Transfusion-associated circulatory overload
Transfusion-associated circulatory overload (TACO) is a serious complication of blood transfusion characterized by acute pulmonary edema resulting from excessive intravascular volume, typically manifesting as hydrostatic cardiogenic edema within 6 hours of transfusion.[1] It arises when the transfused blood volume overwhelms the patient's cardiovascular capacity, leading to fluid leakage into the lungs and impaired gas exchange.[2] TACO is the leading cause of transfusion-related fatalities in many hemovigilance reports, accounting for 39.4% of such deaths from 2010 to 2023 (SHOT report) and 34% from 2018 to 2022 (FDA data).[3][4] Incidence varies but is estimated at 1% to 8% of transfusions under active surveillance, with higher rates (up to 11%) in critically ill or elderly postoperative patients; a 2025 meta-analysis reports 22.2 cases per 1000 patients overall.[5][6] Risk factors include advanced age (over 60 years), preexisting cardiovascular or renal disease, chronic obstructive pulmonary disease (COPD), female sex, and rapid or large-volume transfusions.[2] The pathophysiology involves a "two-hit" model: an initial patient vulnerability (e.g., reduced cardiac reserve) combined with transfusion-related factors like infusion speed or plasma volume in blood products.[5] Symptoms typically develop during or shortly after transfusion and include acute dyspnea, orthopnea, cough, tachycardia, hypertension, and signs of fluid overload such as peripheral edema or elevated jugular venous pressure.[1] In severe cases, patients may experience cyanosis, severe headache, dizziness, or require mechanical ventilation, with mortality rates reaching 21%.[2] Diagnosis relies on clinical criteria, such as the 2016 National Healthcare Safety Network (NHSN) definition requiring at least three of: acute respiratory distress, positive fluid balance, elevated brain natriuretic peptide (BNP), radiographic pulmonary edema, signs of left heart failure (such as elevated central venous pressure), or evidence of fluid overload. Note that the current NHSN protocol (as of 2025) extends the time frame to within 12 hours of transfusion cessation.[5][7] Supporting tests include chest X-rays showing bilateral opacities, echocardiography to assess cardiac function, and BNP levels to differentiate from transfusion-related acute lung injury (TRALI).[1] Management focuses on immediate supportive care: halting the transfusion, administering supplemental oxygen, and using diuretics like furosemide to reduce volume overload.[8] More severe cases may necessitate noninvasive ventilation (e.g., CPAP) or intensive care unit admission.[2] Prevention strategies emphasize patient risk assessment prior to transfusion, employing restrictive transfusion thresholds, slowing infusion rates (e.g., 1-2 mL/kg/hour for red blood cells), and considering prophylactic diuretics in high-risk individuals.[1] Ongoing hemovigilance and clinician education are crucial to mitigate this preventable complication.[8]Introduction
Definition
Transfusion-associated circulatory overload (TACO) is defined as new or worsening respiratory distress due to circulatory overload from transfusion of blood products, manifesting as acute pulmonary edema within 12 hours of the start of transfusion.[9] It is classified as a non-hemolytic transfusion reaction, arising from volume overload rather than immune-mediated mechanisms.[10] The key physiological hallmark of TACO is hydrostatic pulmonary edema resulting from an increase in intravascular volume that exceeds the recipient's cardiac compensatory capacity, leading to elevated hydrostatic pressure in the pulmonary capillaries.[9] This distinguishes TACO from chronic fluid overload conditions, as symptoms specifically emerge during or shortly after transfusion, emphasizing the temporal link to the procedure.[10] The 2019 revised criteria from the International Society of Blood Transfusion (ISBT), International Haemovigilance Network (IHN), and AABB, based on the 2018 surveillance case definition, require new or worsening respiratory symptoms within 12 hours of transfusion, evidence of hydrostatic pulmonary edema (such as elevated BNP levels, radiographic findings, or response to diuretics), and exclusion of transfusion-related acute lung injury (TRALI) or other alternative causes for diagnosis.[9] TACO is often confused with TRALI due to overlapping respiratory symptoms, but the former is characterized by cardiogenic rather than non-cardiogenic edema.[10]Epidemiology
