Plasma Transfusion Products and Contamination with Cellular and Associated Pro-Inflammatory Debris

Abstract

Stored plasma products are widely regarded as being functionally acellular, obviating the need for leukoreduction. We tested the hypothesis that donor plasma is contaminated by leukocytes and platelets, which, after frozen storage, would release cellular debris in quantities sufficient to elicit significant pro-inflammatory responses. Samples of never-frozen liquid plasma from 2 regional Level I trauma centers were analyzed for leukocyte and platelet contamination. To determine if the cellular contamination and associated debris found in liquid plasma were at levels sufficient to evoke an innate immune response, known quantities of leukocytes were subjected to a freeze-thaw cycle, added to whole blood, and the magnitude of the inflammatory response was determined by induction of interleukin-6. Units of never-frozen plasma from 2 regional Level I trauma centers located in Alabama and Louisiana contained significant amounts of leukocyte contamination (Louisiana, n= 22; 17.3 ± 4.5 million vs Alabama, n= 22; 11.3 ± 2.2 million) and platelet contamination (Louisiana, n= 21; 0.86 ± 0.20 billion vs Alabama, n= 22; 1.0 ± 0.3 billion). Cellular debris from as few as 1 million leukocytes induced significant increases in interleukin-6 levels (R2= 0.74; p < 0.0001). Stored plasma units from trauma center blood banks were highly contaminated with leukocytes and platelets, at levels more than 15-fold higher than sufficient to elicit exvivo inflammatory responses. In light of paradigm shifts toward the use of more empiric plasma for treatment of hypovolemia, this study suggests that new manufacturing and quality-control processes are needed to eliminate previously unrecognized cellular contamination present in stored plasma products.