Indications and hemoglobin thresholds for RBC transfusion in adults

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 >10 g/dL (100 g/L) and a hematocrit >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 35 years, a large body of clinical evidence has been generated, resulting in the publication of many guidelines for RBC transfusion in different settings. (See 'Review of guidelines' below.)

Over these years, a large number of randomized trials have been performed in different patient populations, allowing for guidelines to be based on prospective clinical trial data rather than on observational data. A common theme of these transfusion threshold 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.

This topic reviews indications and thresholds for RBC transfusion in adults. Separate topics discuss indications and thresholds for other populations and other aspects of transfusion:

●Newborns – (See "Red blood cell (RBC) transfusions in the neonate".)

●Children – (See "Red blood cell transfusion in infants and children: Indications".)

●Surgery – (See "Intraoperative transfusion and administration of clotting factors", section on 'Red blood cells'.)

●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".)

●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".)

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:

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.

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, since 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]. 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 routine 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 >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:

●Infection – Infection is a risk of transfusion since certain 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 2021 meta-analysis of randomized trials did not find an increased risk of such infection [13]. (See "Blood donor screening: Medical history", section on 'Screening for infectious risks' and "Blood donor screening: Laboratory testing", section on 'Infectious disease screening and surveillance'.)

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

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

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

●Iron overload – This typically 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 and expanded in several topics included with the overview. (See "Diagnostic approach to anemia in adults".)

Although the hemoglobin threshold chosen as a transfusion trigger is based on results from clinical trials, we emphasize that clinical judgment as to when to transfuse each particular patient 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, comorbidities, 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.

Our approach is consistent with that used in the 2023 Association for the Advancement of Blood & Biotherapies (AABB) Red Blood Cell Transfusion International Guidelines, which one of us coauthored [17,18]. These 2023 AABB Guidelines revise and augment prior AABB Guidelines that were published in 2012 and 2016 [18,19]. (See 'Review of guidelines' below.)

Restrictive transfusion strategy for most stable patients — For most hemodynamically stable medical and surgical patients, with the exception of patients with acute myocardial infarction (see 'Acute MI' below), we recommend using a restrictive transfusion strategy (giving less blood; transfusing at a lower hemoglobin level [typically 7 to 8 g/dL]; 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 (table 2). The specific threshold is based on the value established as safe in the clinical trial with the population that most closely resembles the patient. (Related Pathway(s): Anemia: Indications for red blood cell transfusion in hospitalized adults.)

Some patients will remain asymptomatic from anemia at hemoglobin values that are lower than our recommended threshold; conversely, transfusion at a higher hemoglobin level is often appropriate for symptomatic patients (see 'Symptomatic patient' below). In addition, threshold-based transfusion generally is not appropriate for patients requiring massive transfusion. The final decision regarding transfusion must take into account the patient's wishes and clinical status.

Major exceptions to the use of a threshold of 7 to 8 g/dL include:

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

●Patients with acute MI require higher thresholds for transfusion. (See 'Acute 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".)

●Different values, reflecting differing roles of transfusion, are used for chronic transfusion-dependent anemias such as sickle cell disease or thalassemia. (See "Management of thalassemia", section on 'Regular transfusions'.)

One unit at a time — 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 [19,20]. Whenever possible, we also initiate or continue treatment of the underlying condition responsible for the anemia. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Administering the transfusion'.)

Assessment of the post-transfusion hemoglobin 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 [21,22].

Summary of supporting evidence — Our approach of considering a threshold hemoglobin of 7 or 8 g/dL for most hemodynamically stable medical and surgical patients is based on the most comprehensive evidence, which comes from a 2021 systematic review and meta-analysis (Cochrane review) of 48 randomized clinical trials comparing higher versus lower transfusion thresholds in 21,433 medical and surgical patients (adults and children) [23].

Evidence for acute myocardial infarction (acute MI) from 2023 is discussed below. (See 'Acute MI' below.)

Trials were included in the 2021 meta-analysis 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 [23]. 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 0.99, 95% CI 0.86-1.15) (figure 1)

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

●No increased risk of myocardial infarction (RR 1.04, 95% CI 0.87-1.24)

●No difference in congestive heart failure (RR 0.83, 95% CI 0.53-1.29

●No difference in stroke (RR 0.84, 95% CI 0.64-1.09)

●No difference in rebleeding (RR 0.80, 95% CI 0.59-1.09)

●No difference in thromboembolism (RR 1.11, 95% CI 0.65-1.88)

Although other meta-analyses on transfusion thresholds have been published [24,25], we have based our transfusion recommendations primarily on the 2021 meta-analysis cited above because it contains the most extensive and most recent available data and because it follows a strict methodology for conducting such systematic analyses [23].

