Transfusion‐associated circulatory overload—a systematic review of diagnostic biomarkers

Abstract

BACKGROUND: Transfusion-associated circulatory overload (TACO) is the leading cause of transfusionrelated major morbidity and mortality. Diagnosing TACO is difficult because there are no pathognomonic signs and symptoms. TACO biomarkers may aid in diagnosis, decrease time to treatment, and differentiate from other causes of posttransfusion dyspnea such a transfusionrelated acute lung injury. STUDY DESIGN AND METHODS:A systematic review of literature was performed in EMBASE, PubMed, the TRIP Database, and the Cochrane Library, from inception to June 2018. All articles discussing diagnostic markers for TACO were included. Non-English articles or conference abstracts were excluded. RESULTS: Twenty articles discussing biomarkers forTACO were included. The majority investigated B-type natriuretic peptide (BNP) and the N-terminal prohormone cleavage fragment of BNP (NT-proBNP), markers of hydrostatic pressure that can be determined within 1 hour. The data indicate that a post/pretransfusion NT-proBNP ratio > 1.5 can aid in the diagnosis of TACO. Posttransfusion levels of BNP less than 300 or NT-proBNP less than 2000 pg/mL, drawn within 24 hours of the reaction, make TACO unlikely. Cut-off levels that exclude TACO are currently unclear. In critically ill patients, the specificity of natriuretic peptides for circulatory overload is poor. Other biomarkers, such as cytokine profiles, cannot discriminate between TACO and transfusion-related acute lung injury. CONCLUSION:Currently, BNP and NT-proBNP are the primary diagnostic biomarkers researched for TACO. An NT-proBNP ratio greater than 1.5 is supportive of TACO, and low levels of BNP or NT-proBNP can exclude TACO. However, they are unreliable in critically ill patients. Other biomarkers, including cytokines and pulmonary edema fluid-to-serum protein ratio have not yet been sufficiently investigated for clinical use. T ransfusion-associated circulatory overload (TACO) is characterized by acute respiratory distress and pulmonary edema with signs of volume overload following transfusion. 1 It is the foremost cause of transfusion-related mortality in Europe, 2-4 Canada 5 and the United States. 6 TACO is currently underrecognized, 7,8 as it is challenging to diagnose due to lack of pathognomonic signs ABBREVIATIONS: AHF = acute heart failure; ARDS = acute respiratory distress syndrome; BALF = bronchoalveolar lavage fluid; BNP = B-type natriuretic peptide; ICU = intensive care unit; IL = interleukin; NPs = natriuretic peptides; NT-proBNP = N-terminal prohormone of BNP; TACO = transfusion-associated circulatory overload; TNCs = transfused negative controls; TRALI = transfusion-related acute lung injury. From the

A consensus redefinition of transfusion‐related acute lung injury

“…In some cases, biomarkers (brain natriuretic peptide [BNP] or NT‐proBNP) at onset of pulmonary symptoms may be useful: when low (BNP < 300 pg/mL or NT‐proBNP < 2000 pg/mL), they can rule out TACO or when high (NT‐proBNP posttransfusion/pretransfusion ratio > 1.5), they may suggest TACO . However, since in critically ill patients and severe TRALI cases these biomarkers are always elevated due to hypoxic vasoconstriction, NT‐proBNP is only likely to be useful in the general patient population and in cases with mild pulmonary symptoms …”

Pulmonary complications of transfusion: Changes, challenges, and future directions

“…and in renal failure due to impaired renal clearance and hypoxic vasoconstriction. 31,32 After excluding ARDS unrelated to transfusion, the absence of significant LAH is pivotal in distinguishing TRALI from TACO ( Table 3).…”

“…Additionally, cytokine levels were not found to be informative in differentiating TACO and TRALI. 32 Although prophylactic loop diuretics are recommended for TACO risk reduction in patients who have risk factors identified by the TACO risk assessment, diuretics may not be appropriate as a universal risk-reduction measure. These drugs are associated with adverse events, especially in the elderly, 35,36 and therefore their use in transfusion must be judicious.…”

NT‐proBNP levels in the identification and classification of pulmonary transfusion reactions

“…Multiple studies have examined the role of biomarkers in the identification or differentiation of pulmonary transfusion reactions. 5,8,9 Natriuretic peptides have been studied most frequently and are hormones released by cardiac myocytes in the setting of increased blood volume or ventricular wall stress. Brain natriuretic peptide (BNP) or N-terminal prohormone brain natriuretic peptide (NT-proBNP) have been shown to be elevated in cases of TACO and ARDS with transfusion and less commonly with TRALI.…”