Cold medical gas plasma promotes hemostasis through platelet activation, yet the underlying molecular and functional mechanisms remain incompletely understood. Here, we investigated gas plasma‐induced platelet activation in human whole blood using flow cytometry, transcriptomic profiling, and pharmacological inhibition. Gas plasma exposure induced robust platelet activation and aggregation, accompanied by hemoglobin oxidation and adenosine diphosphate (ADP) release, but without substantial DNA liberation, consistent with selective red blood cell lysis. Transcriptomic analysis revealed significant regulation of 627 genes associated with platelet activation, inflammation, and oxidative stress responses. Pharmacological inhibition implicated Bruton's tyrosine kinase (BTK) and, to a lesser extent, Toll‐like receptor 4 (TLR4) as partial mediators of gas plasma‐driven activation, whereas other signaling pathways were unaffected. Hemoglobin oxidation to methemoglobin occurred linearly with treatment duration and was mediated by gas plasma‐generated short‐lived species. Modulating gas plasma‐generated reactive species outputs could enhance its hemostatic capacity, especially when applied conductively to the treatment target. Finally, gas plasma‐mediated hemostasis and platelet activation and aggregation were preserved in blood of anticoagulated patients medicated with clopidogrel or novel oral anticoagulants. Collectively, these findings demonstrate that gas plasma promotes hemostasis through redox‐ and receptor‐dependent platelet activation, modulated by inflammasome and immune signaling pathways, and can circumvent conventional antiplatelet inhibition, supporting its translational potential as a nonthermal, tissue‐preserving, pro‐hemostatic modality for surgical applications.
Bekeschus et al. (Tue,) studied this question.