The effect of regular and enteric-coated aspirin on bleeding time, thromboxane, and prostacyclin

Abstract

We compared the effect of different aspirin schedules, dosages, and formulations on various bleeding time parameters including bleeding time, plasma and total blood volume, and levels of the stable metabolites of thromboxane A 2 (TXA 2) and prostacyclin (PGI 2) (respectively, TXB 2 and 6-keto-prostaglandin F 1α (6-keto-PGF 1α)) to determine the optimal dosage and formulation of aspirin to inhibit TXA 2 production while sparing PGI 2. In a randomized, parallel study, 52 healthy male volunteers (62 independent observations) with no history of bleeding disorders were given 80 mg or 325 mg of regular aspirin, or 325 mg of enteric-coated aspirin to ingest daily (14 pills) or every other day (7 pills) for a continuous 14 day period. Bleeding times were performed on day 1 before aspirin, 6 h after aspirin on day 1, and before aspirin on day 14. Bleeding times, plasma volume, and total volume increased significantly from before aspirin to after 6 h and 14 days (p < 0.0001 for all parameters) for all aspirin formulations. For day 1 before aspirin ingestion to 6 h later, both TX and PGI 2 (p < 0.008) decreased significantly. 6 h after ingestion of aspirin on day 1 to day 14, both TX and PGI 2 levels also significantly decreased (p < 0.0001). There was a highly significant decrease in PGI 2 production on every other day aspirin schedules (p = 0.0001) particularly with 80 mg of aspirin, while the decrease in PGI 2 production on daily aspirin was not significant (p = 0.10). The most favourable ratio of 6-keto-PGF 1α to TXB 2 occurred with 80 mg daily. Daily 325 mg regular or enteric-coated aspirin were not significantly different, while every other day regimes gave significantly lower ratios (p = 0.001). The ingestion of aspirin in different doses, formulations, and schedules produced statistically significant parallel changes in the various bleeding time parameters. On the basis of lower gastric toxicity and most favourable PGI 2 to TX ratio, 80 mg of aspirin daily or 325 mg of enteric-coated aspirin daily are to be recommended.