Coagulopathy frequently complicates venovenous extracorporeal membrane oxygenation (VV ECMO) procedures, yet its underlying mechanism remains elusive. This retrospective study aimed to identify factors contributing to coagulopathy during VV ECMO by analyzing clinical data and employing proteomic approaches. A prospective cohort was also examined for validation.

We retrospectively analyzed clinical data from 51 patients undergoing VV ECMO between January 2015 and April 2021, categorizing them into coagulopathy(n = 21), defined by elevated levels of D-dimer and decreased fibrinogen in plasma that were reversible by circuit exchange, and non-coagulopathy(n = 30) groups. Plasma samples collected on days 0–2(D1), days 3–5(D4), and days 6–8(D7) were subjected to proteomics and Luminex assay. Additionally, oxygenator fiber samples were collected from a prospective cohort between May 2022 and August 2022 for scanning electron microscopy.

Inflammation emerged as a pivotal factor in coagulopathy development during VV ECMO, as evidenced by elevated interleukin-6 levels on D1 and increased leukocyte and neutrophil counts on D4. Proteomics analysis identified a significant elevation of S100A8 and S100A9 in the plasma of coagulopathy patients throughout VV ECMO, findings confirmed by Luminex assay. In the prospective cohort, thrombosis and leukocyte accumulation were observed on oxygenator fibers from coagulopathy patients, along with elevated levels of S100A8 and S100A9 in plasma.

Coagulopathy during VV ECMO is associated with heightened levels of proinflammatory proteins S100A8 and S100A9 in plasma, accompanied by leukocyte accumulation on oxygenator fibers. These findings emphasize the potential therapeutic target against coagulopathy during VV ECMO.