The Combined Effect of Dipyridamole and Acetyl Salicylic Acid on Platelet Function and Bleeding Time : Evaluation of Dose for the Prophylaxis of Thrombosis

Abstract

The interaction of Dipyridamole (DPM) and Acetyl Salicylic Acid (ASA) on volunteers was investigated. ASA was given in single doses (multiples of 60mg) at 2 week intervals. DPM (multiples of 25 mg) was given tds for 2 days with a single dose of DPM and ASA on the morning of day 3. Bleeding time and platelet functions were performed 2 hours after each dose. ASA 300mg maximally inhibited aggregation, adhesion and PF4 release. Lower doses of ASA gave significant reductions in collagen aggregation at 120 mg, adhesion at 180mg and PF4 at 240mg. DPM 25mg tds produced reductions in collagen aggregation, adhesion and PF4. Maximal inhibition of platelet function without alteration in bleeding time was achieved by 50mg tds DPM + 180mg ASA or 75mg tds DPM + 120mg ASA. Bleeding time was normal with ASA 120mg, 180mg; prolonged at 300mg and 1000mg and tending to be normalised by 2g. Addition of DPM 75mg tds at each dose of ASA made no alteration in bleeding time. There was a cumulative effect of ASA on bleeding time. Combined DPM mg tds and low dose ASA present a balanced anti thrombotic regimen probably both inactivating thromboxane A2 production and enhancing prostacyclin activity. This dose combination is worthy of evaluation as an additional group, in trials.