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

BACKGROUND: Transfusion‐associated circulatory overload (TACO) is the leading cause of transfusion‐related 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 transfusion‐related 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 for TACO 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.