Dual anticoagulant and antiplatelet effects of fructose-1,6-diphosphate in vitro

While fructose-1,6-diphosphate (FDP) has been clinically applied in ischemic conditions, its comprehensive effects on hemostasis remain to be fully elucidated. This in vitro study examined the influence of FDP on coagulation and platelet function using thromboelastography (TEG) across three platforms, coagulation factor assays, and platelet aggregation tests over a concentration range of 0-6 mg/mL. The results revealed that FDP concentration-dependently prolonged TEG R-time (P < 0.01), with an increase of 21.8-48.3% at the clinically relevant concentration of 3.71 mg/mL. Strong inverse correlations were observed between FDP concentration and the activities of factors V, VII, IX, XI, and XII (r = - 0.989 to - 0.997, P < 0.001), whereas factors II, VIII, and X remained unaltered. Furthermore, FDP significantly inhibited platelet aggregation (P < 0.001), nearly abolishing epinephrine- and ADP-induced aggregation at 6 mg/mL under unbuffered conditions. pH-control experiments confirmed that the anticoagulant effects were FDP-specific, while the antiplatelet effects were primarily mediated by FDP with a partial pH-dependent component. These findings demonstrate that FDP possesses dual anticoagulant and antiplatelet properties through selective inhibition of coagulation initiation factors and broad suppression of platelet responsiveness, suggesting potential implications for clinical use in high-risk populations and warranting further investigation.