Transfusion-associated circulatory overload (TACO)

INTRODUCTION — Reactions to blood component transfusion can range from mild to potentially fatal. Transfusion-associated circulatory overload (TACO) is a common transfusion reaction in which pulmonary edema develops primarily due to volume excess or circulatory overload.

TACO typically occurs in patients who receive a large volume of a transfused product over a short period of time, especially those with underlying cardiovascular or kidney disease. It is important to report suspected cases of TACO to the transfusion service as a transfusion reaction. (See 'Reporting' below.)

This topic reviews the clinical manifestations, diagnosis, management, and prevention of TACO.

A general approach to a suspected transfusion reaction, as well as other specific reactions, are presented in detail separately:

●General approach – (See "Approach to the patient with a suspected acute transfusion reaction".)

●Transfusion-related acute lung injury (TRALI) – (See "Transfusion-related acute lung injury (TRALI)".)

●Hemolytic reactions – (See "Hemolytic transfusion reactions".)

●Febrile nonhemolytic reactions (FNHTR) – (See "Immunologic transfusion reactions", section on 'Febrile nonhemolytic transfusion reactions'.)

●Immunologic/allergic reactions – (See "Immunologic transfusion reactions".)

●Sepsis – (See "Transfusion-transmitted bacterial infection".)

●Air embolism – (See "Air embolism".)

●Transfusion-associated graft-versus-host disease (ta-GVHD) – (See "Transfusion-associated graft-versus-host disease".)

●Transfusional iron overload – (See "Approach to the patient with suspected iron overload", section on 'Transfusional iron overload'.)

DEFINITION — Guidelines for the evaluation of transfusion reactions including TACO have been published by the International Society for Blood Transfusion (ISBT), the British Committee for Standards in Haematology (BCSH) of the British Society for Haematology, and the United States Centers for Disease Control and Prevention (CDC) Biovigilance Network. However, there is no uniformly accepted set of diagnostic criteria for TACO [1-3].

Most classification schemes require the development of a set of signs and symptoms to occur within 12 hours of transfusion. The ISBT and Biovigilance Network in the United States allow for symptoms up to 12 hours after the end of the transfusion [1,2]. The exact number and set of signs and symptoms varies between definitions.

Criteria from the Biovigilance Network in the United States were revised in 2021 and include the following definitions [2]:

●Definitive TACO – New onset or exacerbation of three or more of the following within 12 hours of the end of a transfusion without another explanation:

•Respiratory distress (acute or worsening)

•Evidence of pulmonary edema on examination or radiographs

•Elevated brain natriuretic protein (BNP) or N-terminal pro-hormone BNP (NT-pro BNP)

•Other unexplained cardiovascular changes (elevated central venous pressure)

●Probable TACO – Findings as above, with transfusion as a likely contributor but the individual received other fluids as well or has a history of cardiac disease that could explain the findings.

●Possible TACO – Findings as above but preexisting cardiac disease is a more likely explanation than the transfusion.

PATHOPHYSIOLOGY AND RISK FACTORS

Risk factors — TACO is a form of circulatory volume overload that can occur in any individual and with transfusion of any blood component (eg, red blood cells [RBCs], platelets, plasma components such as Fresh Frozen Plasma [FFP], Cryoprecipitate).

●Patient-related risk factors – Patient risk factors include pre-existing cardiac and possibly kidney dysfunction [4,5]. Small stature, low body weight, extremes of age (eg, <3 years, >60 years), and hypoalbuminemia have also been suggested as TACO risk factors [4-7].

The contribution of patient factors was illustrated in a 2014 retrospective Medicare database review of over 2 million transfusion admissions that included 1340 cases of TACO [6]. The following patient characteristics were associated with a greater odds ratio (OR) for TACO after adjustment for confounding variables:

•Age – OR 2.08 for age ≥85 years (compared with the reference population age 65 to 69)

•History of heart failure – OR 1.61

•Female sex – OR 1.40

•White race – OR 1.38

•History of chronic pulmonary disease – OR 1.19

●Transfusion rate and volume – The volume transfused and rate of administration correlate with the risk of TACO, making TACO less likely with Cryoprecipitate than with FFP [7]. The risk of TACO in the above study also correlated with the number of units of blood products transfused [6]:

•Two to four units – OR 2.00

•Five to nine units – OR 3.10

•More than nine units – OR 3.55

Etiology — The etiology of TACO is likely multifactorial, with the majority of patients who experience TACO often receiving large quantities of fluid prior to the transfusion (eg, hematopoietic stem cell transplant recipients). In a small study evaluating N-terminal pro-hormone BNP (NT-pro BNP), 94 percent of patients with TACO had a significantly elevated NT-pro-BNP even prior to the blood transfusion [8].

