Effect of red blood cell transfusion on inflammation, endothelial cell activation and coagulation in the critically ill

Abstract

Background and Objectives: Red blood cell (RBC) transfusion is a frequently applied intervention in an intensive care unit. However, transfusion is associated with adverse outcomes including organ failure and thrombo-embolic events. Mechanisms of these effects are not known but may be related to activation of the endothelium or of the coagulation or inflammatory system. We hypothesized that a RBC transfusion in the critically ill would result in further activation of these systems. Materials and Methods:In 74 non-bleeding critically ill patients receiving one RBC unit, markers of inflammation, endothelial cell activation and coagulation were measured before transfusion, at 1 h after transfusion and 24 h after transfusion. The impact of disease severity of the recipient on these changes was assessed by comparing septic and non-septic patients (according to sepsis-3 definition) and by correlation of biomarkers with the sequential organ failure assessment (SOFA) score.Results: Levels of von Willebrand Factor (vWF), soluble ICAM-1, soluble thrombomodulin, fibrinogen and d-dimer were already high at baseline, whereas ADAMTS13 levels were low. VWF levels increased significantly 24 h after RBC transfusion (median 478% (338-597) vs. 526% (395-623), p = 0.009). The other biomarkers did not change significantly. Post transfusion change was not dependent on the presence of sepsis and was not correlated with SOFA score. Conclusion:RBC transfusion in critically ill patients was associated with an increase in circulating vWF levels, suggesting a further increase in activation of the endothelium, a finding that was independent of the presence of sepsis or organ injury level.

Exploring NT‐proBNP, syndecan‐1, and cytokines as biomarkers for transfusion‐associated circulatory overload in a critically ill patient population receiving a single‐unit red blood cell transfusion

“…Samples were collected in ethylenediaminetetraacetic acid (EDTA) tubes and centrifuged at 1500 g for 20 min, the plasma was then stored at −80°C until further analysis. Soluble syndecan‐1, IL‐6, and other biomarkers were analyzed within the prospective cohort using a custom designed human pre‐mixed multi‐analyte luminex assay as described by the manufacturer (Luminex R&D Systems Inc., Minneapolis, MN, USA) after data collection was finished 20 . NT‐proBNP, IL‐10, and IL‐8 were measured in EDTA plasma 4 years after completion of data collection using ELISA (R&D Systems Inc., Minneapolis, MN, USA).…”

“…There were 64 patients with all 3 blood samples present included in this study out of 74 patients that participated in the prospective study. 20 Three patients were excluded because of missing clinical data. Seven patients were excluded because of missing samples.…”

Clinical Effects and Possible Mechanisms of Transfusion-Related Immunomodulation

“…Another study found an increase in levels of von-Willebrand-factor antigen in critically ill patients receiving a RBC transfusion. The von Willebrand factor antigen has a causal role in the activation of endothelium and also in the development of thrombi formation [79]. After cardiovascular surgery, the levels of plasma tissue factor are persistent high for 30 days, which can increase the risk of VTE [80].…”

Red cell extracellular vesicles and coagulation activation pathways

“…Despite the large number of studies, their observational design hampers a conclusion of causality between PRBC transfusion and VTE. Mechanistically, most clinical situations requiring RBC transfusion are likely to have some level of coagulation activation and/or inflammation which might be enhanced following transfusion [71 ▪ ]. Both stored RBCs and sREVs can provide a procoagulant surface to enhance thrombin formation, although this activity may be proportionally higher with sREVs than RBCs in individual units [31].…”