The Effects of Aspirin on Megakaryocyte Prostaglandin Production

Aspirin inhibits the enzyme cyclooxygenase in platelets by irreversibly acetylating it. Since platelets are derived from the fragmentation of megakaryocyte cytoplasm and contain similar organelles and enzymes, we attempted to study the inhibitory effect of aspirin on the prostaglandin synthesis of isolated rat megakaryocytes. Megakaryocytes were isolated from rat bone marrow using cellular velocity sedimentation in an isokinetic Ficoll gradient. The isolated megakaryocytes were found capable of significant prostaglandin E synthesis as measured by radioimmunoassay when exposed to N-ethylmaleimide (NEM). Aspirin pretreatment in vivo abolished the ability of rat megakaryocytes to synthesize prostaglandin E. It seems likely that aspirin can also acetylate irreversibly the megakaryocyte cyclooxygenase enzyme and that this defect is carried over to the newly formed platelets. The implications of these results may significantly influence the dose schedules of antiplatelet drugs currently being used in clinical trials.