Transfusion-associated circulatory overload (TACO) has an incidence that varies widely, ranging from 1% to 12% of blood transfusions depending on the patient population and surveillance methods.[11] In hemovigilance reports, rates are typically lower at around 1%, while active surveillance in high-risk groups such as postoperative elderly patients shows rates up to 8%.[5] Critically ill patients in intensive care units experience an incidence of approximately 1%.[12] TACO is a leading cause of transfusion-related morbidity and mortality in multiple regions, including the United States, Europe, Canada, and the United Kingdom, where it accounts for 30% to 44% of reported transfusion-associated fatalities in recent federal and hemovigilance data from 2010 to 2022.[4][5] In the United States, it represented 34% of transfusion-related deaths reported to the Food and Drug Administration between fiscal years 2018 and 2022.[4] Underreporting remains a significant challenge, as TACO is frequently misdiagnosed as heart failure exacerbation or other cardiopulmonary events, leading to hemovigilance systems capturing only 0.01% to 1% of cases compared to higher rates in prospective studies.[13][14] Active surveillance efforts reveal that official reporting underestimates the true burden by a factor of 10 or more in some settings.[8] Demographic trends indicate a higher incidence in patients over 70 years, who comprise the majority of cases and face rates up to 8% in hospitalized or postoperative settings, particularly those with comorbidities such as cardiac or renal disease.[5][15] Global variations exist, with higher reported rates in the United States compared to Europe, potentially attributable to differences in transfusion volumes, patient selection, and surveillance practices.[16] The 2019 revision of international TACO surveillance criteria by the International Society of Blood Transfusion has contributed to increased reporting, with hemovigilance data from 2020 to 2024 showing record-high case numbers in the United Kingdom and stable underlying incidence amid rising awareness.[9][17][18] The case fatality rate for TACO ranges from 5% to 15%, with mortality often exacerbated by underlying conditions rather than the transfusion event itself.[19][20]Clinical Presentation
Symptoms and Signs
Transfusion-associated circulatory overload (TACO) manifests primarily through acute respiratory distress, often developing during or within 6 hours of transfusion completion.[5] Respiratory symptoms include acute dyspnea, orthopnea, tachypnea (respiratory rate >20 breaths per minute), and hypoxemia (SpO2 <90% on room air).[5][21] These features arise from hydrostatic pulmonary edema due to volume overload.[16] Cardiovascular signs are prominent and help distinguish TACO from other transfusion reactions, such as transfusion-related acute lung injury (TRALI), where hypotension is more common.[5] Patients typically exhibit tachycardia (heart rate >100 beats per minute), hypertension (systolic blood pressure often >20 mmHg above baseline or >160 mmHg), elevated jugular venous pressure.[5][21] Pulmonary examination reveals bilateral crackles or rales on auscultation, indicative of pulmonary edema.[5] Radiographic findings may include bilateral infiltrates, such as Kerley B lines, supporting the diagnosis of hydrostatic edema.[22] Other associated signs encompass a non-productive cough, with symptoms developing within 1-6 hours post-transfusion. Symptoms often resolve with treatment within days.[21] In pediatric patients, particularly young children or infants, additional signs of respiratory distress such as grunting and nasal flaring may occur, often underemphasized in adults.[23] These manifestations highlight the vulnerability of younger children to rapid fluid shifts during transfusion.[23]Risk Factors
Patient-related risk factors for transfusion-associated circulatory overload (TACO) include extremes of age, such as children under 2 years and adults over 65 years, which predispose individuals to impaired cardiac reserve and fluid handling.[24] Preexisting heart failure significantly increases susceptibility due to reduced ventricular compliance and inability to accommodate additional volume.[5] Chronic kidney disease further elevates risk by compromising fluid excretion and exacerbating volume overload.[25] Pulmonary hypertension also contributes as a non-modifiable factor by increasing right ventricular strain and pulmonary vascular resistance.[26] Procedural characteristics heighten TACO risk through direct contributions to acute volume expansion. Transfusion rates exceeding 100-150 mL per hour promote rapid hydrostatic pressure changes, while large-volume transfusions greater than 1 L in 24 hours overwhelm compensatory mechanisms.[19] A positive fluid balance exceeding 500 mL prior to transfusion similarly amplifies overload by establishing a baseline of excess intravascular volume.[27] Comorbidities such as hypoalbuminemia (serum albumin below 3 g/dL) impair oncotic pressure and promote fluid extravasation into tissues, while a history of prior TACO episodes indicates recurrent vulnerability often linked to unresolved underlying issues.[28] Anemia necessitating urgent transfusion, particularly in emergency settings, compounds risk by combining hypovolemia correction with rapid volume administration.[27] Among these, non-modifiable factors like cardiac dysfunction predominate, accounting for the majority of cases in clinical studies, with odds ratios for heart failure ranging from 2.0 to 6.6.[27][29] Modifiable procedural elements, such as transfusion volume and rate, offer opportunities for mitigation. Recent studies from 2021-2024 emphasize emerging risks including obesity (BMI greater than 30) and emergency transfusions, which are associated with higher fluid shifts and cardiorenal strain in vulnerable populations like oncology patients.[30][31] Recent hemovigilance data (as of 2024) indicate rising TACO morbidity and mortality, emphasizing ongoing risks in vulnerable populations.[18]Diagnosis
Diagnostic Criteria
