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Indications and hemoglobin thresholds for red blood cell transfusion in the adult

Indications and hemoglobin thresholds for red blood cell transfusion in the adult
Authors:
Jeffrey L Carson, MD
Steven Kleinman, MD
Section Editors:
Arthur J Silvergleid, MD
Aaron Tobian, MD, PhD
Deputy Editor:
Jennifer S Tirnauer, MD
Literature review current through: Feb 2022. | This topic last updated: Dec 08, 2021.

INTRODUCTION — For many decades, the decision to transfuse red blood cells (RBCs) was based upon the "10/30 rule": transfusion was used to maintain a blood hemoglobin concentration above 10 g/dL (100 g/L) and a hematocrit above 30 percent [1]. However, concern regarding transmission of blood-borne pathogens and efforts at cost containment caused a re-examination of transfusion practices in the 1980s. The 1988 National Institutes of Health Consensus Conference on Perioperative Red Blood Cell Transfusions suggested that no single criterion should be used as an indication for red cell component therapy, and that multiple factors related to the patient's clinical status and oxygen delivery needs should be considered [2].

During the subsequent 30 years, a large body of clinical evidence was generated, resulting in the publication of many guidelines for RBC transfusion in different settings (see 'Society guidelines' below). A common theme of these guidelines is the need to balance the benefit of treating anemia with the desire to avoid unnecessary transfusion, with its associated costs and potential harms. This requires considerable diagnostic skill and acumen on the part of physicians ordering transfusions.

As blood transfusion practices are evaluated in randomized trials, we are increasingly able to emphasize clinical trial data, since these data provide the best evidence to guide transfusion decisions.

The indications and thresholds for RBC transfusion in adults will be reviewed here. Separate topics discuss indications and thresholds for newborns and children. (See "Red blood cell transfusions in the newborn" and "Red blood cell transfusion in infants and children: Indications".)

General aspects of RBC collection, storage, safety, and administration, as well as practices for some special populations, are presented separately.

Pretransfusion testing – (see "Pretransfusion testing for red blood cell transfusion")

Practical aspects of administration – (see "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion")

Surgery/anesthesia issues – (see "Surgical blood conservation: Preoperative autologous blood donation" and "Surgical blood conservation: Blood salvage")

Trauma/massive transfusion – (see "Massive blood transfusion" and "Initial management of moderate to severe hemorrhage in the adult trauma patient")

Hematologic disorders – (see "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques" and "Management of thalassemia")

RATIONALE FOR TRANSFUSION

Role of blood in oxygen delivery — Blood delivers oxygen to the tissues, and the vast majority of oxygen delivered is bound to hemoglobin in RBCs. Thus, anemia has the potential to reduce oxygen delivery and, most importantly, end-organ oxygen utilization. However, most patients are able to increase tissue oxygen delivery as well as the extraction of oxygen from the RBCs over a range of hemoglobin concentrations.

The major physiologic considerations relevant to anemic patients are the degree to which oxygen delivery to the tissues is adequate, the extent of oxygen extraction at the tissue level, and whether compensatory mechanisms for maintaining oxygen delivery and utilization will become overwhelmed or deleterious [1]. (See "Oxygen delivery and consumption".)

Oxygen delivery (DO2) is determined by the formula:

DO2  =  cardiac output  x  arterial oxygen content

In healthy patients, DO2 can generally be raised by increasing cardiac output (via increased heart rate or stroke volume). In critically ill patients, DO2 may become more dependent on arterial oxygen content, and end-organ oxygen utilization can become pathologically dependent upon DO2 (supply dependence). Determining what hemoglobin level is adequate in individual clinical scenarios has been the goal of a large number of clinical studies and randomized trials. (See 'Asymptomatic hospitalized patient' below.)

At rest, there is a large reserve in oxygen delivery, since the rate of delivery normally exceeds consumption by a factor of four. Thus, if intravascular volume is maintained during bleeding and cardiovascular status is not impaired, oxygen delivery theoretically will be adequate until the hematocrit falls below 10 percent because greater cardiac output, rightward shift of the oxygen-hemoglobin dissociation curve, and increased oxygen extraction can compensate for the decrease in arterial oxygen content (table 1).

These predictions were confirmed in a study in which healthy resting individuals underwent acute isovolemic reduction of their hemoglobin to 5 g/dL (equivalent to a hematocrit of approximately 15 percent) [3]. Though some individuals did develop electrocardiogram (ECG) changes consistent with myocardial ischemia, there was little evidence of inadequate oxygen delivery/utilization, and the fall in hemoglobin was associated with progressive increases in stroke volume and heart rate (and therefore cardiac output). Heart rate was found to increase linearly in response to the acute isovolemic anemia [4]. Of note, cognitive function measured by reaction time and immediate memory was impaired when the hemoglobin concentration was reduced to 5 to 6 g/dL [5].

The oxygen-carrying capacity of blood does not directly reflect the delivery of oxygen to tissues nor the extraction of oxygen from RBCs at the tissue level. Although techniques to measure tissue oxygenation are under development, they are not yet ready for clinical use [6].

The preceding considerations represent the optimal clinical response in healthy adults. However, blood transfusion is usually administered to patients who are ill with underlying comorbidities, and there is concern that compensatory mechanisms may be impaired in critically ill patients, particularly in patients with underlying cardiovascular disease. It has been argued in the past that this might justify prophylactic transfusion to maintain a hemoglobin of 10 g/dL. However, data in favor of this hemoglobin target level are lacking. To the contrary, multicenter randomized controlled trials indicate that compared with a target hemoglobin of 10 g/dL, target hemoglobin values of 7 to 8 g/dL are associated with equivalent or better outcomes in most patient populations. (See 'Overview of our approach' below.)

Impact of anemia on morbidity and mortality — While numerous observational studies have shown an association between anemia and increased mortality, it is not clear that correction of anemia will improve mortality. The following studies illustrate the deleterious effect of severe postoperative anemia:

In a study of 1958 patients who declined blood transfusion for religious reasons, the odds of death rose as the preoperative hemoglobin fell, and the odds of death were much greater in patients with underlying cardiovascular disease [7].

In a subset analysis of 300 postoperative patients, a hemoglobin between 7 and 8 g/dL appeared to have no immediate adverse effect on mortality, whereas there was a clear risk of postoperative death when the hemoglobin fell below 7 g/dL [8]. Similar results were observed in a 2014 analysis in 293 patients [9]. The combined 30-day in-hospital mortality for patients with various postoperative hemoglobin levels were [9]:

7.1 to 8.0 (n = 232) – 0.9 percent

5.1 to 7.0 (n = 217) – 9.2 percent

3.1 to 5.0 (n = 101) – 26.7 percent

≤3.0 (n = 37) – 62.1 percent

In a follow-up study of the same 1958 postoperative patients, one-third died in the hospital [10]. The time from surgery to death was long, suggesting that there would be time to intervene (median of three days from surgery to hemoglobin nadir and two days from hemoglobin nadir to death). There was not a single etiology that was predictive of mortality for these severely anemic patients.

A retrospective database review of 310,311 veterans >65 years of age undergoing non-cardiac surgery evaluated the association of preoperative anemia with mortality or cardiac events [11]. The adjusted odds of death or cardiac events correlated inversely with the preoperative hematocrit. Even mild anemia (HCT 36.0 to 38.9) was associated with a 10 percent increase in events; this rose to a 52 percent increased risk with more severe anemia (HCT 18.0 to 20.9).

While these and other studies suggest that severe anemia is associated with poor outcome, data from randomized trials have shown that more aggressive correction of anemia does not necessarily improve these outcomes [12,13]. Clinical trials are needed to establish whether anemia is merely a marker for more severe underlying disease or a direct cause of poor outcomes.

