Inflammatory Pathways in Transfusion-Associated Circulatory Overload Open Access

• Elevations in levels of inflammatory cytokines are present in patients with transfusion-associated circulatory overload (TACO)

• A subset of such patients exhibiting nonclassical signs of volume overload may exhibit greater elevations of pro-inflammatory cytokines.

Transfusion-associated circulatory overload (TACO) is a potentially fatal pulmonary transfusion complication and a leading cause for transfusion associated mortality. TACO is thought to be the result of hydrostatic forces in the vascular space, leading to transudative pulmonary edema. Recent studies have suggested that TACO is not solely a volume overload phenomenon, but that inflammatory processes may have a role. The aim of this study was to further explore the presence of inflammation in TACO patients. We conducted a retrospective study with three cohorts receiving red blood cell transfusion. 1; patients having TACO as defined by a national hemovigilance case surveillance classification (cTACO, n = 33), 2; patients having symptoms consistent with TACO, but not completely meeting reporting criteria (institutional TACO, iTACO, n = 33), 3; a patient cohort experiencing uncomplicated transfusions (UCT, n = 6). Samples from before transfusion, after transfusion and 8-36 hours after transfusion were examined. Samples were analysed for levels of TNF-α, IL-1α, IL-6, IL-8, IL-10, CRP, ICAM-1, VCAM-1, ANP, cardiac troponin, and NT-proBNP. cTACO and iTACO patients had an elevated body temperature, higher heart rate and lower oxygen saturation after transfusion, whereas only cTACO patients manifested higher blood pressures. Levels of key proinflammatory cytokines, IL-6 and IL-8 levels were elevated in both cTACO and iTACO patients after transfusion, while ICAM-1 was elevated only in iTACO patients after transfusion. Our results suggest that inflammatory pathways may be invoked in patients with TACO. Moreover, iTACO patients showed a more distinctive inflammatory profile, suggesting a grey area between transfusion-related acute lung injury and TACO.