In a 2013 case-control study involving 83 patients with TACO in the medical intensive care unit (ICU), positive fluid balance, larger amount of plasma transfused, and faster blood product infusion rate were associated with an increased likelihood of TACO [7]. This informs prevention strategies including slower rates of infusion and diuresis. (See 'Prevention' below.)

In 2019, an animal model study suggested that TACO might be a "two hit" transfusion reaction, with the first hit being volume incompliance (from cardiac or kidney disease) and the second hit being a blood transfusion [9]. In the study, TACO, characterized by an increase in pulmonary hydrostatic pressure, developed only in volume-incompliant animals following RBC transfusion, not crystalloid infusion. Identifying ways in which the impact of RBCs differs from other fluids, and whether this difference holds as well for platelet and plasma components, may further elucidate TACO pathophysiology.

EPIDEMIOLOGY — The true frequency of TACO is difficult to assess due to the lack of a highly sensitive and specific clinical parameter or laboratory test. In addition, under-reporting of TACO is likely, as mild respiratory distress that resolves with diuresis may not be reported to the transfusion medicine service or blood bank [10].

Overall, TACO is estimated to occur in 1 percent or more of transfused individuals. The frequency appears to be higher in hospitalized patients, especially those in the intensive care unit (ICU).

●Any transfusions – A single-center study evaluating transfusion reaction reports found the prevalence of TACO to be 0.2 percent (102 cases of TACO in 56,208 transfused patients) [11].

●Inpatient transfusions – In the 2014 retrospective claims-based study of Medicare inpatients mentioned above (see 'Risk factors' above), the rate of TACO was 0.6 percent (1340 cases from among 2,147,038 inpatient transfusions), equivalent to an overall rate of 62.4 per 100,000 hospital stays [6].

●ICU transfusions – Rates of TACO are highest in the most acutely ill patients. In a study of TACO in a medical ICU, TACO was observed in 51 of 901 patients who received a transfusion (6 percent) [7].

●Perioperative – Perioperative series have reported rates in the range of 1 to 4 percent [12,13].

Rates of TACO do not appear to vary with the sex of the transfusion recipient, although this has not been studied rigorously and the rate was slightly higher in females than males in the study discussed above [6,14]. (See 'Pathophysiology and risk factors' above.)

TACO has been reported to be a major contributing factor in mortality from transfusion [15,16]. A study from the Serious Hazards of Transfusion (SHOT) reporting system in the United Kingdom suggests that either the incidence of TACO, or, more likely, the recognition and reporting of TACO, has been increasing over time [17]. From 2007 to 2022, reports of TACO increased steadily. In 2022 in the United Kingdom, TACO was the most common transfusion reaction associated with mortality (eight cases) and major morbidity (25 cases) [17].

Other data indicate that patients with TACO have extended lengths of stay in hospitals and intensive care units [15]. Data from the United States have demonstrated TACO to be the most common cause of death from a transfusion; in 2021, TACO accounted for 36 percent of deaths, versus 16 percent from TRALI and lower percentages from other transfusion reactions [18]. (See "Approach to the patient with a suspected acute transfusion reaction", section on 'Frequency of reactions' and "Approach to the patient with a suspected acute transfusion reaction", section on 'Mortality'.)

The under-reporting of TACO was demonstrated in an analysis that compared a retrospective review of passively reported TACO cases over an eight-year period at a tertiary hospital with a one-month active surveillance period at the same institution [19]. By passive reporting, the prevalence of TACO was 1 in 1566 plasma transfusions (0.06 percent); in comparison, by active surveillance, TACO occurred in 4 of 84 patients (4.8 percent), none of which were reported to the blood bank.

