Effect of dipyridamole alone and in combination with aspirin on whole blood platelet aggregation, PGI2 generation, and red cell deformability ex vivo in man.
OBJECTIVE
The aim was to investigate the effects of dipyridamole, aspirin, and a combination of dipyridamole plus aspirin on platelet aggregation in whole blood, PGI2 generation, and red cell deformability ex vivo.


METHODS
were 16 male volunteers, aged 22-39 years, mean age, 26.6 years.


METHODS
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.


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 micrograms.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 degrees C within 10 min of venepuncture. The stable metabolite of PGI2, 6-keto PGF1 alpha, was measured in serum. There was inhibition of spontaneous platelet aggregation by dipyridamole (p less than 0.004), aspirin (p less than 0.005), and the combination of dipyridamole plus aspirin (p less than 0.0001) as compared with placebo. PAF induced platelet aggregation was inhibited by dipyridamole (p less than 0.002) and the combination of dipyridamole plus aspirin (p less than 0.0001) but aspirin alone had no inhibitory effect. Collagen induced platelet aggregation was inhibited by all three treatments: dipyridamole (p less than 0.06), aspirin (p less than 0.0001), and the combination of dipyridamole plus aspirin (p less than 0.0001). PGI2 generation was markedly inhibited by aspirin (p less than 0.0001) and the combination doses (p less than 0.0001) but was unaffected by dipyridamole alone. Of the three active treatments, only dipyridamole alone significantly (p less than 0.001) 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.
Saniabadi
A R
AR
Department of Medicine, University of Dundee, Ninewells Hospital, United Kingdom.
Fisher
T C
TC
McLaren
M
M
Belch
J F
JF
Forbes
C D
CD
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000328:Adult; D001241:Aspirin / Q000009:adverse effects / Q000494:pharmacology*; D004176:Dipyridamole / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D004357:Drug Synergism; D011464:Epoprostenol / Q000096:biosynthesis* / Q000097:blood; D004907:Erythrocyte Deformability / Q000187:drug effects*; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D010979:Platelet Function Tests
D010975:Platelet Aggregation Inhibitors; D015121:6-Ketoprostaglandin F1 alpha; D004176:Dipyridamole; D011464:Epoprostenol; D001241:Aspirin