Serum neutrophil extracellular traps (CitH3 and MPO-DNA complexes) measured before intravenous thrombolysis may serve as promising biomarkers associated with early neurological deterioration after intravenous thrombolysis in patients with acute ischemic stroke.
Among acute ischemic stroke patients treated with intravenous thrombolysis, 15.7% developed early neurological deterioration (END) within 24 hours.
Elevated serum CitH3 above 17.67 ng/mL was independently associated with END after intravenous thrombolysis.
Elevated serum MPO-DNA complexes above 79.72 ng/mL were independently associated with END after intravenous thrombolysis.
The association between CitH3 and END was significantly stronger in patients with coronary artery disease or stroke history and in those with D-dimer levels below 0.50 µg/mL.
A significant interaction between smoking status and MPO-DNA was found in relation to END risk.
Neutrophil extracellular traps (NETs) contribute to thrombolytic resistance and the no-reflow phenomenon after acute ischemic stroke, impairing microvascular reperfusion.
This research suggests that measuring specific proteins in the blood before administering clot-dissolving treatment (thrombolysis) in stroke patients can help predict which patients will get worse in the first 24 hours after treatment. The proteins measured — called CitH3 and MPO-DNA complexes — are released by white blood cells (neutrophils) when they form web-like structures called neutrophil extracellular traps (NETs). In a study of 287 stroke patients treated with the clot-busting drug alteplase, about 1 in 6 patients experienced early neurological deterioration, meaning their stroke symptoms significantly worsened within a day of treatment. Patients with high CitH3 levels (above 17.67 ng/mL) were nearly 4 times more likely to deteriorate, while those with high MPO-DNA levels (above 79.72 ng/mL) were more than 5 times more likely to deteriorate. This research suggests that NETs — sticky, web-like structures that neutrophils release — may interfere with how well clot-dissolving drugs work and may block tiny blood vessels in the brain even after treatment. By measuring these biomarkers in a patient's blood before starting thrombolysis, doctors might be able to identify patients at higher risk of early worsening. The associations were especially strong in patients who smoked, had a history of coronary artery disease or prior stroke, or had lower levels of another blood marker called D-dimer. The practical implication of this research is that NETs could represent both a predictive biomarker and a potential treatment target in acute ischemic stroke. If patients at high risk of early neurological deterioration could be identified before thrombolysis using a simple blood test, clinicians might be able to tailor treatment strategies accordingly. However, further research would be needed to determine whether targeting NETs therapeutically can improve outcomes in these high-risk patients.
Pei L, Zhang W, Zhang D, Zhao Z, Zhou Y, Zong C, et al.. (2026). Neutrophil Extracellular Traps Are Associated With Early Neurological Deterioration in Patients With Acute Ischemic Stroke Receiving Intravenous Thrombolysis: A Prospective Cohort Study.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.125.045163