Compared with other transfusion reactions, TACO is less common than allergic and febrile nonhemolytic transfusion reactions (FNHTR) but more common than anaphylaxis, acute hemolytic transfusion reactions (AHTR), or transfusion-related acute lung injury (TRALI). In a 2014 report from Ireland, TACO accounted for 221 of 1071 serious transfusion reactions (21 percent) [20]. Other studies have found a similar proportion of transfusion reactions attributed to TACO [19]. In a 2014 report from Canada that focused exclusively on transfusion reactions associated with respiratory distress, TACO accounted for 26 of 83 reactions (31 percent) [21].

Relative frequencies of TACO and other transfusion reactions are discussed separately. (See "Approach to the patient with a suspected acute transfusion reaction", section on 'Frequency of reactions'.)

CLINICAL PRESENTATION — The possibility of TACO should be considered in any patient who has new or worsening respiratory distress during or within 12 hours of completing a transfusion [1].

The typical presentation of TACO includes respiratory distress (dyspnea, orthopnea) in a patient with known or unknown underlying heart failure who is receiving a transfusion, especially in the setting of positive fluid balance. The severity is variable, from mild dyspnea to acute respiratory decompensation. Headache is common and seizures have been reported.

Typically, symptoms occur after a significant proportion of the blood component or multiple units have been infused, up to (but usually sooner than) 12 hours following completion of the infusion.

Findings on examination may include hypoxia and/or hypertension, tachycardia, a wide pulse pressure, and/or jugular venous distension. The cardiac examination may show an S3 heart sound, and the lung examination often reveals rales and/or wheezing.

DIAGNOSTIC TESTING

Monitoring — Individuals receiving a transfusion are monitored periodically and instructed to report any concerning symptoms including respiratory distress.

Signs and symptoms include:

●Acute respiratory distress, dyspnea, or tachypnea

●Tachycardia

●Increased blood pressure

●Acute or worsening pulmonary edema

●Evidence of positive fluid balance

Additional monitoring may be appropriate in patients considered at higher than average risk of TACO (eg, in an intensive care unit, having a history of heart failure or kidney disease, older adults, those with a small blood volume, and those receiving large transfusion volumes). It may be helpful to develop local risk profile assessment tools or algorithms to use in the pre-transfusion assessment to identify high-risk patients.

Depending on the patient's risk profile, some combination or all of the following clinical parameters may be monitored:

●Blood pressure, heart rate, respiratory rate

●Pulse oximetry

●Cardiopulmonary examination for elevated jugular venous pressure, heart sounds, rales or wheezing

●Fluid balance, if fluid intake and output measurements are available

●Central venous pressure or pulmonary artery pressure, if a central venous or pulmonary artery catheter is in place

The frequency of monitoring depends on the patient's underlying condition, the number of blood components transfused, and the rapidity of infusion.

Evaluation and diagnosis — TACO should be suspected in a patient who develops respiratory distress, hypoxia, or hypertension while receiving a transfusion or in the post-transfusion period. The physical examination should focus on the cardiovascular and pulmonary examination, as well as assessment for other possible causes of dyspnea (eg, evidence of deep vein thrombosis, findings of anaphylaxis).

Due to the lack of a definitive diagnostic test, clinical judgment is required to make the diagnosis, especially since many of the patients with suspected TACO may have complex medical conditions.

In patients with signs and symptoms of TACO, oxygenation status should be assessed using pulse oximetry and/or arterial blood gas analysis, especially if pulse oximetry shows oxygenation to be low or declining. Chest imaging (usually by radiography) is likely to be helpful and should be obtained to confirm pulmonary edema and eliminate other causes of respiratory distress (eg, transfusion-related acute lung injury [TRALI], pneumothorax) [2]. Typical findings on chest radiography in TACO include pulmonary edema and in some cases cardiomegaly. Echocardiography is not routinely performed, but if done would be expected to show abnormal systolic and/or diastolic function.

