Inflammatory pathways in transfusion-associated circulatory overload

Abstract

Transfusion-associated circulatory overload (TACO) is a leading cause of transfusion-associated mortality. TACO is thought to result from hydrostatic forces in the vascular space, leading to transudative pulmonary edema. Recent studies suggest that TACO is not solely a volume overload phenomenon, but may involve inflammatory processes. This study aimed to further explore the presence of inflammation in patients with TACO. We conducted a retrospective study with 3 cohorts receiving red blood cell transfusion: (1) patients having TACO as defined by a national hemovigilance case surveillance classification (conventional TACO [cTACO], n = 33); (2) patients having symptoms consistent with TACO but not completely meeting reporting criteria (institutional TACO [iTACO], n = 33); and (3) a patient cohort who experienced uncomplicated transfusions (n = 6). Samples from before transfusion, after transfusion, and 8 to 36 hours after transfusion were examined. Samples were analyzed for levels of tumor necrosis factor α, interleukin-1α (IL-1α), IL-6, IL-8, IL-10, C-reactive protein, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1, atrial natriuretic peptide, cardiac troponin, and N-terminal pro-B-type natriuretic peptide. Patients with cTACO and iTACO had an elevated body temperature, higher heart rate, and lower oxygen saturation after transfusion, whereas only patients with cTACO had higher blood pressures. Levels of key proinflammatory cytokines, IL-6, and IL-8 were elevated in patients with cTACO and iTACO after transfusion, whereas ICAM-1 was elevated only in patients with iTACO after transfusion. Our results suggest that inflammatory pathways may be invoked in patients with TACO. Patients with iTACO showed a more distinctive inflammatory profile, suggesting a gray area between transfusion-related acute lung injury and TACO.

Inflammatory Response in TACO

Figure 1.

Heat map of biomarkers. Different colors depict z scores above or below the mean. The concentrations increase as the color changes from blue to orange. CRP, C-reactive protein; TNF-α, tumor necrosis factor α.