The 2021 meta-analysis also examined subgroups of patients enrolled in trials. As in the overall analysis, compared with liberal transfusion strategies, restrictive transfusion was shown to have a similar 30-day mortality in four patient subgroups:

●Cardiac surgery – Four trials conducted in 7411 patients undergoing cardiac surgery (RR for 30-day mortality 0.99, 95% CI 0.74-1.33).

●Orthopedic Surgery – Eight trials in 3111 participants (RR for 30-day mortality 1.16, 95% CI 0.75-1.79).

●Vascular surgery – Two trials in 157 participants (RR 0.98, 95% CI 0.30-3.25).

●Critical care – Nine trials in 3529 participants receiving critical care for assorted reasons (RR 1.06, 95% CI 0.85-1.32).

There was one subgroup in which mortality differed between subgroups:

●Acute blood loss or trauma – Three trials in 1522 participants showed that mortality was significantly lower when a restrictive strategy rather than a liberal strategy was used (RR for 30-day mortality 0.65, 95% CI 0.43- 0.97). (See "Initial management of moderate to severe hemorrhage in the adult trauma patient", section on 'Resuscitation and transfusion'.)

For hematologic malignancies, the data were not conclusive due to very wide confidence intervals. Two small trials in 149 participants showed a RR for 30-day mortality of 0.37, 95% CI 0.07-1.95. (See 'During cancer treatment' below.)

Evidence from a large cohort of hospitalized patients from 2014 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 <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 rather than a liberal 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 this hospital system 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].

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]. However, we recognize that others may favor using the restrictive threshold of 7 g/dL across various populations. (See 'Review of guidelines' below.)

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 preexisting coronary artery disease may provide better oxygen delivery to a vulnerable myocardium. In contrast, 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 not in the ICU is based solely on the values used in randomized trials; we do not know if these two populations (ICU and medical/surgical) are biologically or physiologically distinct and truly have different hemoglobin requirements.

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

Review of guidelines — Transfusion guidelines have been published since 2016 by the following societies:

●Association for the Advancement of Blood & Biotherapies (AABB), 2023 [17].

This was developed in collaboration with and endorsed by the International Society of Blood Transfusion, International Collaboration for Transfusion Medicine Guidelines, the Society of Critical Care Medicine, the European Blood Alliance, and the Society for the Advancement of Patient Blood Management.

●Society of Thoracic Surgeons (STS), Society of Cardiovascular Anesthesiologists (SCA), American Society of ExtraCorporeal Technology (AmSECT), and the Society for the Advancement of Blood Management (SABM), 2021 [30].

●Society of Cardiovascular Anesthesiologists, 2019 [31].

●International (Frankfurt) Consensus Conference on patient blood management, 2018 [32].

●United Kingdom National Clinical Guideline Centre, 2016 [33].

In general, the different guidelines have recommended use of a restrictive transfusion threshold of 7 to 8 g/dL. 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.

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

THRESHOLDS FOR SPECIFIC PATIENT POPULATIONS — The table summarizes the data for specific patient populations (table 2).

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 [34,35]. 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 such as 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".)

Transfusion in patients with acute myocardial infarction (acute MI) is discussed below. (See 'Acute MI' below.)

Intraoperative — (See "Intraoperative transfusion and administration of clotting factors", section on 'Red blood cells'.)

Acute and chronic cardiovascular disease — The decision of whether to transfuse patients with cardiovascular disease should consider the nature of the cardiovascular disorder. Patients with acute MI require different thresholds than patients with stable coronary artery disease or congestive heart failure.

Acute MI — In acute MI, clinical trial evidence demonstrates improved outcomes with liberal transfusion. This differs from other settings including chronic cardiovascular disease. We generally maintain the hemoglobin ≥10 g/dL in most MI patients, although we would accept lower hemoglobin levels in patients who were stable and asymptomatic. Unlike other critical care patients, in acute MI we do not advise a restrictive transfusion strategy of 7 to 8 g/dL.

The following evidence supports using a liberal transfusion strategy in patients with acute MI.

