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It is generally accepted that there is no correlation between aspirin (ASA) dosage and antithrombotic effect. This hypothesis was tested by devising an animal model of thrombosis consisting of an A-V shunt with flow rate controlled at 200 ml/sec. The occlusion time (T-O) was found to be dependent upon formation of a platelet rich thrombus confirmed by electron microscopy. Three groups of dogs (4 in each group) were treated with 3 dosages of ASA (160, 325, and 650 mg BID for 4 days) and mean T-O under treatment was divided by mean T-O during a control period to obtain an Index of prolongation of T-O by ASA in each animal. The mean indexes of prolongation for the groups were 1.31±0.14 (160 mg), 1.41±0.12 (325 mg), and 2.67±0.32 (650 mg), with the last being significantly greater (p <.01) than the others. This paralleled the salicylate levels: 1.0±0.37 (160 mg), 1.75±0.31 (325 mg), and 4.98±0.53 mg/dl (650 mg). The index of prolongation T-O for each animal was correlated with ASA dosage in mg/kg (r=0.86, ऩ <.001) and salicylate levels (r=0.77, p <.01). To confirm a dosage effect, 3 animals were treated with low (160 mg BID) and high (650 mg BID) dose ASA. In each animal, T-O (sees.) was significantly longer (p <.001) with the higher dose. ASA in all doses produced equivalent suppression of collagen-induced aggregation, 14C-serotonin release, and platelet prostaglandin synthesis as measured by thrombin-stimulated malonyldialdehyde production. These results suggest an antithrombotic dose dependency of ASA not apparent from in vitro platelet function tests.

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