A new method for measuring inhibition of platelet function by nonsteroidal antiinflammatory drugs.

ABSTRACT

Aspirin is widely used to help prevent vascular occlusion caused by atherosclerotic vascular disease. We used a platelet-aggregation assay (PAA) to evaluate the reliability of a proprietary platelet agonist, platelet prostaglandin agonist (PPA), to detect the amount of platelet inhibition induced by four different classes of nonsteroidal antiinflammatory drugs (NSAIDs) with antiplatelet effects. Twenty normal donors were evaluated before and 24 hours after ingestion of 325 mg of aspirin. With 125 micromol/L PPA, the slope of the PPA-PAA curve completely differentiated aspirin-treated from normal platelets. The aspirin platelet slope, 27.9 +/- 2.0 (range 5.5-47), was significantly decreased (P <.001) compared with the findings before administration of aspirin, 75 +/- 3.1 (range 50-125). Additionally, the time elapsed before 50% platelet aggregation (T(50)) with aspirin, 10.1 +/- 0.7 minutes (range 4.7-17), was significantly prolonged (P <.05) compared with the mean time before administration of aspirin (4.2 +/- 0.2 minutes, range 1.7-6.4). Aspirin in a daily dosage of 325 mg for 14 days produced significantly greater inhibition of PPA-PAA than that induced by a single 325-mg dose (P <.001). The long-term platelet-inhibitory effects of aspirin in 9 normal volunteers were evaluated with PPA-PAA 2, 8, 24, 48, 72, and 96 hours after a single dose of aspirin, 81 or 325 mg. Compared with the preaspirin slope, 79.6 +/- 1.9, the maximal decrease in slope occurred after 2 hours for both 81 mg (61.3 +/- 6.7) and 325 mg (12.1 +/- 1.8). The decreased slopes and increased T(50) observed at 2, 8, and 24 hours (P <.001) reflected the greater degree of platelet inhibition with 325 mg than with 81 mg aspirin. Inhibition of PPA-PAA was observed with nonaspirin nonsteroidal antiinflammatory drugs (NNSAIDs), but, compared with aspirin, the inhibition was minimal. PPA-PAA may be used to help measure the magnitude of NSAID-induced inhibition of platelets.