Effect of aspirin and sodium salicylate on thrombosis, fibrinolysis, prothrombin time, and platelet survival In rabbits with indwelling aortic catheters.
We have studied the effect of different doses of aspirin on platelet function, PGI2 formation, platelet survival, thrombosis, fibrinolysis, and prothrombin time in rabbits with indwelling aortic catheters. The thrombi formed around indwelling aortic catheters were found to have a large fibrin component, and their formation was inhibited by heparin administration. Thus, in these experiments we examined the effect of aspirin (a weak inhibitor of thrombin-mediated platelet aggregation) under conditions in which thrombin was a major factor in the initiation and growth of the thrombi. Only very high doses of aspirin tended to inhibit thrombus formation over the 5-day period of observation, and a statistically significant inhibition of thrombus formation was produced by equivalent concentrations of sodium salicylate. The failure of high doses of aspirin to achieve a significant inhibition of thrombosis under the conditions of these experiments (whereas an equivalent dose of sodium salicylate was inhibitory) could be due to aspirin inhibition of PGI2 formation. Shortened platelet survival was not affected by aspirin treatment or the dose sodium salicylate that inhibited thrombus formation. The tendency to inhibit thrombus formation appeared to be unrelated to an effect on platelets but was associated with prolongation of the one-stage prothrombin time and increased whole blood fibrinolytic activity; doses of aspirin that inhibited platelet  aggregation in response to sodium arachidonate or collagen, and PGI2 formation by the vessel wall, did not have a significant effect on the amount of thrombus present at 5 days. However, the high doses of aspirin that inhibited PGI2 formation were associated with a tendency to increased thrombus formation during the first 3 hr after insertion of the catheter. The results of these experiments show that when thrombin is an important factor in the formation of thrombi, aspirin is a weak inhibitor of thrombosis unless doses are used that provide sufficient salicylate to interfere with blood coagulation and promote whole blood fibrinolytic activity. These results also show that thrombus formation can be inhibited without an apparent change in platelet survival.
D000818:Animals; D001011:Aorta; D001241:Aspirin / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets; D002404:Catheterization / Q000009:adverse effects*; D002408:Catheters, Indwelling; D002470:Cell Survival / Q000187:drug effects*; D005342:Fibrinolysis / Q000187:drug effects; D006493:Heparin / Q000627:therapeutic use; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011517:Prothrombin Time; D011817:Rabbits; D012459:Salicylates / Q000097:blood; D012980:Sodium Salicylate / Q000494:pharmacology*; D013927:Thrombosis / Q000517:prevention & control
D012459:Salicylates; D006493:Heparin; D001241:Aspirin; D012980:Sodium Salicylate