Over the long term, use of a restrictive transfusion strategy leads to fewer transfusions without an increase in major complications of anemia. This was demonstrated in a cohort study involving electronic health record data for nearly 450,000 adults who were discharged from the hospital with anemia [14]. The proportion of patients who were discharged with moderate anemia increased over time due to greater use of restrictive transfusion strategies; despite this change, survival was comparable in those discharged with moderate anemia compared with those with higher discharge hemoglobin levels earlier in the study. Likewise, readmission rates were similar between the two groups. Subgroup analyses demonstrated that this tolerance of lower discharge hemoglobin levels applied to a variety of patient groups and persisted for at least six months after discharge. These results further support the use of restrictive strategies. (See 'Restrictive transfusion strategy for most stable patients' below.)

RISKS AND COMPLICATIONS OF TRANSFUSION — The risks and potential long term complications of RBC transfusion, and strategies to minimize these risks and complications, are discussed separately. These include the following:

Infection is a risk of transfusion since transfusion-transmitted pathogens (eg, viruses, bacteria, and parasites) can be transmitted if they are present in donor blood and if they escape detection by screening assays. In addition, some studies have reported that transfusion-mediated immunosuppression may lead to increased risk of postoperative bacterial infection, although a 2016 meta-analysis of randomized trials did not find an increased risk of infection [13]. (See "Transfusion-transmitted bacterial infection" and "Risk of HIV from blood transfusion" and "Epidemiology and transmission of hepatitis C virus infection", section on 'Blood transfusion' and "Epidemiology, transmission, and prevention of hepatitis B virus infection", section on 'Transfusion' and "Leukoreduction to prevent complications of blood transfusion", section on 'Complications for which leukoreduction is shown to be beneficial'.)

Allergic and immune transfusion reactions can occur in any patient, and are more common in multiply-transfused patients. (See "Immunologic transfusion reactions", section on 'Urticarial (allergic) reactions' and "Hemolytic transfusion reactions" and "Transfusion-related acute lung injury (TRALI)".)

Volume overload is typically a concern in older adults, small children, and those with compromised cardiac function. (See "Transfusion-associated circulatory overload (TACO)".)

Hyperkalemia from potassium released from RBCs during blood bank storage is primarily a concern in massive transfusion, impaired renal function, and infants/newborns. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Hyperkalemia'.)

Iron overload becomes a concern after a large number of transfusions for chronic anemia [15]. (See 'Ambulatory patient' below and "Approach to the patient with suspected iron overload", section on 'Transfusional iron overload'.)

OVERVIEW OF OUR APPROACH

Factors to consider — Optimal transfusion practice should provide enough RBCs to maximize clinical outcomes while avoiding unnecessary transfusions. As noted in a 2019 editorial, transfusion should be considered as a short-term treatment with a mixed risk-benefit profile; it does not substitute for specific treatment directed at the underlying cause of anemia, which must be determined and addressed for the individual patient [16]. The evaluation of anemia is summarized in an overview topic (see "Diagnostic approach to anemia in adults") and expanded in several topics included with the overview.

The hemoglobin level chosen is based on the results from clinical trials, but clinical judgment is required. We consider many factors in deciding whether to transfuse patients with anemia, rather than basing the decision solely on the presence or absence of symptoms or on a specified hemoglobin level. The final decision to transfuse should incorporate the clinical status, co-morbidity, and the individual wishes of the patient. It is also important to recognize that lower hemoglobin thresholds have not been tested in most clinical settings and may be tolerated by many patients. This approach is most consistent with the AABB Guidelines, which we coauthored [17]. (See 'Society guidelines' below.)

Restrictive transfusion strategy for most stable patients — For most patients, we recommend using a restrictive transfusion strategy (giving less blood; transfusing at a lower hemoglobin level; and aiming for a lower target hemoglobin level) rather than a liberal transfusion strategy (giving more blood; transfusing at a higher hemoglobin level), as illustrated in the figure (algorithm 1); this practice is based on the results of multiple clinical trials. (Related Pathway(s): Anemia: Indications for red blood cell transfusion in hospitalized adults.)

For most hemodynamically stable medical and surgical patients, we recommend considering transfusion at a hemoglobin of 7 to 8 g/dL, with the threshold based on the value established as safe in the clinical trial with the population that most closely resembles the patient. Some patients may tolerate a lower hemoglobin level (table 2).

Assessment of the post-transfusion hemoglobin level can be performed as early as 15 minutes following transfusion, as long as the patient is not actively bleeding. This practice is based on studies showing a high degree of concordance between values measured 15 minutes after completion of the transfusion versus longer intervals [18,19].

Major exceptions to the use of a threshold of 7 to 8 g/dL, where evidence is insufficient to guide therapy, include the following:

Symptomatic patients may be transfused at higher hemoglobin levels to treat symptoms. (See 'Symptomatic patient' below.)

Patients with acute coronary syndromes may require higher thresholds for transfusion. (See 'Acute coronary syndrome (including MI)' below.)

Threshold-based transfusion is not appropriate for patients requiring massive transfusion, such as in the setting of trauma or serious gastrointestinal bleeding. Rather, estimated blood loss and hemodynamic status should guide transfusion given the delay for hemoglobin to equilibrate and time waiting for hemoglobin levels to be reported. (See "Massive blood transfusion" and "Initial management of moderate to severe hemorrhage in the adult trauma patient".)

Chronic transfusion-dependent anemia, such as sickle cell disease or thalassemia. (See "Management of thalassemia", section on 'Regular transfusions'.)

Certain cases of severe thrombocytopenia. (See 'Oncology patient' below.)

Our goal of avoiding unnecessary transfusion also guides our practice of transfusing one unit of RBCs at a time, rather than requesting multiple units, for a hemodynamically stable patient who is not actively bleeding [20,21]. Whenever possible, we also initiate or continue treatment of the underlying condition responsible for the anemia.

Summary of supporting evidence — Our approach of considering a threshold hemoglobin of 7 or 8 g/dL for most patients is based on evidence from a 2018 systematic review and meta-analysis of 37 randomized clinical trials comparing higher versus lower transfusion thresholds in 19,049 medical and surgical patients (adults and children) [22]. Trials were included if transfusion was administered on the basis of a transfusion trigger, defined as a hemoglobin or hematocrit level below which a blood transfusion was to be given. Most trials compared outcomes in patients transfused at hemoglobin thresholds between 7 and 10 g/dL; specific thresholds differed for each trial. Compared with liberal transfusion strategies (higher thresholds), restrictive strategies (lower thresholds) resulted in the following:

Decreased probability of receiving a transfusion (41 percent decrease; relative risk [RR] 0.59; 95% CI 0.53-0.66)

No difference in 30-day mortality (RR 1.0; 95% CI 0.86-1.16) (figure 1)

No difference in infection rate (RR 0.97; 95% CI 0.88-1.07)

No difference in functional recovery, or hospital or intensive care length of stay

No increased risk of myocardial infarction (RR 1.05; 95% CI 0.88-1.26)

Two other meta-analyses found somewhat different results; however, these do not change our approach. A 2016 meta-analysis performed a "context-specific" evaluation in adult surgical or critically ill patients, stratifying by patient characteristics and clinical settings. The authors concluded that, with restrictive transfusion, there was an increased risk of a composite outcome in patients undergoing cardiac/vascular procedures and in older adult orthopedic patients [23]. In a 2017 meta-analysis, older patients were benefited by liberal transfusion [24]. However, both of these analyses predated publication of the very large Transfusion Requirements in Cardiac Surgery III (TRICS III) trial [25] (see 'Cardiac surgery' below), which had contradictory findings, showing that restrictive transfusion was safe in cardiac surgery and that older cardiac surgery patients appeared to benefit even more from restrictive transfusion. Thus, we conclude that these two meta-analyses may be incomplete, and their results should be cautiously interpreted unless subsequently confirmed.

Evidence from a large cohort of hospitalized patients also demonstrated that mortality is not adversely affected by the use of restrictive transfusion. An integrated health care system of 21 community hospitals conducted a review of electronic medical records in 218,056 patients with hemoglobin less than 10 g/dL who were hospitalized before or after institution of restrictive transfusion guidelines [26,27]. The 30-day mortality rate was unaffected by adoption of a restrictive practice (7.8 versus 7.8 percent) despite reduction in the number of units transfused (from 42 to 31 units per 100 patients). A subsequent study in 445,371 adults who were discharged from one of these hospitals found that there was an increase in the prevalence of moderate anemia (7 to 10 g/dL) after discharge; but subsequent transfusion, rehospitalization, and mortality did not rise during the six months after discharge, and overall RBC transfusions declined during a four-year period [14].

