J Thromb Haemost. 2026 Jun 27:S1538-7836(26)00413-7. doi: 10.1016/j.jtha.2026.06.028. Online ahead of print.
ABSTRACT
BACKGROUND: Neutrophil extracellular traps (NETs) are key mediators of immunothrombosis that link 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 NETs burden regarding long-term ischemic stroke recurrence remains unclear.
OBJECTIVES: We investigated the association between thrombus NETs content and stroke recurrence in patients undergoing endovascular thrombectomy (EVT).
METHODS: This retrospective analysis of a prospective registry study included patients with acute ischemic stroke who underwent EVT and had thrombi retrieved for histological analysis. Thrombus NETs 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 into the high NETs group based on a predefined cut-off 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 = 0.013). In multivariable Cox analysis, high thrombus NETs content was independently associated with stroke recurrence (hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.18-4.25; p = 0.014). Sensitivity analyses treating NETs content as a continuous variable confirmed a linear association with recurrence risk (p < 0.001).
CONCLUSIONS: High NETs burden within retrieved thrombi was associated with an increased risk of long-term ischemic stroke recurrence. These findings suggest that thrombus-level NETs content reflects an underlying thromboinflammatory phenotype linked to recurrent ischemic events.
PMID:42364877 | DOI:10.1016/j.jtha.2026.06.028

