SAN DIEGO – , according to research presented at the annual meeting of the American Association of Blood Banks.
Compared with other RBC products, those derived from apheresis significantly increased pulmonary cell interleukin (IL)–6 and IL-8 production, and this was further exacerbated by cell stretching. Conversely, red cell–filtered products appeared to be the least likely to cause cell injury.
“Several studies have shown that red blood cell transfusion is associated with acute lung injury, and transfusion induces leakage in ICU patients,” said lead study author Mathijs Wirtz, MD, of the Academic Medical Center, Amsterdam.
ICU patients who did not receive any transfusions had significantly lower leakage than those who were transfused. “There also seems to be a synergy between transfusion and mechanical ventilation,” Dr. Wirtz said.
Studies have also shown that there are differences in the prevalence of transfusion-related acute lung injury, when comparing Europe to the United States. Storage and manufacturing methods do differ between Europe and the United States, Dr. Wirtz noted. “This led to our hypothesis that lung injury inflicted by red blood cell transfusion is influenced by manufacturing methods.”
In this study, Dr. Wirtz and his colleagues investigated the response of pulmonary cells to the different methods of manufacturing RBC products. Using type A or B blood obtained from eight donors, a variety of RBC products were manufactured for the study, including whole-blood filtered, red-cell filtered, apheresis derived, and whole-blood derived.
For measuring thrombin generation and analyzing extracellular vesicles (EV), supernatants were prepared after 4-5 days of storage for fresh and 41-42 days for stored. The researchers selected A549 type II alveolar cells to seed onto flexible membranes, which were then incubated with RBC supernatant also stretched 25% using a cell stretcher.
After 24 hours, the production of IL-8 and IL-6 was measured.
Both fresh and stored supernatants that were derived from apheresis significantly increased the production of IL-6 and IL-8 in pulmonary cells, compared with nonincubated controls and most of the other RBC products. The production of IL-6 and IL-8 was exacerbated by cell stretching.
Average IL-6 production in nonstretched cells was 91 pg/mL for fresh and 87 pg/mL for expired (P less than .05 vs. control and other RBC products). For stretched cells, it was 130 pg/mL and 150 pg/mL (P less than .05 vs. control). For controls, mean nonstretched and stretched production was 21 pg/mL and 85 pg/mL.
Mean IL-8 production in nonstretched cells was 2,100 pg/mL for fresh and 1,900 pg/mL for stored (P less than .05 vs. control and other RBC products). For stretched cells, the means were 4,100 pg/mL for fresh and 5,200 pg/mL for stored (P less than .05 vs. control).
The average nonstretched and stretched control IL-8 production was 1,200 pg/mL for fresh and 4,300 pg/mL for stored.
Products derived from apheresis also demonstrated a significantly higher ability to generate thrombin, compared with other RBC products, and a significantly increased number of RBC-derived EVs, compared with filtered red cell and whole blood–derived products (P less than .05).
However, incubated stretched cells from stored whole blood–filtered products had higher IL-8 production (16,000 pg/mL), compared with other products and stretched controls. The lowest mean levels of IL-6 were observed in supernatants derived from red cell–filtered products (nonstretched fresh and expired, 12 pg/mL and 8 pg/mL; stretched, 40 pg/mL and 36 pg/mL) and they did not appear to activate pulmonary cells. Levels of EVs were also low, compared with other blood products.
“We can conclude that manufacturing methods contribute to the differences in inducing lung injury, and especially the apheresis-derived products, which induced the most consistent injury in our model,” Dr. Wirtz said. “The red cell–filtered products appeared to be the safest.”
Dr. Wirtz had no disclosures.