Based on these results, we use a restrictive strategy with a threshold hemoglobin of 7 to 8 g/dL for most hemodynamically stable medical and surgical patients.

In deciding which restrictive threshold to use, we favor applying specific thresholds as closely as possible to the patient population in which they were established in randomized trials, rather than applying a single threshold to all patients (table 2) [28]. This view is based on our recognition that different patient populations may have different clinical features that could potentially affect transfusion outcomes [29]. As an example, a hemoglobin threshold of 7 g/dL may be safer for patients with gastrointestinal bleeding because it reduces portal pressure and decreases the chance of rebleeding, whereas a threshold of 8 g/dL for patients with pre-existing coronary disease may provide better oxygen delivery to a vulnerable myocardium. Similarly, the distinction between using a threshold of 7 g/dL for hemodynamically stable patients in the intensive care unit (ICU) and 8 g/dL for hemodynamically stable medical and surgical patients is based solely on the values used in randomized trials; we do not know if these two populations (ICU and medical/surgical) are biologically distinct and truly have different hemoglobin requirements.

Evidence in specific populations is discussed in the sections below. (See 'Thresholds for specific patient populations' below.)

Society guidelines — Transfusion guidelines have been published by the following societies:

International (Frankfurt) Consensus Conference on patient blood management, 2018 [30]

AABB (formerly the American Association of Blood Banks), 2016 [17]

United Kingdom National Clinical Guideline Centre, 2016 [31]

American Society of Anesthesiologists (perioperative blood management), 2015 [32]

British Committee for Standards in Haematology, 2014 (myelodysplastic syndromes [MDS] management) [33]

National Comprehensive Cancer Network (chemotherapy-induced anemia), 2014 [34]

American College of Physicians (anemia in heart disease), 2013 [35]

Surviving Sepsis Campaign Guidelines Committee including the pediatric subgroup (sepsis and shock), 2013 [36]

British Committee for Standards in Haematology (critically ill adults), 2012 [37]

National Blood Authority Canberra Australia, Patient Blood Management Guidelines: Modules 1-4. 2012 [38]

Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Anemia in Chronic Kidney Disease, 2012 [39]

Links to some of these guidelines are presented below. (See 'Society guideline links' below.)

In general, the different guidelines have recommended use of a restrictive transfusion threshold of 7 to 8 g/dL. As an example, the 2016 AABB guidelines (which we co-authored) include the following recommendations for hemodynamically stable patients without active bleeding [17]:

Hemoglobin <6 g/dL – Transfusion recommended except in exceptional circumstances.

Hemoglobin 6 to 7 g/dL – Transfusion generally likely to be indicated.

Hemoglobin 7 to 8 g/dL – Transfusion may be appropriate in patients undergoing orthopedic surgery or cardiac surgery, and in those with stable cardiovascular disease, after evaluating the patient’s clinical status.

Hemoglobin 8 to 10 g/dL – Transfusion generally not indicated, but should be considered for some populations (eg, those with symptomatic anemia, ongoing bleeding, acute coronary syndrome with ischemia).

Hemoglobin >10 g/dL – Transfusion generally not indicated except in exceptional circumstances.

The guidelines also emphasize that the decision to transfuse should not be based only on hemoglobin level but should incorporate individual patient characteristics and symptoms. Clinical judgment is critical in the decision to transfuse; therefore, transfusing RBCs above or below the specified hemoglobin threshold may be dictated by the clinical context. Similarly, the decision not to transfuse RBCs to a patient with a hemoglobin concentration below the recommended thresholds is also a matter of clinical judgment.

A brief comparison of recommendations from 10 clinical guidelines published between 2012 and 2017 is available [40].

THRESHOLDS FOR SPECIFIC PATIENT POPULATIONS

Symptomatic patient — In some randomized trials of transfusion thresholds, symptoms of anemia were an indication for transfusion regardless of whether the hemoglobin was above the prescribed threshold [41,42]. We agree with the premise that symptomatic anemia should be treated with transfusion in patients with hemoglobin <10 g/dL, regardless of the hemoglobin level, provided that the symptoms are severe enough and are clearly related to the anemia rather than the underlying condition. It is reasonable to defer transfusion for some symptomatic individuals with a hemoglobin between 7 and 10 g/dL; an example would be a young person without comorbidities or coronary artery disease whose hemoglobin is 8 g/dL, is not expected to decline further, and/or is expected to increase their hemoglobin within one or two weeks.

Symptoms of anemia may include symptoms of myocardial ischemia, orthostatic hypotension or tachycardia unresponsive to fluid replacement, or marked dyspnea at rest. It is important to note, however, that these symptoms can also be caused by other conditions (eg, massive pulmonary embolus). While exertional symptoms can be helpful in alerting the clinician to the presence of anemia, they are generally not considered indications for red cell transfusion. (See "Diagnostic approach to anemia in adults", section on 'Correlation with symptoms'.)

Chronic anemia can present with symptoms such as irritability, weakness, and exercise intolerance. These symptoms of anemia are nonspecific and often not considered sufficient indications for transfusion. Decisions on whether to transfuse RBCs to treat fatigue are covered separately. (See "Causes and diagnosis of iron deficiency and iron deficiency anemia in adults", section on 'Clinical manifestations' and "Diagnostic approach to anemia in adults", section on 'Correlation with symptoms'.)

Some patients will not manifest typical anemia symptoms for a variety of reasons (eg, altered mental status, diabetic neuropathy, analgesic therapy). Thus, surrogate measures (eg, ECG changes) may be useful in some situations. When transfusion is used in a symptomatic patient, it is important to determine whether symptoms have improved following the transfusion and to note this in the medical record, because this may guide further decision-making. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion".)

Acute coronary syndrome (including MI) — Acute coronary syndrome (ACS) includes unstable angina and acute myocardial infarction (MI). Our practice in patients with ACS is to transfuse when the hemoglobin is <8 g/dL and to consider transfusion when the hemoglobin is between 8 and 10 g/dL. We maintain the hemoglobin ≥10 g/dL if the patient has ongoing ischemia, hemodynamic instability, or other symptoms.

A restrictive transfusion threshold (transfusion triggered by a hemoglobin of ≤8 g/dL rather than a higher hemoglobin) in individuals with acute MI is supported by initial results from the REALITY trial, published in 2021 [43]. This trial randomly assigned 668 adults with symptomatic acute MI and anemia to a restrictive or liberal transfusion strategy (transfusion triggered by hemoglobin ≤8 or ≤10 g/dL, respectively). The median age was 77 years and the mean hemoglobin at randomization was 9 g/dL. The restrictive group showed a trend towards a lower risk of major cardiac events (MACE, consisting of death, stroke, recurrent MI, or emergency revascularization) at 30 days (11.1 percent of the restrictive group, versus 14.2 percent in the liberal group; relative risk [RR] 0.78; 95% CI 0.00 to 1.17). However, in landmark analysis in survivors at 30 days followed for one year, major cardiac events were more frequent in the restrictive group (hazard ratio [HR] 1.44; 95% CI 1.01-2.03). Adverse events were similar (11.7 percent in the restrictive group, 11.1 percent in the liberal). Over 64 percent of the patients in the restrictive arm avoided transfusion. Patients and clinicians were aware of their treatment assignment (a possible source of bias), but outcome adjudicators were blinded. Taken in aggregate, the short- and long-term findings from the REALITY trial indicate that the question of non-inferiority and/or superiority of the two transfusion approaches still remain unanswered.

Two smaller trials have been published in patients with acute MI and anemia. A pilot trial of 110 patients found that compared with transfusion for a hemoglobin <8 g/dL (restrictive strategy), transfusion to raise the hemoglobin ≥10 (liberal strategy) was associated with greater survival at 30 days (98 versus 87 percent) [42]. Another trial of 44 patients reported one death in the liberal transfusion group and two deaths in the restrictive strategy group [44].

