Novel Insights into the Dual Anticoagulant and Antiplatelet Potency of Fructose - 1,6 - Diphosphate In Vitro: Precision Inhibition of Coagulation Initiation and Comprehensive Suppression of Platelet Aggregation

Background Fructose-1,6-diphosphate (FDP), a metabolic intermediate widely used in clinical practice for managing ischemic conditions (e.g., myocardial infarction, hemorrhagic shock) due to its cytoprotective and ATP-enhancing properties, has poorly characterized effects on hemostasis. The current study aimed to systematically evaluate its in vitro impacts on coagulation and platelet function to address this knowledge gap. Methods Global hemostasis was assessed via thromboelastography (TEG) using three platforms (Maiketian, Lepu, Dingrun). Coagulation factor activities (II, V, VII, VIII, IX, X, XI, XII) were quantified with Sysmex CS5100. Platelet aggregation in platelet-rich plasma (PRP) from 5 healthy donors was tested with agonists (adenosine diphosphate [5 µmol/L], arachidonic acid [1 mmol/L], collagen [2.5 µg/mL], epinephrine [10 µmol/L]). Dose-response relationships (FDP: 0–6 mg/mL) were analyzed by linear regression. Results FDP prolonged TEG clot reaction time (R-time) concentration-dependently (P < 0.01). At therapeutic concentration (3.71 mg/mL), R-time increased by 21.8% (Maiketian), 48.3% (Lepu), and 34.1% (Dingrun) vs. controls (n=11). FDP inversely correlated with activities of factors V, VII, IX, XI, and XII (r = −0.989 to −0.997, all P < 0.001), but not factors II, VIII, X. FDP also inhibited platelet aggregation dose-dependently (maximal suppression: 94–95% at 6 mg/mL, P < 0.001), with epinephrine-induced aggregation most sensitive. Conclusions FDP exerts dual effects via selective inhibition of coagulation initiation factors and broad suppression of platelet aggregation. Caution is advised in high-risk populations (e.g., coagulation factor deficiencies, antithrombotic therapy). Further studies are needed to evaluate its clinical implications in anticoagulation therapy and bleeding risk.