INFLUENCE OF ASPIRIN ON HUMAN MEGAKARYOCYTE PROSTAGLANDIN SYNTHESIS

To evaluate whether currently popular aspirin regimens have an effect on the prostaglandin synthesis in human megakaryocytes we measured thr omboxane B2 (TXB2) synthesis in response to thrombin stimulation in hu man megakaryocytes ex vivo. Human megakaryocytes were purified by Coun terflow Centrifugal Elutriation from bone marrow punctures, taken from volunteers before and 2 hours after ingestion of one dose of 500 mg ( n = 4), 80 mg (n = 4) or 40 mg (n = 2) aspirin. Subsequently, megakary ocytes were purified before and 12 h after ingestion of 80 mg (n = 3) aspirin twice daily for 1 week and 12 h after 500 mg (n = 3) aspirin. On average, 140 +/- 102 x 10(3) (mean +/- 1 SD) megakaryocytes were re covered. We found that aspirin inhibits megakaryocyte cyclooxygenase i n a dose-dependent manner. Two hours after 500 mg of aspirin, TXB2 syn thesis in megakaryocytes was inhibited by 96.8 +/- 2 %, whereas one do se of 80 and 40 mg aspirin showed an inhibition of 79.4 +/- 13.7 % and 80 +/- 6.2 % respectively. However, the inhibition of TXB2 synthesis seems not to be long-lasting since, 12 h after the ingestion of aspiri n, an increase of megakaryocyte TXB2 production could be observed whic h reached significance after the 500 mg aspirin dosage (p < 0.048). We conclude that human megakaryocyte cyclooxygenase is sensitive to aspi rin inhibition and that low doses of aspirin (40 and 80 mg) enter the systemic circulation and are able to inhibit megakaryocyte cyclooxygen ase, but this inhibition is incomplete and megakaryocyte cyclooxygenas e seems to recover within 12 h after ingestion of aspirin.