Impaired Thromboxane Production by Newly Formed Platelets after Aspirin Administration to Thrombocytopenic Rats

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Abstract
The in vivo inhibitory effect of aspirin on platelet cyclooxygenase is irreversible and lasts for the entire platelet life span. Reappearance of cyclooxygenase activity in blood after aspirin was proposed as a measure of the formation of new platelets and as an indirect indicator of platelet survival. A delay of 24-72 h in recovery, however, was observed and aspirin might also inhibit megakaryocyte cyclooxygenase. To test this possibility, aspirin (100 mg/kg) or saline were administered i.p. to rats made thrombocytopenic 2 h later (platelet count less than 5% of basal value) by a specific antiplatelet antiserum. Malondialdehyde (MDA) and thromboxane B2 (TxB2) production by platelets was measured by spectrophotometry and radioimmunoassay, respectively, during the period of platelet count restoration. By 24 h after thrombocytopenia was induced, platelet count was about 15% of basal values in control and aspirin-treated rats. While in controls MDA and TxB2 production was restored to about 20% of basal values, in aspirin-treated rats less than 5% return of activity was detected. A marked difference between the 2 groups was still found 96 h after induction of thrombocytopenia, when platelet count restoration was similar. Since aspirin disappeared very rapidly from the circulation, the delay in recovery of cyclooxygenase activity supports the hypothesis of a megakaryocyte effect of this drug.