A 3500-patient trial (MINT) is ongoing. Subgroup analyses of other trials and a pilot trial for MINT have shown mixed outcomes in individuals with ACS (better outcomes with a restrictive strategy in some and with a liberal strategy in others) [22,42,45].

Additional discussion is presented separately. (See "Overview of the non-acute management of unstable angina and non-ST elevation myocardial infarction", section on 'Red cell transfusion' and "Overview of the non-acute management of ST elevation myocardial infarction", section on 'Red cell transfusion'.)

There is variation in transfusion practice in patients undergoing percutaneous coronary intervention (PCI) [46]. A discussion of transfusion in patients undergoing PCI complicated by periprocedural bleeding is presented separately. (See "Periprocedural bleeding in patients undergoing percutaneous coronary intervention", section on 'Blood transfusion'.)

Asymptomatic hospitalized patient — As described above, for most hemodynamically stable medical and surgical patients, we suggest considering transfusion at a hemoglobin of 7 to 8 g/dL. Some patients will remain asymptomatic from anemia at lower hemoglobin levels; conversely transfusion at higher hemoglobin levels is often appropriate for symptomatic patients and in the setting of an ACS. In addition, threshold-based transfusion may not be appropriate for patients requiring massive transfusion. Discussions surrounding specific clinical scenarios are presented separately. The final decision regarding transfusion must take into account the patient’s wishes and clinical status.

Cardiovascular disease — The decision of whether to transfuse patients with cardiovascular disease should consider the nature of the cardiovascular disorder. As an example, it is possible that patients with ACS require different thresholds for transfusion than do patients with stable coronary artery disease or patients with congestive heart failure [22,47].

Pre-existing coronary artery disease — A transfusion threshold of 8 g/dL is supported by subgroup analysis of two randomized transfusion trials that included patients with coronary artery disease.

Patients with pre-existing coronary artery disease were included in the Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS) trial, which found that compared with a threshold of 10 g/dL, a restrictive transfusion strategy (transfusion at a threshold of 8 g/dL or for symptoms) was not associated with worse outcomes, with the exception of an increase in MI that was marginally statistically significant [41]. (See 'Non-cardiac surgery' below.)

Patients with coronary artery disease were also included in the Transfusion Requirements in Critical Care (TRICC) trial, which found that compared with a threshold of 10 g/dL, a restrictive strategy (transfusion at a threshold of 7 g/dL) was associated with lower mortality [48]. (See 'Intensive care unit/septic shock' below.)

Use of this 8 g/dL threshold is somewhat challenged by a 2016 meta-analysis of selected trials that found a higher risk of acute coronary syndrome but not 30-day mortality among patients with cardiovascular disease who received a restrictive transfusion strategy compared with a liberal transfusion strategy [47]. However, this meta-analysis did not include all the relevant trials, and the trials that were included contained patients with acute myocardial infarction as well as pre-existing cardiovascular disease.

Based on our evaluation of these data and the AABB clinical practice guideline taskforce, we consider the threshold of 8 g/dL safe for asymptomatic medical patients with stable coronary artery disease [20].

Transfusion of symptomatic patients with coronary artery disease is guided by the symptoms and clinical judgment, and the optimal threshold for patients with acute coronary syndromes is unresolved. (See 'Symptomatic patient' above and 'Acute coronary syndrome (including MI)' above and "Overview of the non-acute management of ST elevation myocardial infarction", section on 'Red cell transfusion'.)

Heart failure — Anemia and heart failure (HF) often coexist for a variety of reasons (eg, cytokine changes, dilutional anemia, medical therapy for HF).

The approach to transfusion (including more restrictive thresholds for asymptomatic individuals and transfusion for symptoms if hemoglobin is <10 g/dL) and other management strategies in patients with heart failure (eg, attention to the volume load from the transfusion) is discussed in detail separately. (See "Evaluation and management of anemia and iron deficiency in adults with heart failure", section on 'Transfusion'.)

Trauma/massive transfusion — Use of massive transfusion in the critically ill, hemodynamically unstable patient cannot be guided by hemoglobin levels alone and often cannot await interval measurements of hemoglobin. This issue is discussed separately. (See "Massive blood transfusion" and "Initial management of moderate to severe hemorrhage in the adult trauma patient".)

Intensive care unit/septic shock — Restrictive transfusion appears to be safe in medical patients in an intensive care unit (ICU), with the possible exception of patients with ischemic heart disease/acute coronary syndrome.

The use of a threshold of 7 g/dL in hemodynamically stable patients in the ICU is supported by data from the Transfusion Requirements in Critical Care (TRICC) trial [48]. This trial randomly assigned 838 critically ill, euvolemic patients with a hemoglobin less than 9 g/dL within 72 hours of admission to an intensive care unit to a restrictive transfusion strategy (RBCs transfused for hemoglobin concentration <7 g/dL and hemoglobin maintained at 7 to 9 g/dL) or a liberal strategy (RBCs transfused for hemoglobin <10 g/dL and hemoglobin maintained at 10 to 12 g/dL). The mean age was 58, and 82 percent were on mechanical ventilation.

Compared with liberal transfusion, 30-day mortality favored the restrictive strategy but was not statistically significant (23 percent in the liberal group versus 19 percent in the restrictive group). However, 30-day mortality rates were lower with the restrictive strategy in two predefined subgroups:

Patients who were less severely ill (APACHE II score ≤20; mortality 9 versus 16 percent)

Patients <55 years of age (mortality 6 versus 13 percent)

In contrast, in patients with ischemic heart disease, there was a reversal in the trend in 30-day mortality, with 30-day mortality in the restrictive strategy arm slightly higher than in the liberal strategy group (26 versus 21 percent) [49].

Important morbidities were also lower in the restrictive transfusion strategy group as a whole. As examples, rates of myocardial infarction and pulmonary edema were lower in the restrictive group than the liberal strategy group (0.7 versus 2.9 percent and 5.3 versus 10.7 percent, respectively).

The use of a threshold of 7 g/dL was also shown to be safe in patients with septic shock. The Transfusion Requirements in Septic Shock (TRISS) trial randomly assigned 998 patients with septic shock and a hemoglobin level less than 9 g/dL to a restrictive or a liberal transfusion strategy (transfusion at a hemoglobin ≤7g/dL or ≤9 g/dL, respectively) [50]. Consensus criteria for sepsis were used (eg, infection, systemic inflammatory response, hypotension). Transfusions were given as single units of prestorage leukoreduced RBCs. Mortality at 90 days was similar in those transfused with the restrictive and the liberal strategy (43 versus 45 percent; relative risk [RR], 0.94, 95% CI 0.78-1.09). Other outcomes (eg, ischemic events, transfusion reactions, use of vasopressor or inotropic therapy, need for mechanical ventilation) were also similar between the two groups. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Additional therapies'.)

These results demonstrate that a restrictive strategy of RBC transfusion is at least as effective as a liberal transfusion strategy in critically ill patients in the ICU, with the possible exception of patients with underlying ischemic heart disease [51]. (See 'Acute coronary syndrome (including MI)' above and "Use of blood products in the critically ill", section on 'RBC indications'.)

Acute bleeding — Acute bleeding is an especially challenging clinical setting in which to evaluate RBC transfusion thresholds. For patients with massive bleeding or who are hemodynamically unstable, transfusion should be guided by hemodynamic parameters (eg, pulse and blood pressure), the pace of the bleeding, and the ability to stop the bleeding, rather than by the hemoglobin. Therefore, the use of transfusion in acutely hemorrhaging patients cannot be based on thresholds. (See "Use of blood products in the critically ill", section on 'Red blood cells' and "Massive blood transfusion" and "Initial management of moderate to severe hemorrhage in the adult trauma patient".)

