Theophylline inhibits platelet aggregation, prostaglandin and thromboxane production by a mechanism which is independent of cyclic AMP.

Theophylline (0.05-1.0 mM) greatly enhanced the inhibition of platelet aggregation by prostaglandin E1 and at higher concentrations (1.0-4.0 mM) theophylline alone inhibited platelet aggregation, by a mechanism which did not involve significant changes in platelet cAMP levels. These concentrations of theophylline and theophylline in combination with prostaglandin E1, inhibited the synthesis of thromboxane A2, prostaglandin E2 and F2a in stimulated platelets. Theophylline also inhibited arachidonic acid-stimulated platelet aggregation suggesting an effect on cyclooxygenase activity. The calcium ionophore A23187 prevented and reversed the inhibition of platelet aggregation by theophylline, suggesting that theophylline inhibits the rise in intracellular calcium levels which occurs in response to the synthesis of prostaglandin endoperoxides and thromboxane A2.