Biomarkers and Diagnostic Criteria for Early Differentiation of Transfusion- Related Acute Lung Injury and Transfusion-Associated Circulatory Overload: A Systematic Review

Author(s): Rana Ahmed, Salis Aizaz Rasool, Dhruba Dhar, Istia Mumtahina Meem, Shashwat Shetty, Ahmad Abdurrahman Thaika, Shahmeen Rasul, Manahil Awan, Shahzad Ahmad

Transfusion-related respiratory complications, including transfusionrelated acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO), are major causes of morbidity and mortality in transfused patients. Differentiating these conditions is challenging due to overlapping clinical presentations but is critical for appropriate management. This systematic review synthesizes current evidence on biomarkers and diagnostic criteria to enable early and accurate differentiation of TRALI and TACO. A comprehensive literature search identified six studies examining cardiac biomarkers (BNP, NT-proBNP), endothelial injury markers (syndecan-1), and inflammatory cytokines (IL-6, IL-8, TNF-α). NTproBNP and syndecan-1 were consistently elevated in TACO, reflecting circulatory overload and glycocalyx disruption, whereas inflammatory cytokines were associated with TRALI, indicating immune-mediated capillary leak. Integrated approaches combining biomarkers with clinical assessment and imaging improved diagnostic accuracy, particularly in overlapping cases. Limitations include small sample sizes, single-center designs, and variability in biomarker thresholds. These findings support the use of a multimarker strategy to guide early differentiation, optimize targeted interventions, and reduce misclassification. Future research should focus on prospective validation of biomarker algorithms and their impact on patient outcomes.