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To evaluate whether currently popular aspirin regimens have an effect on the prostaglandin synthesis in human megakaryocytes we measured thromboxane B2 (TXB2) synthesis in response to thrombin stimulation in human megakaryocytes ex vivo. Human megakaryocytes were purified by Counterflow 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, megakaryocytes 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 recovered. We found that aspirin inhibits megakaryocyte cyclooxygenase in a dose-dependent manner. Two hours after 500 mg of aspirin, TXB2 synthesis in megakaryocytes was inhibited by 96.8 +/- 2%, whereas one dose 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 aspirin, an increase of megakaryocyte TXB2 production could be observed which reached significance after the 500 mg aspirin dosage (p < 0.048). We conclude that human megakaryocyte cyclooxygenase is sensitive to aspirin inhibition and that low doses of aspirin (40 and 80 mg) enter the systemic circulation and are able to inhibit megakaryocyte cyclooxygenase, but this inhibition is incomplete and megakaryocyte cyclooxygenase seems to recover within 12 h after ingestion of aspirin.

Cyclooxygenase activity in human platelets reappears after ingestion of aspirin as a function of the platelet production rate. In different studies the activity reappeared without delay or with an interval of at least 48 h after stopping the drug. Because inhibition of megakaryocyte cyclooxygenase is the sole likely explanation for a delay we determined thromboxane B2 in human megakaryocytes obtained under local anaesthesia. We found that aspirin does not inhibit human megakaryocytes in vivo but does so in vitro. Therefore, it does not seem likely that there is actually a delay in platelet cyclooxygenase resurgence after aspirin intake. In order to suppress platelet cyclooxygenase constantly, aspirin should be given once or twice a day and not once or twice a week.

In normal males, platelet prostaglandin synthesis as measured by malondialdehyde (MDA) production is blocked by more than 90% after administration of 600 mg of calciumacetylsalicylic acid and by more than 50% after 100 mg. Repeated doses of 100 mg at 12 h intervals progressively decrease MDA production to below 10% of the basic value. Bleeding time increases from 3.38 +/- 0.36 min to 7.73 0.91 min (mean +/- SEM). The data indicate that 12 h 100 mg doses of calciumacetylsalicylic acid (equal to 80 mg of aspirin) adequately inhibit platelet function.