The Anticoagulant Effects Of Ethyl Pyruvate In Whole Blood Samples

Background Ethyl pyruvate (EP), the ethyl ester of pyruvate, has proven antiinflammatory and antioxidative properties. Additionally, anticoagulant properties have been suggested recently. EP, therefore, is a potentially antiatherosclerotic drug. We aimed to investigate whether EP possesses antiplatelet and anticoagulant properties particularly in the physiological environment of whole blood. Methods We investigated the effects of increasing concentrations of EP on platelet function, on the course of clot development, and on standard coagulation times. Additionally, clot ultrastructure using scanning electron microscopy was analysed. Results EP exerted significant antiplatelet actions: i) Impedance aggregometry amplitudes (11.7 +/- 3.0 ohm, 0 mu g/mL EP) dose dependently decreased (7.8 +/- 3.1 ohm, 1000 mu g/mL EP; -33.3%). ATP exocytosis (0.87 +/- 0.24 nM, 0 mu g/mL EP) measured by the luminiscent method dose-dependently decreased (0.56 +/- 0.14 nM, 1000 mu g/mL; -35.6%). ii) Closure times (104.4 +/- 23.8 s, 0 mu g/mL EP) using the Platelet function analyzer were dose-dependently prolonged (180.5 +/- 82.5 s, 1000 mu g/mL EP; +72.9%) using membranes coated with collagen/ADP. iii) Surface coverage (15.9 +/- 5.1%, 0 mu g/mL EP) dose-dependently decreased (9.0 +/- 3.7%, 1000 mu g/mL EP; -43.4%) using the Cone and Platelet analyzer. EP also exerted significant anticoagulant actions: Coagulation times (177.9 +/- 37.8, 0 mu g/mL EP) evaluated by means of thrombelastometry were dose-dependently prolonged (212.8 +/- 57.7 s, 1000 mu g/mL EP; +19.6%). Activated partial thromboplastin times (31.5 +/- 1.8 s, 0 mu g/mL EP) were dose-dependently prolonged (35.6 +/- 2.3 s, 1000 mu g/mL EP; +13.0%). Prothrombin times (0.94 +/- 0.02 INR, 0 mu g/mL EP) were dose-dependently prolonged (1.09 +/- 0.04 INR, 1000 mu g/mL EP; +16.0%). Conclusion We found that EP possesses antiplatelet and anticoagulant properties in whole blood. Together with its proven anti-inflammatory and antioxidative properties, EP is a potentially antiatherogenic drug.