Influence of intravenously administered acetylsalicylic acid on platelet functions. A pharmacodynamic and pharmacokinetic study.

Abstract

The influence of intravenously administered acetylsalicylic acid (ASA) on the kinetics of platelet function was examined in 10 patients. Simultaneously, assays of salicylate in plasma were performed. A significant inhibition of platelet aggregation as well as PF 3 and PF 4 availabilities could be demonstrated 2 min after injection. A decrease of platelet adhesion was significant after 15 min. The inhibition of platelet functions was still present after 24 h and was partially demonstrable after 72 h. The concentration of salicylate in plasma 2 min after injection of ASA was only about two thirds of the level calculated from mere distribution in circulation. After 1 h, half of the initial salicylate had disappeared from plasma. No salicylate could be found after 24 hours. ASA also depressed platelet functions when added to platelet-rich plasma in vitro in a concentration of 100 mug/ml. Inhibition of platelet aggregation and of PF 4 availability were dependent on the time of incubation. Their onset was much slower in vitro than in vivo. No inhibition of the PF 3 availability could be found in vitro. The inhibition of platelet functions by ASA is demonstrable almost immediately after injection while the duration of this inhibition is considerably longer than the elimination time of salicylate from plasma. This allows the conclusion that a direct intravascular reaction between ASA and platelets occurs and that the inhibition of platelet functions is irreversible.