The diagnosis of transfusion-associated circulatory overload (TACO) relies on the revised international surveillance case definition developed by the International Society of Blood Transfusion (ISBT) Working Party on Granulocyte Immunology in 2018 and published in 2019, which updated earlier criteria by extending the temporal window and incorporating supportive biomarkers for improved specificity.[10] This revision addressed limitations in the prior 2011 ISBT definition, such as its stricter 6-hour onset requirement and lack of biomarker integration, enhancing capture of cases while distinguishing TACO from transfusion-related acute lung injury (TRALI).[32] Under the 2018 ISBT criteria, TACO requires at least three of the following five criteria occurring during or up to 12 hours after transfusion cessation: (A) acute or worsening respiratory compromise (such as tachypnea, dyspnea, cyanosis, or decreased oxygen saturation); (B) evidence of pulmonary edema (identified via clinical signs like crackles or orthopnea, or imaging findings like bilateral infiltrates, pleural effusions, or Kerley B lines on chest X-ray); (C) cardiovascular changes, including tachycardia, left atrial hypertension (assessed by echocardiography showing elevated left atrial pressure), widened pulse pressure, or hypertension not attributable to the patient's baseline condition; (D) evidence of fluid overload, such as a positive fluid balance, acute weight gain, or rapid response to diuretic therapy with resolution of symptoms; (E) elevated or rising levels of B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), where a post-transfusion NT-proBNP level exceeding 1.5 times the pre-transfusion value (or above age-adjusted norms, typically >300 pg/mL in non-elderly adults) supports the diagnosis, while a normal post-transfusion level argues against it.[10][33] Diagnosis excludes cases with demonstrable TRALI risk factors, such as donor-specific anti-human leukocyte antigen or anti-human neutrophil antigen antibodies, and mandates ruling out concurrent infection, anaphylaxis, or other non-transfusion-related causes through clinical evaluation and laboratory tests.[10] Supporting diagnostic tests emphasize objective confirmation of volume overload. Chest X-ray is recommended to demonstrate bilateral pulmonary infiltrates or edema consistent with hydrostatic rather than permeability mechanisms.[10] Echocardiography aids by quantifying left atrial pressure elevation or systolic/diastolic dysfunction indicative of cardiogenic overload.[10] Serial BNP or NT-proBNP measurements, with a post-transfusion rise greater than 50% from baseline, provide high sensitivity (up to 90%) for TACO in validation studies, particularly when pre-transfusion levels are available for comparison.[33] The 2018 criteria were validated to capture 76% of cases endorsed by participating hemovigilance systems.[32] A systematic review indicates NT-proBNP thresholds demonstrate moderate diagnostic performance (AUC 0.70) in distinguishing TACO from mimics like TRALI.[33] In March 2021, the National Healthcare Safety Network (NHSN) updated its protocol to align with the 2018 ISBT definition for TACO surveillance.[7]Differential Diagnosis
Transfusion-associated circulatory overload (TACO) must be differentiated from other causes of acute respiratory distress occurring during or shortly after blood transfusion, as overlapping symptoms such as dyspnea and hypoxemia can lead to misdiagnosis. The primary transfusion-related differential is transfusion-related acute lung injury (TRALI), while non-transfusion conditions including exacerbations of underlying heart failure, iatrogenic fluid overload from intravenous fluids, pneumonia, aspiration pneumonitis, and anaphylactic reactions also warrant consideration.[5][34] TRALI presents as non-cardiogenic pulmonary edema mediated by donor antibodies or biological response modifiers, typically featuring hypotension, fever, and transient leukopenia within 6 hours of transfusion, in contrast to TACO's cardiogenic hydrostatic edema associated with hypertension (often >160 mm Hg systolic) and evidence of positive fluid balance.[5][35] B-type natriuretic peptide (BNP) levels are markedly elevated in TACO (post-transfusion >100 pg/mL or ratio to pre-transfusion ≥1.5), reflecting cardiac strain and volume overload, with a sensitivity of 81%, specificity of 89%, and overall accuracy of 87% for distinguishing it from TRALI, where BNP remains normal or only mildly increased.[36] Chest imaging further aids differentiation: TACO shows a hydrostatic pattern with central edema, pleural effusions, and cardiomegaly, whereas TRALI exhibits a permeability pattern with peripheral infiltrates and normal cardiac silhouette. Response to diuretics is typically rapid in TACO due to volume reduction but absent in TRALI.[5][35]| Feature | TACO | TRALI |
|---|---|---|
| Edema Type | Cardiogenic (hydrostatic) | Non-cardiogenic (permeability) |
| Blood Pressure | Hypertension (>160 mm Hg systolic) | Hypotension |
| BNP Elevation | Significant (>1.5x baseline) | Normal or minimal |
| Fever | Absent or mild | Common |
| Fluid Balance | Positive (overload) | Neutral |
| Diuretic Response | Positive (improved oxygenation) | None |
| Imaging Pattern | Central, with effusions/cardiomegaly | Peripheral, normal heart size |