●MINT trial – MINT (Myocardial Ischemia and Transfusion) randomly assigned 3504 individuals (mean age, 72 years) with acute MI and hemoglobin <10 g/dL to receive transfusion for hemoglobin <7 or 8 g/dL (restrictive) or for hemoglobin <10 g/dL (liberal) [36].

•The composite outcome (death or recurrent MI) occurred more commonly in the restrictive group; statistical significance was borderline (16.9 versus 14.5 percent; RR 1.15, 95% CI 0.99-1.34).

•There was a trend towards higher all-cause mortality in the restrictive group that did not reach statistical significance (9.9 versus 8.3 percent; relative risk [RR] 1.19, 95% CI 0.96-1.47) and a trend towards greater chance of recurrent MI in the restrictive group that did not reach statistical significance (8.5 versus 7.2 percent; RR 1.19, 95% CI 0.94-1.49).

•Cardiovascular death occurred more commonly in the restrictive transfusion group (5.5 versus 3.2 percent; RR 1.74, 95% CI 1.26-2.40). Rates of adverse events (heart failure, stroke, venous thromboembolism, and pneumonia/bacteremia) were similar in both groups.

Thus, the trial results suggest that a liberal transfusion strategy has the potential for clinical benefit with an acceptable risk of harm [37].

●REALITY and other trials – A meta-analysis of three trials (820 patients) published before MINT did not find a difference in 30 day all-cause mortality with restrictive versus liberal transfusion (RR 1.61, 95% CI 0.38-6.88) [23]. In the largest of these trials (REALITY), which 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 restrictive group showed a trend towards a lower risk of major adverse cardiac events (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 0.00-1.17) [38]. However, analysis of survivors at 30 days who were then followed for one year found that major cardiac events were more frequent in the restrictive group (hazard ratio [HR] 1.44, 95% CI 1.01-2.03) [39].

Transfusion in patients undergoing PCI complicated by periprocedural bleeding is discussed separately. (See "Periprocedural bleeding in patients undergoing percutaneous coronary intervention", section on 'Blood transfusion'.)

Preexisting coronary artery disease — Trials have not been designed to specifically address patients with preexisting coronary artery disease; high quality evidence to evaluate transfusion thresholds is lacking.

Data taken from two randomized trials that included patients with coronary artery disease (Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair [FOCUS] and Transfusion Requirements in Critical Care [TRICC]) showed that, although cardiac events were numerically higher in the restrictive transfusion arm, the results were not statistically different between the two transfusion thresholds [34,40]. (See 'Orthopedic surgery' below and 'Intensive care unit' below.)

These data led to previous recommendations to use a restrictive threshold of 8 g/dL. Use of this 8 g/dL threshold was somewhat challenged by a 2016 meta-analysis of selected trials that found a higher risk of ACS but not 30-day mortality among patients with cardiovascular disease who were transfused using a restrictive transfusion strategy compared with a liberal strategy [41]. However, this meta-analysis did not include all the relevant trials, and the trials that were included patients with acute MI as well as preexisting cardiovascular disease.

Given the results of the MINT trial in patients with acute MI and the absence of specific trials addressing patients with preexisting cardiac disease, we advise using a restrictive transfusion threshold of 8 g/dL, with the caveat to consider using a liberal transfusion strategy depending on the overall clinical status of the patient, extent of cardiovascular disease, presence of cardiovascular symptoms, vital signs, and patient preferences.

Transfusion of symptomatic patients with coronary artery disease is guided by the symptoms and clinical judgment, and the optimal threshold for patients with ACS is unresolved. (See 'Symptomatic patient' above.)

Heart failure — Anemia and heart failure (HF) often coexist for a variety of reasons (cytokine changes, dilutional anemia, medical therapy for HF). (See "Evaluation and management of anemia and iron deficiency in adults with heart failure", section on 'Potential causes of anemia related to heart failure'.)

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 'Cardiac surgery' below and "Evaluation and management of anemia and iron deficiency in adults with heart failure", section on 'Transfusion'.)

Cardiac surgery — Transfusion thresholds in cardiac surgery have been evaluated in multiple randomized trials. A 2021 meta-analysis of data from these trials suggested that a restrictive transfusion strategy with a hemoglobin threshold of 7.5 to 8 g/dL (hematocrit 21 to 24 percent) appears to be reasonable in patients undergoing cardiac surgery with cardiopulmonary bypass [23,42]. A restrictive threshold is supported by the following trials:

●TRICCS III – 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) [43]. 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, nonfatal myocardial infarction, stroke, or kidney 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 to 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 groups showed no significant difference in mortality or morbidities (those included in the primary outcome and others) [44].