Additional testing may include brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), although this is not required for diagnosis. BNP and NT-proBNP, which has a much longer half-life than BNP, are elevated in TACO and other forms of heart failure. This information may be helpful when combined with other clinical information, but by itself it is not particularly sensitive or specific for TACO (sensitivity and specificity in the 80 to 90 percent range) [8,22-24]. In selected patients, echocardiography may be helpful in determining underlying cardiac abnormalities.

Often the evaluation is focused on distinguishing TACO from TRALI, a transfusion reaction caused by immune mediators such as anti-leukocyte antibodies in the transfused component rather than the volume load. In some cases, the distinction between TACO and TRALI is relatively obvious; in others it may be difficult and require the use of multiple types of information as shown in the table (table 1). Often it is difficult to distinguish TACO from TRALI until several days after the transfusion reaction and after the response to diuretics has been evaluated. TACO and TRALI can occur simultaneously in some patients. Additional guidance on distinguishing TACO from TRALI should be sought from the transfusion medicine service or blood bank. This subject is discussed in more detail in separate topic reviews. (See "Approach to the patient with a suspected acute transfusion reaction", section on 'Respiratory distress: TACO versus TRALI' and "Transfusion-related acute lung injury (TRALI)", section on 'Differential diagnosis'.)

TACO is not known to cause fever, hives, or angioedema; patients with these symptoms should be evaluated for other transfusion reactions or medical conditions unrelated to the transfusion (table 2). (See "Approach to the patient with a suspected acute transfusion reaction".)

Treatment (see 'Management' below) should not be delayed while awaiting the results of chest radiography if the diagnosis is considered likely because many of the supportive care interventions (supplemental oxygen, ventilatory support if needed) may also be helpful for other transfusion reactions. An exception to this is the use of diuretics when it is unclear whether the patient is experiencing TACO versus TRALI, since diuresis, which is critical to the management of TACO, may not be appropriate in individuals with TRALI who have volume depletion; decisions about diuresis depend on the confidence in the diagnosis of TACO. The distinction between TACO and TRALI is discussed below. (See 'Differential diagnosis' below.)

As with all suspected transfusion reactions, suspected TACO should be reported to the transfusion service and/or blood bank. The transfusion service may provide consultation regarding the option of modifying blood components for future transfusions (eg, smaller units, volume reduction) or suggest rapid diuresis as a treatment for severe volume overload. In addition, the transfusion service may help in the evaluation of the transfusion reaction, including the distinction between TACO and TRALI if needed. (See 'Management' below.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of TACO includes other transfusion reactions and cardiopulmonary conditions.

Transfusion reactions/TRALI — Transfusion-related acute lung injury (TRALI) is the transfusion reaction most commonly considered in the differential diagnosis of TACO; however, other transfusion reactions may also cause similar symptoms. The distinction among these disorders is presented in more detail separately (table 2). (See "Approach to the patient with a suspected acute transfusion reaction".)

●TRALI – TRALI is an acute transfusion reaction characterized by respiratory distress, hypoxia, and diffuse bilateral infiltrates on chest imaging. Patients with TRALI typically become symptomatic during the transfusion or within six hours of completing the transfusion. Unlike TACO, the risk of TRALI is not related to the volume of the transfusion. TRALI may occur closer in time to the initiation of the transfusion (before significant volume is infused) and presenting features may include hypotension, fever, and transient leukopenia. TRALI is not associated with an elevated brain natriuretic peptide (BNP) or N terminal Pro-BNP (NT Pro-BNP), central venous pressure, or pulmonary artery wedge pressure. In TRALI, the ratio of protein in the edema fluid to plasma is high, reflecting an exudate rather than a transudate. A key distinguishing feature between TRALI and TACO is that TACO symptoms improve with diuresis (table 1). Thus, sometimes the diagnosis cannot be confirmed until a few days after the transfusion. (See "Transfusion-related acute lung injury (TRALI)".)

●Anaphylactic transfusion reactions – Severe allergic reactions that lead to anaphylaxis may occur in the setting of the administration of an IgA-containing blood component to an IgA-deficient individual who has pre-formed antibodies to IgA; other less common causes have also been described. Like TACO, these reactions may present with dyspnea, hypoxemia, and an abnormal lung examination. Unlike TACO, anaphylactic transfusion reactions may occur closer in time to the initiation of the transfusion (before significant volume is infused), and anaphylaxis is not associated with an elevated N terminal Pro-BNP (NT Pro-BNP), central venous pressure, or pulmonary artery wedge pressure. Anaphylactic reactions may be accompanied by stridor, hypotension, or angioedema. (See "Immunologic transfusion reactions", section on 'Anaphylactic transfusion reactions'.)