For patients who are bleeding but hemodynamically stable, some guidance is provided by two randomized trials in patients with upper gastrointestinal bleeding, which have suggested that a restrictive transfusion strategy is safe when there is access to rapid endoscopic treatment. (See "Approach to acute upper gastrointestinal bleeding in adults", section on 'Blood product transfusions'.)

A single center trial randomly assigned 921 patients with acute upper gastrointestinal bleeding to a restrictive or a liberal transfusion strategy (transfusion threshold of 7 g/dL versus 9 g/dL) and determined all-cause mortality at 45 days [52]. Patients with massive bleeding, acute coronary syndrome, history of peripheral vascular disease or stroke, and hemoglobin >12 g/dL were excluded. All patients underwent emergent upper endoscopy within six hours and were treated with endoscopic therapy as needed. When compared with the liberal transfusion threshold, the restrictive transfusion threshold in these bleeding patients resulted in the following:

A lower percent of patients undergoing transfusion (49 versus 86 percent) and fewer transfusions (mean 1.5 versus 3.7 units)

Fewer complications (40 versus 48 percent)

Less subsequent (further) bleeding (10 versus 16 percent; hazard ratio [HR] 0.62; 95% CI 0.43-0.91)

Fewer deaths due to uncontrolled bleeding (0.7 versus 3.1 percent)

Fewer deaths from any cause (5 versus 9 percent; HR 0.55; 95% CI 0.33-0.92)

A multicenter cluster trial that randomly assigned 936 patients with acute upper gastrointestinal bleeding to a restrictive or liberal threshold (8 g/dL versus 10 g/dL) found no significant differences in clinical outcomes; fewer transfusions were given in the restrictive group (33 versus 16 percent) [53].

These studies suggest that in patients with bleeding from other sites (eg, gynecologic, trauma) who are hemodynamically stable; who are not at increased risk for complications (eg, from unstable coronary artery disease); and who have access to rapid surgical intervention, a restrictive transfusion strategy may be safe and might be associated with improved outcomes. Randomized trials to guide transfusion practice in patients with bleeding from other sites are awaited. (See "Management of hemorrhage in gynecologic surgery".)

Non-cardiac surgery — Results of a randomized trial in patients undergoing hip surgery suggest that it is reasonable to use a lower threshold restrictive strategy of 8 g/dL for patients who have undergone surgery, in the absence of symptoms of anemia, even in older adult patients with underlying cardiovascular disease or cardiovascular risk factors.

The optimal transfusion threshold for perioperative transfusion was examined in the Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS) trial [41]. This trial randomized 2016 patients with pre-existing cardiovascular disease or cardiovascular risk factors, to liberal versus restrictive postoperative transfusion after hip repair surgery. All patients were ≥50 years (mean, 82 years) with a postoperative hemoglobin <10 g/dL. The liberal transfusion group received immediate transfusion of one unit of packed RBCs plus subsequent transfusions to raise the hemoglobin level to >10 g/dL whenever it fell below this level. The restrictive transfusion group received single unit transfusions only if they developed symptoms of anemia (defined as chest pain, orthostatic hypotension, tachycardia unresponsive to fluid resuscitation, or congestive heart failure) or, in the absence of symptoms, when the hemoglobin level fell below 8 g/dL.

The primary outcome of the study was death or an inability to walk 10 feet or across a room without assistance at the 60-day evaluation. Secondary outcomes included a combined outcome of in-hospital myocardial infarction, unstable angina, or death; and later death for any reason. Results included the following [41,54]:

The liberal and restrictive groups had similar rates of death or inability to walk 10-feet unassisted at the 60-day evaluation (35.2 versus 34.7 percent, respectively; OR 1.01; 95% CI 0.84-1.22). Similar results were found at 30-day follow-up.

The liberal and restrictive groups had similar rates of the composite endpoint of in-hospital acute coronary syndrome or death (4.3 versus 5.2 percent, respectively; OR 0.82; 99% CI 0.48-1.42).

Mortality was similar for the liberal and restrictive groups.

At 60 days, rates of death were 7.6 and 6.6 percent, respectively (OR 1.17; 99% CI 0.75-1.83).

At approximately three years, rates of death were 43 and 41 percent, respectively (HR 1.09; 95% CI 0.75-1.25).

The causes of death, and the proportion of deaths due to cardiovascular disease, cancer, and infection were comparable between the liberal and restrictive groups.

A 2018 systematic review that included this trial and nine others in patients who underwent hip or knee surgery found a higher risk of cardiovascular complications with the restrictive compared with the liberal transfusion strategy (RR 1.51; 95% CI 1.16-1.98) [55]. However, no difference was observed in mortality or other morbidity events.

Despite the results of this meta-analysis, we favor the use of the restrictive transfusion strategy based on the mortality results in the FOCUS trial.

Major intraabdominal cancer surgery resulting in a requirement for care in the intensive care unit is a possible exception based on the results of one small clinical trial [56]; however, we do not use liberal transfusion in these patients and await additional trials. (See 'Intensive care unit/septic shock' above.)

Issues related to autologous blood salvage and reinfusion during surgery are discussed separately. (See "Surgical blood conservation: Blood salvage".)

Cardiac surgery — Transfusion thresholds in cardiac surgery have been evaluated in multiple randomized trials. A 2018 meta-analysis of data from these trials suggested that a restrictive transfusion strategy with a hemoglobin threshold of 7.5 to 8 g/dL appears to be reasonable in patients undergoing cardiac surgery with cardiopulmonary bypass [22]. A restrictive threshold (hemoglobin of 7.5 to 8 g/dL; hematocrit above 21 to 24 percent) is also supported by the following trials:

The largest clinical trial conducted is the Transfusion Requirements in Cardiac Surgery III (TRICS III) trial, which randomly assigned 5243 patients undergoing cardiac surgery with cardiopulmonary bypass to transfusion for a hemoglobin of <7.5 g/dL versus a higher level (<8.5 g/dL if on the non-ICU ward or <9.5 g/dL if in the operating room or ICU) [25]. Approximately 60 percent had good left ventricular function; the procedures included coronary artery bypass grafting (CABG), valve surgery, or both. The incidence of a composite endpoint of death, non-fatal myocardial infarction, stroke, or renal failure with dialysis was similar in the restrictive and liberal groups (12.3 versus 12.9 percent; odds ratio [OR] 0.95; 95% CI -2.38-1.27). Mortality was also similar (3.0 versus 3.6 percent; OR 0.85; 95% CI 0.62-1.16). Fewer people in the restrictive group received transfusions (52 versus 73 percent) and people who were transfused received fewer units of blood (2 versus 3 units). Six months after surgery, the two different transfusion thresholds showed no significant difference in mortality or morbidities (those included in the primary outcome and others) [57].

The Transfusion Indication Threshold Reduction (TITRe2) trial randomly assigned 2007 patients who underwent cardiac surgery to postoperative transfusion for a hemoglobin threshold of <7.5 g/dL versus <9 g/dL [58]. Approximately two-thirds of the patients had underlying coronary artery disease, and the procedures included CABG, valve surgery, or both. The incidence of a composite endpoint of infection or an ischemic event was similar in the restrictive and liberal groups (35 versus 33 percent). In secondary analyses, there were more deaths at 90 days in the restrictive group (4.2 versus 2.6 percent); however, the 30 day mortality was similar (2.6 versus 1.9 percent) as was the incidence of pulmonary complications (13 versus 12 percent). Transfusions were significantly reduced with the restrictive strategy (median 1 versus 2 units per patient; transfusion avoided in 36 versus 5 percent); and transfusion costs were lower with restrictive transfusion.

Another trial randomly assigned 428 consecutive patients undergoing CABG to postoperative transfusion at a hemoglobin <8 g/dL versus <9 g/dL [59]. There was no difference in morbidity, mortality, or self-assessment for fatigue or anemia between the two groups. Postoperative transfusion rates were significantly lower for the group with the lower transfusion threshold (0.9 versus 1.4 RBC units/patient), amounting to a savings of 500 RBC units per 1000 CABG procedures.