●TITRe2 – 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 [45]. 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 [46]. 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 per patient), amounting to a savings of 500 RBC units per 1000 CABG procedures.

●TRACS – 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) [47]. 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 a restrictive or liberal transfusion threshold (hematocrit of 24 versus 28 percent) and found no differences in a composite endpoint of postoperative in-hospital morbidity and mortality [48].

Based on trials that evaluated 30-day mortality, mortality was not statistically different for a restrictive compared with a liberal transfusion strategy (risk ratio [RR] 0.99, 95% CI 0.74-1.33) [23,42].

Trauma/massive transfusion — Massive transfusion in hemodynamically unstable patients cannot be guided by hemoglobin levels alone and often cannot await interval measurements of hemoglobin. (See "Massive blood transfusion" and "Initial management of moderate to severe hemorrhage in the adult trauma patient".)

Intensive care unit — Restrictive transfusion appears to be as safe as or safer than liberal transfusion in medical patients in an intensive care unit (ICU), with the exception of patients with acute MI. (See 'Acute MI' above and "Use of blood products in the critically ill", section on 'Red blood cells'.)

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 [40]. This trial randomly assigned 838 critically ill, euvolemic patients with a hemoglobin <9 g/dL within 72 hours of admission to an ICU 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:

●Less severely ill patients (APACHE II score ≤20) – Mortality 9 percent with a restrictive threshold versus 16 percent with a liberal threshold

●Patients <55 years of age – Mortality 6 versus 13 percent

In contrast, in a subgroup analysis of 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 (0.7 versus 2.9 percent for myocardial infarction and 5.3 versus 10.7 percent for pulmonary edema).

A 2021 meta-analysis of trials in patients receiving critical care for assorted reasons (nine trials involving 3529 participants) found that outcomes were not statistically different with restrictive and liberal transfusion thresholds (RR 1.06, 95% CI 0.85-1.32) [23].

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. As there are insufficient high-quality data to evaluate transfusion thresholds in non-cardiac, non-orthopedic post-surgical ICU patients, we use the threshold of 7 g/dL for this population.

Septic shock — A hemoglobin threshold of 7 g/dL was shown to be safe in patients with septic shock in the Transfusion Requirements in Septic Shock (TRISS) trial [50]. TRISS randomly assigned 998 patients with septic shock and a hemoglobin <9 g/dL to a restrictive or a liberal transfusion strategy (transfusion at a hemoglobin ≤7g/dL or ≤9 g/dL, respectively); consensus criteria for sepsis were used (infection, systemic inflammatory response, hypotension). Transfusions were given as single units of pre-storage 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 (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'.)

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 (pulse, blood pressure), the pace of the bleeding, and the ability to stop the bleeding, rather than by the hemoglobin. (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 that have suggested 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 [51]. 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) [52].

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

Orthopedic surgery — The optimal transfusion threshold for perioperative transfusion in hip fracture repair was examined in the Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair (FOCUS) trial [34]. This is also supported by a 2021 meta-analysis that summarized eight trials in 3111 orthopedic surgery patients (RR for 30-day mortality 1.16, 95% CI 0.75-1.79 [23]. These results suggest that it is reasonable to use a restrictive strategy with a transfusion threshold of 8 g/dL for patients who have undergone surgery and do not have symptoms of anemia, including in older adults with underlying cardiovascular disease or cardiovascular risk factors.

The FOCUS trial randomly assigned 2016 patients with pre-existing cardiovascular disease or cardiovascular risk factors, to liberal versus restrictive postoperative transfusion after hip repair surgery [34]. 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 [34,53]:

●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 ACS 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 the FOCUS trial described above and nine other trials in patients who underwent hip or knee surgery found a higher risk of cardiovascular complications (myocardial infarction, arrhythmia, angina, heart failure, cardiac arrest, other cardiovascular events) with the restrictive as compared with the liberal transfusion strategy (RR 1.51, 95% CI 1.16-1.98) [54]. However, no difference was observed in mortality or other morbidity events.

Based on the overall evidence and our view of the importance and unambiguous nature of the mortality endpoint in patients with preexisting cardiac disease, we favor the use of the restrictive transfusion strategy of 8 g/dL, though we are aware that the 2018 meta-analysis and the MINT trial results could be used to suggest the use of a liberal transfusion strategy.

Autologous blood salvage and reinfusion during surgery are discussed separately. (See "Surgical blood conservation: Intraoperative blood salvage".)