●Transfusion-associated dyspnea – Transfusion-associated dyspnea is a transfusion reaction with acute respiratory distress occurring within 24 hours of cessation of transfusion and/or that does not meet the criteria for other transfusion reactions. This entity is useful for the surveillance function of hemovigilance systems but does not have much clinical importance.

Underlying medical conditions that cause heart failure — Heart failure (HF) is a complex clinical syndrome characterized by any cardiovascular abnormality (structural or functional) in which systemic perfusion is inadequate to meet the body's metabolic demands without excessively increasing left ventricular filling pressures. HF may be caused by a number of acute and chronic conditions other than TACO, including coronary artery disease, arrhythmia, cardiomyopathy, or valvular disease. The term "flash pulmonary edema" is sometimes used to refer to a dramatic form of acute decompensated HF. (See "Determining the etiology and severity of heart failure or cardiomyopathy".)

●Like TACO, HF unrelated to the current transfusion is characterized by dyspnea and evidence of pulmonary edema.

●Unlike TACO, HF from other causes is associated with evidence of another cause and lack of a temporal association with the transfusion. TACO and HF from other causes may (and often do) coexist.

Pulmonary embolism — Pulmonary embolism (PE) is a form of venous thromboembolism with a presentation that varies widely from asymptomatic or subacute, nonspecific symptoms to acute shock and death.

●Like TACO, PE often presents with respiratory distress in a hospitalized patient.

●Unlike TACO, PE is associated with a filling defect in the pulmonary artery and typically symptoms do not resolve with diuresis.

Diagnostic evaluation for PE is presented separately (calculator 1). (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism".)

MANAGEMENT

Supportive care and diuresis — Treatment of TACO is similar to treatment of cardiogenic pulmonary edema from other causes. Once the diagnosis is strongly suspected, the transfusion should be stopped. The major interventions include fluid mobilization, supplementary oxygen, and assisted ventilation if indicated. Interventions to stabilize the patient and provide adequate oxygenation should not be delayed while performing additional evaluations or confirming the diagnosis. (See "Treatment of acute decompensated heart failure: Specific therapies".)

●Oxygen – Supplemental oxygen should be administered for individuals with hypoxemia (eg, SpO₂ <90 percent). Oxygen should be titrated to maintain adequate oxygenation while other interventions are addressed.

●Fluid mobilization – Fluid mobilization is a key component of management. Typically this is done with diuretics. An approach to diuretic dosing and additional monitoring (eg, of electrolytes and renal function) is presented separately. (See "Treatment of acute decompensated heart failure: Specific therapies", section on 'Diuretics'.)

●Ventilatory support – Assisted ventilation may be required in severe cases of TACO. Noninvasive positive pressure ventilation may be helpful in the acute management of patients with severe respiratory compromise; if this is ineffective, endotracheal intubation may be required. These subjects are discussed in separate topic reviews. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications" and "Treatment of acute decompensated heart failure: Specific therapies".)

Reporting — As with all suspected transfusion reactions, TACO should be reported to the transfusion medicine service and/or blood bank. This is important both for preventing future reactions in that patient, as well as for hospital-wide and population-wide quality control and procedures, including record keeping, hemovigilance, and prevention research. The transfusion service will advise the clinician on the transfusion reaction evaluation and the role of additional testing depending on the likelihood of TACO versus other possible transfusion reactions such as transfusion-related acute lung injury (TRALI).

Resuming transfusions — TACO is a reaction to the volume of the transfusion rather than to any feature (antibody, antigen, infectious agent, or allergen) inherent to the specific unit of blood.

