Association between thrombus neutrophil extracellular trap content and ischemic stroke recurrence

Abstract

Background

Neutrophil extracellular traps (NETs) are key mediators of immunothrombosis, linking inflammation and coagulation. Although the presence of NETs within retrieved thrombi has been associated with unfavorable procedural and short-term functional outcomes after ischemic stroke, the prognostic significance of thrombus NET burden for long-term ischemic stroke recurrence remains unclear.

Objectives

We investigated the association between thrombus NET content and stroke recurrence in patients undergoing endovascular thrombectomy.

Methods

This retrospective analysis of a prospective registry study included patients with acute ischemic stroke who underwent endovascular thrombectomy and had thrombi retrieved for histological analysis. Thrombus NET content was quantitatively assessed using immunohistochemistry. The primary endpoint was recurrent ischemic stroke during follow-up.

Results

Among 452 included patients (mean age, 73.2 years; 51.5% male), 104 (23.0%) were classified as the high NETs group based on a predefined cutoff value. During a median follow-up of 29.2 months, 41 patients (9.1%) experienced recurrent ischemic stroke. The high NETs group demonstrated a significantly higher cumulative incidence of recurrence (log-rank P = .013). In multivariable Cox analysis, high thrombus NET content was independently associated with stroke recurrence (hazard ratio, 2.24; 95% CI, 1.18-4.25; P = .014). Sensitivity analyses treating NET content as a continuous variable confirmed a linear association with recurrence risk (P < .001).

Conclusion

High NET burden within retrieved thrombi was associated with an increased risk of long-term ischemic stroke recurrence. These findings suggest that thrombus-level NET content reflects an underlying thromboinflammatory phenotype linked to recurrent ischemic events.