A fourth trial randomly assigned 502 consecutive patients who underwent cardiac surgery with cardiopulmonary bypass to a liberal or restrictive transfusion strategy (to maintain hematocrit at 30 or 24 percent respectively) throughout surgery and the postoperative period (Transfusion Requirements After Cardiac Surgery; TRACS) [60]. The primary outcome was a composite endpoint of 30-day all-cause mortality, cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration. There was no difference in this composite endpoint between the groups (10 percent liberal versus 11 percent restrictive). Independent of transfusion strategy, the number of transfusions correlated with clinical complications and death (HR 1.2 for each unit transfused).

A fifth trial randomly assigned 722 cardiac surgery patients to liberal or restrictive transfusion threshold (hematocrit of 28 or 24 percent) and found no differences in a composite endpoint of postoperative in-hospital morbidity and mortality [61].

Four trials enrolling over 7000 patients undergoing cardiac surgery reported 30-day mortality [25,58,60,62]. The 2018 meta-analysis found the risk ratio for 30-day mortality for a restrictive compared with a liberal transfusion strategy was 0.99; 95% CI 0.74-1.33 [22].

This issue is discussed in more detail separately. (See "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Blood transfusion'.)

Chronic kidney disease — Management of anemia in patients with chronic kidney disease is complex. Discussion of transfusion and alternatives to transfusion (eg, erythropoietin, iron) in this setting are presented separately. (See "Treatment of anemia in dialysis patients" and "Kidney transplantation in adults: Anemia and the kidney transplant recipient", section on 'Treatment' and "Treatment of iron deficiency in nondialysis chronic kidney disease (CKD) patients".)

Ambulatory patient — Symptoms from chronic anemia in ambulatory (ie, non-hospitalized) patients differ from those caused by acute decreases in hemoglobin concentration in hospitalized patients, because there is time for compensatory mechanisms to occur. The optimal transfusion threshold in ambulatory patients has not been studied.

Some patients with chronic anemia (eg, from bone marrow failure syndromes) may be dependent upon RBC replacement over a period of months or years, which can lead to iron overload. Approximately 200 mg of iron are delivered per unit of RBC; this iron is released when hemoglobin from the transfused RBCs is metabolized after red cell death. Chelating therapy is recommended after transfusion of approximately 10 to 20 red cell units in patients who are anticipated to require ongoing red cell transfusion support [15]. (See "Approach to the patient with suspected iron overload", section on 'Transfusional iron overload'.)

RBC transfusion in patients with acquired or congenital hemolytic anemia is more complex, because transfusion also suppresses erythropoiesis. This issue is discussed separately. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques" and "Warm autoimmune hemolytic anemia (AIHA) in adults", section on 'Stabilization and transfusion for severe anemia'.)

Erythropoietin treatment may be an alternative to chronic transfusion for some ambulatory patients. (See "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer" and "Treatment of anemia in nondialysis chronic kidney disease" and "Hyporesponse to erythropoiesis-stimulating agents (ESAs) in chronic kidney disease" and "Surgical blood conservation: Preoperative autologous blood donation", section on 'Role of erythropoietin'.)

Oncology patient — There are two major groups of oncology patients for whom transfusion may be indicated:

Patients undergoing myelosuppressive chemotherapy

Patients with terminal cancer receiving palliative care

The approach to blood transfusion may differ for these groups depending on the goals of therapy.

In treatment — Two small trials (combined sample size of 149 patients) have compared transfusion thresholds in patients undergoing cancer therapy for hematologic malignancies [63,64]. Pending adequately powered trials, patients undergoing cancer therapy with curative intent should be transfused similarly to other medical patients, with transfusion for symptoms and consideration of transfusion at a threshold hemoglobin of 7 to 8 g/dL in the absence of symptoms. (See 'Asymptomatic hospitalized patient' above and 'Ambulatory patient' above.)

The AABB clinical practice guideline also notes that the restrictive transfusion threshold does not apply to patients with severe thrombocytopenia who are at risk of bleeding [17]. In a secondary analysis of the Platelet Dose (PLADO) trial, a low hematocrit (<25 percent) was associated with increased bleeding [65]. RBCs may increase platelet responsiveness, especially in thrombocytopenic patients, and anemia has been associated with increased bleeding time [66-69].

Palliative care — Small observational studies have shown that transfusion offers symptom relief to patients with advanced cancer [70,71]. A Cochrane Database review found no randomized trials of transfusion in patients with advanced cancer, and 12 observational studies that included 653 patients [72]. These studies showed that anemic individuals had subjective responses in symptoms that ranged from 31 to 70 percent. However, receiving unnecessary transfusions takes time away from other activities. Thus, we believe the use of transfusion in oncology patients should be made on a case-by-case basis. (See "Overview of managing common non-pain symptoms in palliative care", section on 'Fatigue'.)

Patients under hospice care continue to receive treatments that improve their comfort and quality of life. Contrary to popular misconceptions, hospice care does not exclude the use of RBC transfusion to alleviate symptoms. However, the hospice model of care in the United States addresses the costs associated with transfusion differently from other benefits. Thus, patients who are benefitting from transfusion near the end of life should determine which specific benefits are available from their hospice provider. (See "Hospice: Philosophy of care and appropriate utilization in the United States", section on 'Common questions and misperceptions about hospice' and "Hospice: Philosophy of care and appropriate utilization in the United States", section on 'Limitations'.)

HOSPITAL-WIDE OVERSIGHT PROGRAMS/PATIENT BLOOD MANAGEMENT — Many hospitals have developed general guidelines for the appropriate use of blood transfusion, and an "implementation blueprint" for establishing a patient blood management (PBM) program has been published by members of the High Value Practice Academic Alliance [73].

PBM programs and broad guidelines should not supersede clinical judgment in decisions regarding transfusion, especially by clinicians who are familiar with the individual patient. As an example, if a patient is experiencing symptoms that are known to reflect cardiac ischemia in that individual, transfusion may be appropriate. Conversely, if a patient is known to tolerate a lower hemoglobin than specified in the guideline, it may be possible for that patient to avoid transfusion.

Reducing the need for transfusions — A PBM program uses "an evidence-based multidisciplinary approach to optimizing the care of patients who might need transfusion." PBM programs include interventions taken early in the preparation of medical and surgical patients for treatment, as well as techniques and strategies in the preoperative, operative, and postoperative periods or completion of treatment [74].

In an observational series involving over 400,000 adult hospital admissions over eight years (2010 to 2017), institution of a PBM program (begun in 2012) was associated with a decrease in the number of transfusions administered, from 607 per 1000 admissions to 405 per 1000 admissions, over the course of the study [75]. This corresponded to a 22 percent reduction in allogenic units transfused and a 6 percent absolute risk reduction for transfusion of any blood component, after multivariable adjustment for expected decreases over time. Some patients avoided transfusion altogether and some received fewer units. Hospital length of stay and adverse events were reduced by the end of the study period, with an estimated 15 percent reduction in length of stay beyond projected. Cost savings over the course of the program were estimated at USD $7 million. The program was phased in over several stages, sequentially targeting cardiac surgery, other surgical services, hospital nurses, and medical services, with institution-wide education, decision-support, and data infrastructure. Focused efforts continued with smaller groups and enhanced hemovigilance.

Three pillars of this type of program include optimizing hematopoiesis, minimizing blood loss and bleeding, and harnessing and optimizing tolerance or treatment of anemia [76].

Two components of PBM that offer the opportunity to reduce blood use are:

Since preoperative anemia is strongly associated with increased risk of transfusion in surgical patients, it is important to screen for anemia early enough prior to surgery to have time to evaluate the cause of anemia and treat it if possible [77].

Use of a restrictive transfusion approach reduces blood transfusion for those who do not need it.

In addition, other techniques that may reduce blood use include stopping drugs that impair hemostasis (ie, aspirin) when possible, and using meticulous surgical technique.

We are in favor of such programs because they attempt to reduce unnecessary transfusion and may reduce transfusion-related adverse events and/or costs [78]. Our approach is consistent with the conditional recommendations from an International Consensus Panel, which were in favor of the implementation of PBM programs to improve appropriate use of RBC transfusions, along with adoption of computerized or electronic decision support systems [30].