Thus, although extensive published data are not available to guide decision-making, it makes intuitive sense that if the individual is no longer in a fluid overload state and if they still require the transfusion, it can be resumed. However, from a practical standpoint, it takes time to evaluate the individual, determine the likely cause of respiratory symptoms, and provide supportive care and diuresis. In the majority of cases, the four-hour limit for completing the transfusion will have passed by the time the question arises regarding whether the transfusion can be resumed.

In rare cases in which the pulmonary edema has been adequately treated, further transfusion is indicated, and there is sufficient time to finish the transfusion in under the four-hour limit, the transfusion can be resumed. (See "Practical aspects of red blood cell transfusion in adults: Storage, processing, modifications, and infusion", section on 'Infusion rate'.)

For future transfusions, the transfusion service may provide consultation regarding the option of using smaller units or reducing the volume of the component. (See 'Reducing RBC volume' below.)

PREVENTION

Overview of prevention — There are two major approaches to reducing the risk of TACO:

●Avoiding unnecessary transfusion by using appropriate transfusion thresholds and transfusing the appropriate number of units of blood products. (See "Indications and hemoglobin thresholds for RBC transfusion in adults" and "Platelet transfusion: Indications, ordering, and associated risks", section on 'Indications for platelet transfusion' and "Clinical use of plasma components", section on 'Indications' and "Cryoprecipitate and fibrinogen concentrate", section on 'Differences between them' and "Use of blood products in the critically ill" and "Perioperative blood management: Strategies to minimize transfusions".)

●Transfusing one unit of red blood cells (RBCs) and waiting to assess the patient's response before giving a second unit is prudent and may be especially helpful in high-risk patients; this approach is reasonable for many patients who are not actively bleeding.

●Limiting transfusion of RBCs to two units per day in patients who are not actively bleeding.

●When transfusion is required, avoiding rapid transfusion rates and reducing the volume of the transfusion and/or the patient's intravascular volume. (See 'Transfusion rates' below and 'Diuresis' below.)

●The transfusion service may be able to assist with reducing the volume of the blood components. (See 'Reducing RBC volume' below.)

The use of a pre-transfusion checklist and/or institutional guidelines or order sets may be helpful in ensuring that these issues are addressed [4,25]. However, such institution-wide policies should not take the place of the judgment of the treating clinicians regarding the indications for and administration of blood components for any particular patient.

RBCs are used to replace intraoperative blood loss when a transfusion threshold is met, as discussed separately. (See "Intraoperative transfusion and administration of clotting factors", section on 'Red blood cells'.)

Transfusion rates — The risk of TACO can be reduced by avoiding overly rapid transfusion rates. A transfusion rate of approximately 2.0 to 2.5 mL/kg per hour is reasonable for routine transfusions of blood components, depending upon the clinical situation and the patient's ability to handle the volume load.

For an average sized adult, we use the following infusion rates [26]:

●One unit of packed RBCs with a volume of 350 mL should be transfused at a rate of 1 to 2 mL/minute for the first 15 minutes, followed by transfusion of the remainder typically over 1.5 to 2 hours.

●A pool of four to six units of whole blood derived platelets or one apheresis unit of platelets with a volume of 200 to 300 mL should be transfused at a rate of 2 to 5 mL/minute for the first 15 minutes, followed by transfusion of the remainder typically over one to two hours as tolerated.

●One unit of any plasma product (eg, Fresh Frozen Plasma [FFP]) with a volume of 200 to 250 mL should be transfused at a rate of 2 to 5 mL/minute for the first 15 minutes, followed by transfusion of the remainder over 30 to 60 minutes as tolerated.

Patients deemed to be at risk of TACO (small stature or low body weight, older adults, known or suspected decreased cardiac or kidney function) (see 'Pathophysiology and risk factors' above) can generally be safely transfused at an initial rate of 1 mL/kg per hour, which can be gradually increased. Diuretics can be used if needed. Such patients should also be monitored more closely during the transfusion for signs and symptoms of TACO. (See 'Monitoring' above.)

Diuresis — Diuresis may be appropriate in selected individuals, including those already receiving chronic diuretic therapy, those known to require diuresis with previous transfusions, those at high risk of TACO, those who are in heart failure (HF), and those with a history of TACO. When used, diuretics are typically given before transfusion and, if necessitated by the patient's clinical response, after, or even during, transfusion. Dosage is based on the patient's weight and particular clinical situation, although a common prescription would be furosemide 40 mg or equivalent, given orally or intravenously as necessary.

