1 The effect on platelet functions of dipyridamole (a pyrimido‐ pyrimidine compound) was compared with a control group of patients taking warfarin. 2 Adhesion, aggregation and platelet factor 4 availability showed a significant decrease in the dypyridamole group. 3 Aggregation and platelet factor 4 showed a significant correlation with blood dipyridamole level. 4 Adhesion, aggregation and platelet factor 4 were reduced below the lower limit of normal at blood dipyridamole levels above 3.5 micronmol/1.

1 In normal volunteers maximum reductions in platelet functions, collagen aggregation, adhesion and PF4 availability, were achieved using combined doses of 50 mg three times daily dipyridamole + 180 mg ASA or 75 mg three times daily dipyridamole + 120 mg ASA daily. 2 These doses did not prolong the bleeding time. 3 A synergistic effect has been demonstrated with 25 mg dipyridamole three times daily and 60 mg ASA. 4 At higher doses the effects on platelet functions were additive up to the maximal response. 5 The effect of low doses of ASA on platelet function was cumulative. 6 As lower doses of ASA in the combination studied inhibit platelet functions maximally without altering the bleeding time and probably without inhibiting prostacyclin, we suggest that these combinations of dipyridamole and ASA merit consideration in future clinical trials.

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.

The effect of Acetyl Salicylic Acid (ASA), Dipyridamole (DPM) and in combinations on the response of platelets to woven Dacron perfused in an artificial circulation was investigated. Circuits were perfused by heparinised blood donated by 6 volunteers after each had taken: -1) No drugs 2) ASA 300mg tds 3) DPM 100mg qds 4) ASA 300mg + DPM 75mg tds 5) ASA 80mg + DPM 75mg tds 6) ASA 80mg tds, for 1 week. Bleeding times were performed prior to each donation. Platelet functions were estimated during perfusion. Each grafts surface was examined by scanning electron microscopy (SEM) at the end of perfusion.Platelet inhibition by low dose ASA + DPM was accompanied by less extension of bleeding time, and we suggest that such combination may protect patency in Dacron grafts at risk.