Effect of dipyridamole alone and in combination with aspirin on whole blood platelet aggregation, PGI₂ generation, and red cell deformability ex vivo in man

Study objective - The aim was to investigate the effects of dipyridamole, aspirin, and a combination of dipyridamole plus aspirin on platelet aggregation in whole blood, PG1₂ generation, and red cell deformability ex vivo.
Subjects - were 16 male volunteers, aged 22-39 years, mean age, 26.6 years.
Design - This was a randomised, double blind, placebo controlled trial. The volunteer received each of the following treatments 10 days apart: dipyridamole 200 mg; aspirin 300 mg; dipyridamole 200 mg plus aspirin 300 mg; matched placebos.
Measurements and main results -Blood was taken for platelet function tests, PGI₂ metabolite assay, and red cell deformability before and 2 h after the trial dose was taken. Platelet aggregation was quantified by measuring the fall in single platelet count after stimulation with 2 µg.ml^-1 collagen or 50 nM platelet activating factor (PAF), or by rollermixing aliquots of blood to initiate spontaneous aggregation.  The platelet function tests were completed at 37°C within 10 min of venepuncture. The stable metabolite of PG1₂, 6-keto PGF_1a, was measured in
serum. There was inhibition of spontaneous platelet aggregation by dipyridamole (p<0.004), aspirin (p<O.005), and the combination of dipyridamole plus aspirin (p<O.OOO1) as compared with placebo.  PAF induced platelet aggregation was inhibited by dipyridamole (p<0.002) and the combination of dipyridamole plus aspirin (p<O.OOO1) but aspirin alone had no inhibitory effect. Collagen induced
platelet aggregation was inhibited by all three treatments: dipyridamole (p<O.O6), aspirin (p<O.OOO1), and the combination of dipyridamole plus aspirin
(p<O.OOO1). PG1₂ generation was markedly inhibited by aspirin (p<O.OOO1) and the combination doses (p<O.OOO1) but was unaffected by dipyridamole alone. Of the three active treatments, only dipyridamole alone significantly (p<O.OO1) increased red cell deformability; there was a modest decrease in red cell deformability with aspirin.
Conclusions - The results with PAF support the view that dipyridamole inhibits platelet activation by more than one mechanism; the effect on collagen
induced and spontaneous platelet aggregation suggests that the effect of the combination doses is additive and that on red cell deformability the synergy is negative.