ABSTRACT NUMBER: ESOC2026A972 NEUTROPHIL EXTRACELLULAR TRAPS IN PATIENTS WITH INTRACEREBRAL HEMORRHAGE

Abstract Background and aims Secondary mechanisms after spontaneous intracerebral hemorrhage (ICH) include neuroinflammation and development of perihematomal edema. Neutrophil extracellular traps (NETs) are involved in disease processes affecting the nervous system, including immunothrombosis and blood-brain barrier disruption. We aimed to assess NETs in ICH and their potential contribution to outcome measures. Methods We conducted a prospective, single-center cohort study recruiting ICH patients and collected clinical, laboratory, imaging, and 3-month outcome data. NET components (citrullinated histone H3[H3Cit]-DNA-complexes, myeloperoxidase (MPO)-DNA-complexes, cell-free DNA [cfDNA]), and DNase activity were measured in plasma collected on admission, on day 2/3, and on day 6 (±1 day) after admission. We assessed ICH volume and perihematomal edema (PHE) semiquantitatively. Results We enrolled 50 ICH patients with a median ICH volume of 16 ml(IQR 5.8-38), and a median PHE volume of 11 ml(IQR 5-26). Compared to healthy controls, NETs were detectable in ICH patients on admission at higher levels (H3Ccit-DNA, p<0.001; cfDNA, p<0.001) together with lower DNase activity (p=0.012). During the first 6 days after ICH we observed an increase of NET components H3Cit-DNA (baseline, median 6.0 ng/ml vs. day 6, 12.0 ng/ml; p<0.001), MPO-DNA (1.4 ng/ml vs. 2.6 ng/ml, p<0.001) and cfDNA (115 ng/ml vs. 137 ng/ml, p<0.001), and a decline in DNase activity (85% vs. 66%, p<0.001). NET trajectories correlated with imaging and clinical outcome measures. Conclusions Increasing NETs and a decrease of DNase activity were observed during the early course after ICH onset and correlated with imaging and clinical outcomes. Conflict of interest Dr. Martinod has received consulting fees from PEEL Therapeutics. She is an inventor on granted U.S. patent US10617742B2 for the methods for treating and preventing neutrophil-derived NET toxicity and thrombosis and granted U.S. patent US11426405B2 on JAK-STAT signaling inhibition preventing NET formation. The other authors have nothing to disclose.