The effects of four platelet inhibitors on human platelets using two adhesiveness test systems

Abstract

The effects of the nonsteroidal anti-inflammatory drugs acetylsalicylic acid (ASA), naproxen (Naprosyn®, Syntex), and ibuprofen (Motrin®, Upjohn) and of the phosphodiesterase inhibitor VK 774 upon adhesion of human platelets to collagen fibers and to glass beads were compared after incubation with drug at two concentrations for 5 and 10 min. ASA significantly (p < 0.05−0.01) inhibited platelet adhesion to collagen fibers at the two concentrations (2.65 × 10−4 and 5.05 × 10−4 M) and after 5- and 10-min incubations. Naproxen inhibited adhesion significantly (p < 0.05−0.02) at the lower concentration (2.38 × 10−4 M) and at both incubation times. Ibuprofen did not significantly inhibit adhesion to collagen fibers. VK 774 significantly (p < 0.05−0.005) inhibited platelet adhesion to collagen fibers at both concentrations (2.38 × 10−4 and 4.54 × 10−4 M) and at both incubation times. ASA (1 × 10−3 M) produced slight but statistically significant (p < 0.05) inhibition of platelet adhesion to glass beads. Ibuprofen and naproxen (1 × 10−3 M) did not significantly inhibit adhesion in this test. VK 774 (1 × 10−3 M), however, significantly [Formula: see text] inhibited platelet adhesion to glass beads, to a greater extent than to collagen fibers. Naproxen (375 mg) was given orally in a single dose to five volunteer subjects. Bleeding time was doubled (p < 0.02) 2 h later and slightly but not significantly prolonged 24 h later. The second wave of platelet aggregation in response to ADP and adrenaline was completely blocked in all subjects 2 h after medication and still absent in one subject 24 h after medication, and higher concentrations of ADP and adrenaline were required to induce the second wave of aggregation in the remaining four subjects (4.2 × 10−6 M ADP and 5.6 × 10−5 M adrenaline in control period and 9.6 × 10−6 M ADP and 11.1 × 10−5 M adrenaline following drug administration). Collagen-induced aggregation was markedly inhibited 2 h after medication. These findings are in contrast with previously reported results with ibuprofen and suggest that naproxen induces greater impairment of hemostasis than does ibuprofen.