Key result
Desmopressin acetate reverses DAPT-induced platelet dysfunction, driven by reduced hepatic PRDX5 expression.
Why the study?
Desmopressin acetate has been proposed to reverse antiplatelet-induced platelet dysfunction during life-threatening hemorrhage, but its efficacy and mechanisms remain incompletely understood.
Does desmopressin acetate restore platelet and coagulation function impaired by dual antiplatelet therapy, and what are the underlying redox and metabolic mechanisms?
Does desmopressin acetate restore platelet and coagulation function impaired by dual antiplatelet therapy, and what are the underlying redox and metabolic mechanisms?
This translational study identifies a novel hepatic PFKFB3-glycolysis-ROS-PRDX5 signaling axis through which desmopressin acetate reverses dual antiplatelet therapy-induced platelet dysfunction, supporting its potential utility for urgent hemostatic rescue.
Animal data link desmopressin to DAPT platelet rescue via PFKFB3-ROS-PRDX5; hypothesis-generating for human hemostasis.
JOURNAL/mgres/04.03/01612956-990000000-00084/figure1/v/2026-03-26T165950Z/r/image-tiff Antiplatelet therapy is extensively used in the prevention and treatment of cardiovascular and cerebrovascular diseases; however, life-threatening hemorrhage requires urgent reversal of platelet dysfunction. Desmopressin acetate has been proposed as a rescue strategy, yet its efficacy and underlying mechanisms remain incompletely understood, particularly regarding redox regulation. A mouse carotid artery blood flow injury model was employed to evaluate the effects of desmopressin acetate on platelet and coagulation dysfunction induced by antiplatelet therapy. Proteomic analyses were performed in both patients and mice to identify differentially expressed proteins. Genetic knockout and pharmacological inhibition approaches were used to investigate the mechanistic pathways involved. Desmopressin acetate effectively restored platelet function and coagulation capacity in antiplatelet-treated mice. Proteomic profiling identified peroxiredoxin-5, a key antioxidant enzyme, as significantly upregulated following antiplatelet therapy but markedly downregulated after desmopressin acetate administration; these findings were validated in plasma samples from 10 patients who received dual antiplatelet therapy for unruptured intracranial aneurysms. Functional studies demonstrated that proteomic profiling identified peroxiredoxin-5 supplementation impaired platelet function, whereas proteomic profiling identified peroxiredoxin-5 knockout or inhibition significantly improved platelet activity. Notably, desmopressin acetate primarily suppressed liver-derived proteomic profiling identified peroxiredoxin-5 expression. Mechanistically, desmopressin acetate enhanced platelet glycolysis via phosphofructokinase-2/ fructose-2,6-bisphosphatase 3 activation, leading to increased intracellular reactive oxygen species levels. Inhibition of phosphofructokinase-2/fructose-2,6- bisphosphatase 3 attenuated glycolysis, reduced reactive oxygen species generation, and restored proteomic profiling identified peroxiredoxin-5 expression, thereby abolishing the platelet-rescuing effects of desmopressin acetate. Desmopressin acetate rescued platelet dysfunction induced by antiplatelet therapy through a glycolysis-reactive oxygen species-proteomic profiling identified peroxiredoxin-5 axis, in which glycolysis-driven reactive oxygen species generation plays a central regulatory role. These findings indicate redox modulation as a critical mechanism underlying desmopressin acetate-mediated platelet rescue and suggest a potential therapeutic strategy for managing severe bleeding associated with antiplatelet therapy.
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Wang et al. (2026) studied Platelet and coagulation dysfunction induced by dual antiplatelet therapy (DAPT) for unruptured intracranial aneurysms (n=397). Desmopressin acetate (DDAVP) vs. Pre-DDAVP baseline in self-controlled patient cohorts; vehicle or DAPT alone in mouse and cell models was evaluated on Restoration of platelet function (AA and ADP channel inhibition via thromboelastography/aggregometry), carotid artery occlusion time, and hepatic/serum peroxiredoxin-5 (PRDX5) expression (p=0.0065). Desmopressin acetate restored DAPT-induced platelet dysfunction and significantly reduced hepatic PRDX5 expression (P=0.0065) via PFKFB3-driven glycolysis and ROS generation.
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