Reducing RBC volume — The total volume administered with the transfusion may be reduced by one of the following:

●If the time for transfusion of a full unit of blood is expected to exceed four hours based on the patient's prior response to transfusion, the blood bank may be able to provide smaller "split" units.

●The blood bank can centrifuge RBCs or platelets immediately prior to their administration to remove the anticoagulant/preservative solution or plasma, respectively, and reduce the volume.

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: Transfusion and patient blood management".)

SUMMARY AND RECOMMENDATIONS

●Definition, pathophysiology, and risk factors – Transfusion-associated circulatory overload (TACO) is a form of circulatory volume overload that can occur with transfusion of any blood component. It is defined as new onset dyspnea within 12 hours of transfusion, with specific criteria listed above. Risk factors include pre-existing cardiac and possibly kidney dysfunction, extremes of age, small stature, low body weight, greater number of units transfused, and faster rate of infusion. (See 'Definition' above and 'Pathophysiology and risk factors' above.)

●Incidence – The true frequency of TACO is difficult to assess; under-reporting is likely. TACO is estimated to occur in 1 percent or more of transfused individuals overall, and at greater frequency in individuals in the intensive care unit (ICU). TACO is more common than anaphylaxis, acute hemolytic transfusion reactions (AHTR), or transfusion-related acute lung injury (TRALI). TACO is the most common cause of death from a transfusion. (See 'Epidemiology' above.)

●Clinical features – The possibility of TACO should be considered in any patient who has respiratory distress (dyspnea, orthopnea) or hypertension during or within 12 hours after the end of a transfusion, especially in individuals with underlying heart disease, in the setting of positive fluid balance, and in the ICU. (See 'Clinical presentation' above.)

●Evaluation – Individuals receiving a transfusion are monitored periodically and instructed to report any concerning symptoms including respiratory distress; additional monitoring may be appropriate in those at higher risk of TACO. If a patient develops respiratory distress, the examination focuses on cardiovascular and pulmonary findings and assessment for other possible causes of dyspnea. Oxygenation status should be assessed, and chest imaging is usually indicated. TACO can cause hypoxia, jugular venous distention, pulmonary rales, an S3 gallop, pulmonary edema on chest imaging, and elevated BNP or NT-BNP. (See 'Diagnostic testing' above.)

●TACO versus TRALI and other causes of dyspnea – The differential diagnosis includes other transfusion reactions, especially TRALI (table 1); other causes of heart failure; and pulmonary embolism. (See 'Differential diagnosis' above.)

●Management – Treatment of TACO is similar to that of other causes of cardiogenic pulmonary edema and includes fluid mobilization, supplementary oxygen, and assisted ventilation if indicated. All cases of suspected TACO should be reported to the transfusion service and/or blood bank. (See 'Management' above.)

●Prevention – Strategies to reduce the risk of TACO include avoiding unnecessary transfusions; transfusing only the number of units needed; avoiding overly rapid transfusion rates and in some cases administering a diuretic or reducing the volume of the transfused product. The transfusion medicine service can help to reduce the volume of the product. (See 'Prevention' above.)

●Other transfusion reactions

•General approach – (See "Approach to the patient with a suspected acute transfusion reaction".)

•Transfusion-related acute lung injury (TRALI) – (See "Transfusion-related acute lung injury (TRALI)".)

•Hemolytic reactions – (See "Hemolytic transfusion reactions".)

•Febrile nonhemolytic reactions (FNHTR) – (See "Immunologic transfusion reactions", section on 'Febrile nonhemolytic transfusion reactions'.)

•Immunologic/allergic reactions – (See "Immunologic transfusion reactions".)

•Sepsis – (See "Transfusion-transmitted bacterial infection".)

•Air embolism – (See "Air embolism".)

•Transfusion-associated graft-versus-host disease (ta-GVHD) – (See "Transfusion-associated graft-versus-host disease".)

•Transfusional iron overload – (See "Approach to the patient with suspected iron overload", section on 'Transfusional iron overload'.)

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