29 July 2019.
40.
Callum
JL
,
Waters
JH
,
Shaz
BH
,
Sloan
SR
,
Murphy
MF
.
The AABB recommendations for the Choosing Wisely campaign of the American Board of Internal Medicine
.
Transfusion
.
2014
;
54
(
9
):
2344
-
2352
.
41.
Hicks
LK
,
Bering
H
,
Carson
KR
, et al
.
The ASH Choosing Wisely® campaign: five hematologic tests and treatments to question
.
Blood
.
2013
;
122
(
24
):
3879
-
3883
.
42.
Hibbs
SP
,
Nielsen
ND
,
Brunskill
S
, et al
.
The impact of electronic decision support on transfusion practice: a systematic review
.
Transfus Med Rev
.
2015
;
29
(
1
):
14
-
23
.

Competing Interests

Conflict-of-interest disclosure: M.F.M. and A.P. declare no competing financial interests.

Author notes

Off-label drug use: None disclosed.