Strategies to reduce the need for transfusions in surgical patients are discussed in more detail separately. (See "Perioperative blood management: Strategies to minimize transfusions".)

Extending the blood supply — PBM programs are especially important during times of blood shortages, such as is anticipated during the 2019 coronavirus disease (COVID-19) pandemic. Early reports from the pandemic have indicated significant reductions in inventories (eg, due to stay-at-home practices [social distancing] and cancellation of thousands of blood drives) [79,80].

Several measures have been taken to extend the blood supply during the COVID-19 pandemic; these include:

Consider using RhD-negative blood for women of childbearing age and individuals who have anti-D antibodies.

Consider using type A plasma for massive transfusions.

Consider developing strategies for resource-limited situations and contingency plans for shortages.

Consider use of perioperative blood salvage.

Consider crossmatching units of blood for two patients rather than reserving them for a single patient.

Consider lowering transfusion triggers.

The US Food and Drug Administration (FDA) has revised donor deferral criteria to increase the donor pool. (See "Blood donor screening: Medical history", section on 'COVID-19 pandemic considerations'.)

Many groups have called for healthy individuals to donate blood. There are several resources for determining available sites for donation, including:

Community blood centers

The American Red Cross (www.redcrossblood.org or 1-800-733-2767)

The AABB (www.aabb.org or 301-907-6977)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anemia in adults" and "Society guideline links: Transfusion and patient blood management".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: When your cancer treatment makes you tired (The Basics)" and "Patient education: Blood donation (giving blood) (The Basics)")

Beyond the Basics topics (see "Patient education: Blood donation and transfusion (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Cause of anemia – Anemia is associated with adverse clinical outcomes. Transfusion is only a short-term treatment for anemia, and decisions about transfusions should be based on data from randomized trials. It is essential to evaluate and treat, when possible, the underlying cause of anemia. (See 'Rationale for transfusion' above.)

Evidence for restrictive strategy – Restrictive transfusion strategies refer to those that transfuse at a lower hemoglobin concentration (7 to 8 g/dL), in comparison to liberal transfusion strategies, which transfuse at higher hemoglobin concentrations (table 2). There is excellent clinical trial evidence that supports use of a restrictive strategy to guide transfusion decisions in most patients. Transfusion thresholds that restrict transfusion in this way are safe in most patient populations (figure 1) and will reduce unnecessary transfusions. (See 'Rationale for transfusion' above and 'Overview of our approach' above.)

Clinical context – All patients should be assessed clinically when transfusion is considered. If the patient is stable, transfusion may not be needed even when the hemoglobin level is 7 to 8 g/dL. (See 'Symptomatic patient' above.)

Indications for restrictive strategy – For most medical and surgical hospitalized hemodynamically stable patients, including those in the intensive care unit or with septic shock, we recommend using a restrictive transfusion strategy rather than a liberal strategy (Grade 1B). Details are summarized in the figure (algorithm 1).

This applies to individuals with underlying cardiovascular disease undergoing orthopedic surgery or cardiac surgery, ambulatory patients, and individuals with gastrointestinal bleeding who are hemodynamically stable. In most cases, we maintain a hemoglobin ≥7 to 8 g/dL rather than >10 g/dL.

We base thresholds for specific populations on values determined to be safe in clinical trials that most closely resemble the patient; these are summarized in the table (table 2). In some cases, an individual may be asymptomatic at a hemoglobin of 7 to 8 g/dL, and clinician judgment may support not administering a transfusion in those cases. (See 'Thresholds for specific patient populations' above and 'Intensive care unit/septic shock' above and 'Asymptomatic hospitalized patient' above and 'Ambulatory patient' above.)

Exceptions – Exceptions include the following:

Symptoms – Symptomatic patients with hemoglobin <10 g/dL should be transfused to improve hemodynamic instability and symptoms of myocardial ischemia. (See 'Symptomatic patient' above.)

ACS/MI – For patients with acute coronary syndromes (ACS, including acute myocardial infarction [MI]), we use an individualized approach. We transfuse when the hemoglobin is ≤8 g/dL; we consider transfusion when the hemoglobin is between 8 and 10 g/dL; and we maintain the hemoglobin ≥10 g/dL in the patient with symptoms, hemodynamic instability, or ongoing ischemia. In a stable, asymptomatic patient, it is unknown when to transfuse, although we tend to maintain a hemoglobin level >8 g/dL, which is consistent with other experts, including other UpToDate authors. (See 'Acute coronary syndrome (including MI)' above and "Overview of the non-acute management of ST elevation myocardial infarction", section on 'Red cell transfusion' and "Overview of the non-acute management of unstable angina and non-ST elevation myocardial infarction", section on 'Red cell transfusion'.)

Massive transfusion – Patients requiring massive transfusion (eg, from trauma or ongoing bleeding) often cannot be managed using hemoglobin thresholds. This issue is discussed separately. (See "Massive blood transfusion" and "Initial management of moderate to severe hemorrhage in the adult trauma patient".)

Chronic transfusion-dependence – Chronic transfusion-dependent anemia, such as in transfusion-dependent thalassemia, generally require a different approach. (See "Management of thalassemia", section on 'Regular transfusions'.)

Palliative care – Transfusion may be appropriate in the palliative setting. Some hospice programs provide blood transfusion for comfort and symptom relief. (See 'Palliative care' above.)

Number of units – Transfusion of one unit of red blood cells (RBCs) at a time is reasonable for hemodynamically stable patients, with assessment of symptoms immediately after transfusion and post-transfusion hemoglobin levels, which can be done as early as 15 minutes after transfusion. (See 'Thresholds for specific patient populations' above.)

PBM – Hospital-wide patient blood management (PBM) programs may be helpful in guiding transfusion practices and reducing unnecessary transfusions, but they should not supersede clinical judgment. (See 'Hospital-wide oversight programs/patient blood management' above.)

Adverse events – Risks and complications of transfusion are discussed in separate topic reviews listed above. (See 'Risks and complications of transfusion' above.)

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  63. Webert KE, Cook RJ, Couban S, et al. A multicenter pilot-randomized controlled trial of the feasibility of an augmented red blood cell transfusion strategy for patients treated with induction chemotherapy for acute leukemia or stem cell transplantation. Transfusion 2008; 48:81.
  64. DeZern AE, Williams K, Zahurak M, et al. Red blood cell transfusion triggers in acute leukemia: a randomized pilot study. Transfusion 2016; 56:1750.
  65. Uhl L, Assmann SF, Hamza TH, et al. Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial. Blood 2017; 130:1247.
  66. Valles J, Santos MT, Aznar J, et al. Erythrocytes metabolically enhance collagen-induced platelet responsiveness via increased thromboxane production, adenosine diphosphate release, and recruitment. Blood 1991; 78:154.
  67. Escolar G, Garrido M, Mazzara R, et al. Experimental basis for the use of red cell transfusion in the management of anemic-thrombocytopenic patients. Transfusion 1988; 28:406.
  68. Blajchman MA, Bordin JO, Bardossy L, Heddle NM. The contribution of the haematocrit to thrombocytopenic bleeding in experimental animals. Br J Haematol 1994; 86:347.
  69. Valeri CR, Cassidy G, Pivacek LE, et al. Anemia-induced increase in the bleeding time: implications for treatment of nonsurgical blood loss. Transfusion 2001; 41:977.
  70. Gleeson C, Spencer D. Blood transfusion and its benefits in palliative care. Palliat Med 1995; 9:307.
  71. Sciortino AD, Carlton DC, Axelrod A, et al. The efficacy of administering blood transfusions at home to terminally ill cancer patients. J Palliat Care 1993; 9:14.
  72. Preston NJ, Hurlow A, Brine J, Bennett MI. Blood transfusions for anaemia in patients with advanced cancer. Cochrane Database Syst Rev 2012; :CD009007.
  73. Sadana D, Pratzer A, Scher LJ, et al. Promoting High-Value Practice by Reducing Unnecessary Transfusions With a Patient Blood Management Program. JAMA Intern Med 2018; 178:116.
  74. https://www.aabb.org/news-resources/resources/patient-blood-management (Accessed on May 14, 2021).
  75. Warner MA, Schulte PJ, Hanson AC, et al. Implementation of a Comprehensive Patient Blood Management Program for Hospitalized Patients at a Large United States Medical Center. Mayo Clin Proc 2021; 96:2980.
  76. Shander A, Van Aken H, Colomina MJ, et al. Patient blood management in Europe. Br J Anaesth 2012; 109:55.
  77. Gombotz H, Rehak PH, Shander A, Hofmann A. Blood use in elective surgery: the Austrian benchmark study. Transfusion 2007; 47:1468.
  78. Mehra T, Seifert B, Bravo-Reiter S, et al. Implementation of a patient blood management monitoring and feedback program significantly reduces transfusions and costs. Transfusion 2015; 55:2807.
  79. Shander A, Goobie SM, Warner MA, et al. Essential Role of Patient Blood Management in a Pandemic: A Call for Action. Anesth Analg 2020; 131:74.
  80. Pagano MB, Hess JR, Tsang HC, et al. Prepare to adapt: blood supply and transfusion support during the first 2 weeks of the 2019 novel coronavirus (COVID-19) pandemic affecting Washington State. Transfusion 2020; 60:908.
Topic 7948 Version 75.0

