N-Acetyl Cysteine Prevents Arterial Thrombosis in a Dose-Dependent Manner In Vitro and in Mice.
Level 5 - mechanism / opinion, no new human data
Bench and animal research (in vitro human blood assay and mouse model)
PubMed 38126172 · doi:10.1161/ATVBAHA.123.319044
What was done
Researchers evaluated N-acetyl cysteine (NAC) as an antithrombotic agent targeting von Willebrand factor (VWF). In vitro, platelet accumulation rate and occlusion time were tested in human whole blood using a microfluidic model of arterial thrombosis. In vivo, acute clot formation, clot stability, and tail bleeding time were assessed in mice using a modified Folts model, alongside evaluations at 6 hours post-dose and after multiple injections to assess persistence and cumulative effects.
What was found
In vitro, human whole blood treated with 3 mmol/L or 5 mmol/L NAC delayed thrombus formation 2.0-fold and 3.7-fold compared to control, respectively (P < 0.001); 10 mmol/L NAC prevented occlusive clot formation entirely with no visible macroscopic platelet aggregation (P < 0.001). In vivo, 400 mg/kg NAC prevented occlusive clots in mice without significantly altering tail bleeding times. Lower doses significantly reduced clot stability, and multiple injections produced a persistent and cumulative reduction in clot stability even after clearance from the blood (P < 0.001).
Why it matters
Standard antiplatelet therapies increase major bleeding risk. These preclinical findings demonstrate that targeting VWF with NAC reduces arterial thrombus formation in models without substantially prolonging bleeding time, suggesting an alternative antithrombotic approach.
Limits
Findings are restricted to preclinical in vitro human blood assays and murine models, and cannot establish clinical efficacy or safety in humans. The abstract does not disclose the sample sizes (n) for blood donors or mice, nor exact values for the lower dose tested.
Cited by
- supports N-acetylcysteine (NAC) inhibits von Willebrand factor to prevent microclots.