Neutrophil extracellular traps in retrieved thrombi and functional outcome after stroke thrombectomy.

Abstract

Objective: To investigate the association between neutrophil extracellular traps (NETs) content in retrieved thrombi and 90-day functional outcomes in patients with acute ischemic stroke (AIS) secondary to anterior circulation large vessel occlusion (LVO) undergoing mechanical thrombectomy (MT).

Methods: This retrospective study analyzed data from a prospectively maintained cohort of 129 consecutive AIS patients who underwent MT at West China Hospital between January 2023 and October 2024. Retrieved thrombi were stained for citrullinated histone H3 (CitH3) and myeloperoxidase (MPO) using immunofluorescence, and the percentage of positive area was quantified to represent NETs content (% area). Patients were dichotomized into high-NETs and low-NETs groups based on an optimal cutoff determined by receiver operating characteristic (ROC) curve analysis for predicting poor outcome (modified Rankin Scale [mRS] score 3-6). The primary endpoint was functional independence (mRS 0-2) at 90 days. Multivariable logistic regression was employed to identify independent predictors of outcome.

Results: The ROC analysis yielded an AUC of 0.644. The optimal cutoff value of defining high NETs content was 2.01%. Among 129 patients (mean age 67.9 years, 48.8% male), 88 (68.2%) were in the high-NETs group. Baseline characteristics were largely comparable, though the high-NETs group had significantly higher admission blood glucose (7.9 vs. 6.7 mmol/L, p = 0.009) and a greater prevalence of atrial fibrillation (65.9% vs. 36.6%, p = 0.002). Despite achieving similarly high rates of successful recanalization (mTICI 2b-3) in both groups (96.6% vs. 97.6%, p = 0.99), patients in the high-NETs group had a significantly lower rate of 90-day functional independence (35.2% vs. 68.3%, p < 0.001). After adjusting for confounding variables, high thrombus NETs content remained a robust independent predictor of a lower likelihood of achieving a good outcome (adjusted Odds Ratio [aOR] = 0.60, 95% CI 0.43-0.84, p = 0.003), along with higher baseline NIHSS (aOR = 0.90, 95% CI 0.84-0.97, p = 0.007) and an increased number of retrieval attempts (aOR = 0.66, 95% CI 0.46-0.96, p = 0.028).

Conclusion: Quantitative assessment of NETs in retrieved thrombi may serve as an accessible biomarker to identify patients at high risk of poor functional recovery despite successful recanalization. However, the predictive performance was only moderate (ROC AUC = 0.644). Moreover, infarct core volume was not assessed and thus not incorporated into the statistical models, which may limit interpretation and generalizability. Prospective multicenter validation and studies incorporating infarct core volume are warranted, together with exploration of NET-targeted adjunctive therapies.