References

1 : Red blood cell transfusion in the treatment and management of anaemia: the search for the elusive transfusion trigger.

2 : Consensus conference. Perioperative red blood cell transfusion.

3 : Human cardiovascular and metabolic response to acute, severe isovolemic anemia.

4 : Heart rate increases linearly in response to acute isovolemic anemia.

5 : Acute severe isovolemic anemia impairs cognitive function and memory in humans.

6 : The Effects of red Blood Cell Transfusion on Tissue Oxygenation and the Microcirculation in the Intensive Care Unit: A Systematic Review.

7 : Effect of anaemia and cardiovascular disease on surgical mortality and morbidity.

8 : Mortality and morbidity in patients with very low postoperative Hb levels who decline blood transfusion.

9 : An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion (CME).

10 : Time course and etiology of death in patients with severe anemia.

11 : Preoperative hematocrit levels and postoperative outcomes in older patients undergoing noncardiac surgery.

12 : Characteristics and in-hospital outcomes of patients with non-ST-segment elevation myocardial infarction undergoing an invasive strategy according to hemoglobin levels.

13 : Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.

14 : Long-Term Outcomes Among Patients Discharged From the Hospital With Moderate Anemia: A Retrospective Cohort Study.

15 : Iron-chelating therapy for transfusional iron overload.

16 : From Tolerating Anemia to Treating Anemia.

17 : Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage.

18 : Early changes in hemoglobin and hematocrit levels after packed red cell transfusion in patients with acute anemia.

19 : Equilibration of hemoglobin concentration after transfusion in medical inpatients not actively bleeding.

20 : Red blood cell transfusion: a clinical practice guideline from the AABB*.

21 : A single unit transfusion policy reduces red cell transfusions in general medical in-patients.

22 : Clinical trials evaluating red blood cell transfusion thresholds: An updated systematic review and with additional focus on patients with cardiovascular disease.

23 : Restrictive versus Liberal Transfusion Strategy in the Perioperative and Acute Care Settings: A Context-specific Systematic Review and Meta-analysis of Randomized Controlled Trials.

24 : Outcomes of restrictive versus liberal transfusion strategies in older adults from nine randomised controlled trials: a systematic review and meta-analysis.

25 : Restrictive or liberal red-cell transfusion for cardiac surgery.

26 : Decreased red blood cell use and mortality in hospitalized patients.

27 : Trends in red blood cell transfusion and 30-day mortality among hospitalized patients.

28 : Impact of more restrictive blood transfusion strategies on clinical outcomes: a meta-analysis and systematic review.

29 : Should we universally adopt a restrictive approach to blood transfusion? It's all about the number.

30 : Patient Blood Management: Recommendations From the 2018 Frankfurt Consensus Conference.

31 : Patient Blood Management: Recommendations From the 2018 Frankfurt Consensus Conference.

32 : Practice guidelines for perioperative blood management: an updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Management*.

33 : Guidelines for the diagnosis and management of adult myelodysplastic syndromes.

34 : Guidelines for the diagnosis and management of adult myelodysplastic syndromes.

35 : Treatment of anemia in patients with heart disease: a clinical practice guideline from the American College of Physicians.

36 : Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012.

37 : Guidelines on the management of anaemia and red cell transfusion in adult critically ill patients.

38 : Guidelines on the management of anaemia and red cell transfusion in adult critically ill patients.

39 : Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease

40 : Indications for and Adverse Effects of Red-Cell Transfusion.

41 : Liberal or restrictive transfusion in high-risk patients after hip surgery.

42 : Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease.

43 : Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Clinical Trial.

44 : Conservative versus liberal red cell transfusion in acute myocardial infarction (the CRIT Randomized Pilot Study).

45 : Treatment of anemia in patients with heart disease: A systematic review.

46 : Patterns and outcomes of red blood cell transfusion in patients undergoing percutaneous coronary intervention.

47 : Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting: systematic review and meta-analysis.

48 : A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group.

49 : Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases?

50 : Lower versus higher hemoglobin threshold for transfusion in septic shock.

51 : Transfusion threshold of 7 g per deciliter--the new normal.

52 : Transfusion strategies for acute upper gastrointestinal bleeding.

53 : Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial.

54 : Liberal versus restrictive blood transfusion strategy: 3-year survival and cause of death results from the FOCUS randomised controlled trial.

55 : Restrictive Versus Liberal Strategy for Red Blood-Cell Transfusion: A Systematic Review and Meta-Analysis in Orthopaedic Patients.

56 : Transfusion requirements in surgical oncology patients: a prospective, randomized controlled trial.

57 : Six-Month Outcomes after Restrictive or Liberal Transfusion for Cardiac Surgery.

58 : Liberal or restrictive transfusion after cardiac surgery.

59 : Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome.

60 : Transfusion requirements after cardiac surgery: The TRACS randomized controlled trial.

61 : A randomized clinical trial of red blood cell transfusion triggers in cardiac surgery.

62 : Transfusion Threshold of Hemoglobin 80 g/L Is Comparable to 100 g/L in Terms of Bleeding in Cardiac Surgery: A Prospective Randomized Study.

63 : A multicenter pilot-randomized controlled trial of the feasibility of an augmented red blood cell transfusion strategy for patients treated with induction chemotherapy for acute leukemia or stem cell transplantation.

64 : Red blood cell transfusion triggers in acute leukemia: a randomized pilot study.

65 : Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial.

66 : Erythrocytes metabolically enhance collagen-induced platelet responsiveness via increased thromboxane production, adenosine diphosphate release, and recruitment.

67 : Experimental basis for the use of red cell transfusion in the management of anemic-thrombocytopenic patients.

68 : The contribution of the haematocrit to thrombocytopenic bleeding in experimental animals.

69 : Anemia-induced increase in the bleeding time: implications for treatment of nonsurgical blood loss.

70 : Blood transfusion and its benefits in palliative care.

71 : The efficacy of administering blood transfusions at home to terminally ill cancer patients.

72 : Blood transfusions for anaemia in patients with advanced cancer.

73 : Promoting High-Value Practice by Reducing Unnecessary Transfusions With a Patient Blood Management Program.

74 : Promoting High-Value Practice by Reducing Unnecessary Transfusions With a Patient Blood Management Program.

75 : Implementation of a Comprehensive Patient Blood Management Program for Hospitalized Patients at a Large United States Medical Center.

76 : Patient blood management in Europe.

77 : Blood use in elective surgery: the Austrian benchmark study.

78 : Implementation of a patient blood management monitoring and feedback program significantly reduces transfusions and costs.

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

80 : Prepare to adapt: blood supply and transfusion support during the first 2 weeks of the 2019 novel coronavirus (COVID-19) pandemic affecting Washington State.