Nikhil Prasad Fact checked by:Thailand Medical News Team Sep 18, 2026 40 minutes ago
Scientists may have uncovered an important reason why clot-busting drugs sometimes fail to reopen blocked brain arteries during acute ischemic stroke. New research suggests that web-like structures released by immune cells can trap key proteins and inhibitors inside blood clots, effectively putting the brakes on fibrinolysis—the process responsible for dissolving fibrin and breaking down clots.
The findings could eventually support a new strategy combining conventional thrombolytic drugs with an enzyme that dismantles these troublesome DNA structures.
Why Clot-Busting Treatment Can Fail
Intravenous thrombolysis (IVT) using tissue plasminogen activator (tPA) can restore blood flow after ischemic stroke, but its effectiveness is particularly limited when a large vessel is blocked. Researchers wanted to determine whether treatment failure occurred because insufficient tPA actually reached the clot or because something inside the thrombus prevented it from working properly.
The team analyzed 205 thrombi retrieved from individual stroke patients undergoing endovascular treatment. Among them, 83 clots were examined for tPA and other components, while 53 were tested for susceptibility to laboratory thrombolysis. Additional thrombi were studied to determine how neutrophil extracellular traps, or NETs, affected fibrinolysis.
Researchers were affiliated with Université Paris Cité and INSERM; Rothschild Foundation Hospital; StrokeLink F-CRIN Research Network; FHU NeuroVasc2030; Laboratory for Vascular Translational Science; CHU Lille; AP-HP Hôpital Bichat-Claude Bernard; Monash University and the Australian Center for Blood Diseases; Hôpital Lariboisière; and Institut Universitaire de France.
tPA Reached the Clots—but Was Being Held Back
A striking finding was that clots from IVT-treated patients contained more than twice the median concentration of tPA: 0.209 nanograms per milligram of thrombus compared with 0.093 in untreated patients. D-dimer levels, indicating fibrin breakdown, were also significantly higher. Plasminogen levels, however, were similar between groups.
This suggests failed treatment was not simply caused by tPA failing to reach the clot. Instead, this
Thailand Medical News report highlights evidence that NETs may create a biochemical barrier preventing available tPA from achieving sufficient fibrinolysis.
NETs are DNA-rich structures released by neutrophils. Researchers found tPA and plasminogen associated with fibrin, leukocytes, and NETs, while important fibrinolysis inhibitors were also retained around these structures.
DNase 1 Appears to Unlock Fibrinolysis
Adding plasminogen alone failed to significantly dissolve retrieved clots. However, combining plasminogen with DNase 1, an enzyme that breaks down extracellular DNA, produced significant thrombus weight loss, with a stronger effect in clots from IVT-treated patients. Greater lysis was also associated with increased D-dimer release.
Further experiments showed DNase 1 released inhibitors including PAI-1, protease nexin-1, and neutrophil elastase from clots. DNase 1 pretreatment also enhanced subsequent clot breakdown by tPA and plasmin, suggesting that removing NETs can restore access to the fibrinolytic machinery.
Conclusion
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The findings suggest NETs may help explain why tPA reaches some stroke clots yet fails to dissolve them effectively. DNase 1 could potentially complement existing thrombolytic treatment, but clinical trials are needed to establish appropriate dosing, safety, delivery, and whether laboratory benefits translate into improved outcomes for stroke patients.
The study findings were published in the peer reviewed journal: Annals of Neurology.
https://onlinelibrary.wiley.com/doi/10.1002/ana.78346 
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