Chronic kidney disease — Management of anemia in patients with chronic kidney disease is complex. Discussion of transfusion and other means of increasing hemoglobin levels (erythropoietin, iron) in this setting are presented separately. (See "Treatment of anemia in patients on dialysis" and "Anemia and the kidney transplant recipient", section on 'Treatment' and "Treatment of iron deficiency in patients with nondialysis chronic kidney disease (CKD)".)

Ambulatory patient — Symptoms from anemia in ambulatory (ie, nonhospitalized) 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.

●Transient blood loss – For individuals with bleeding that has stopped and who are expected to have an adequate bone marrow response to treatment, it may be possible to avoid transfusion and use another therapy such as iron replacement. We use the same principles as in inpatients in terms of individualized decision-making and other interventions to avoid transfusion. (See "Approach to the patient who declines blood transfusion", section on 'Other interventions'.)

●Chronic anemias

•Bone marrow failure – Some patients with chronic anemia 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'.)

•Hemolytic anemias – 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".)

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.

During cancer treatment — Two small trials (combined sample size of 149 patients) have compared transfusion thresholds in patients undergoing cancer therapy for hematologic malignancies [55,56]. 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 'Restrictive transfusion strategy for most stable patients' above.)

Palliative care — There are no clinical trials in palliative care patients to guide transfusion practice. The need for RBC transfusion is determined on a case-by-case basis. When transfusions are used, careful assessment of the patient's symptoms before and after transfusion can help to determine if the patient benefited and to guide future treatment. (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'.)

Other patient groups where more data are needed — More data are needed to determine the optimal transfusion strategy in patients with the following conditions:

●Neurologic injury, stroke, and traumatic brain injury

●Other neurologic disorders

●Cancer, including hematologic malignancies

●Transfusion-dependent myelodysplastic syndromes (MDS)

●Palliative care (see 'Palliative care' above)

In the absence of data for patients with these diagnoses, we suggest determining transfusion practice based on their location of care (ICU or non-ICU) or on the similarity of their underlying disease to that of patient groups where data are available. In most cases, a hemoglobin threshold of 7 or 8 g/dL is appropriate.

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 [57].

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 [58].

In a series involving over 400,000 hospitalized adults over eight years (2010 to 2017), institution of a PBM program 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 [59]. This corresponded to a 22 percent reduction in allogenic units transfused and a 6 percent absolute risk reduction, 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 attributed to PBM. 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 [60].

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 [61].

●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 (eg, aspirin) if appropriate.

●Minimizing phlebotomies and using smaller phlebotomy volumes when possible.

●Using meticulous surgical technique.

Further details are presented separately. (See "Approach to the patient who declines blood transfusion", section on 'Minimize blood loss'.)

We are in favor of such programs because they attempt to reduce unnecessary transfusion and may reduce transfusion-related adverse events and/or costs [62]. 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 [32].

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

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 5^th to 6^th 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 10^th to 12^th 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: Blood donation (giving blood) (The Basics)" and "Patient education: Blood transfusion (The Basics)" and "Patient education: When your cancer treatment makes you tired (The Basics)")

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

SUMMARY AND RECOMMENDATIONS

●Determine 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 – There is excellent clinical trial evidence that supports use of a restrictive strategy to guide transfusion decisions in most patients, with the exception of myocardial infarction (MI). 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). 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). Some individuals may be asymptomatic at a hemoglobin of 7 to 8 g/dL, and clinician judgment may support not administering a transfusion. (See 'Thresholds for specific patient populations' above.)

●Exceptions – Exceptions to using a restrictive strategy include:

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

•Intraoperative – (See "Intraoperative transfusion and administration of clotting factors", section on 'Red blood cells'.)

•Acute MI – For patients with acute myocardial infarction (MI), we suggest a liberal transfusion strategy to maintain the hemoglobin ≥10 g/dL rather than a lower value such as 8 g/dL (Grade 2C). In a stable, asymptomatic patient, it may be reasonable to maintain a hemoglobin level close to but <10 g/dL. (See 'Acute MI' above.)

•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-dependent anemias – Chronic transfusion-dependent anemias such as sickle cell disease and transfusion-dependent thalassemia generally require a different approach. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Indications for transfusion' and "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.)

ACKNOWLEDGMENT — The UpToDate editorial staff gratefully acknowledges the extensive contributions of Arthur J Silvergleid, MD, to earlier versions of this and many other topic reviews.