9 Anti-platelet drugs: do they affect megakaryocytes?

Anti-platelet drugs are used in clinical medicine to prevent thromboembolic complications of cardiovascular diseases. Among anti-platelet drugs, very little is known of their possible effects on megakaryocytes. ASA is the only compound for which it has clearly been demonstrated that its mechanism of action involves acetylation of the Ser 529 residue in cyclo-oxygenase in platelets and megakaryocytes. Because megakaryocytes possess membrane receptors for ADP, the thienopyridine metabolites of ticlopidine and clopidogrel may modify these receptors as in platelets and hence prevent ADP binding and further activation. Megakaryocytes also have GPIIb-IIIa receptors for the adhesive protein fibrinogen and may be accessible in vivo to GPIIb-IIIa antagonists such as the monoclonal antibody abciximab. Drugs such as heparin or the phosphodiesterase inhibitor anagrelide can either inhibit or stimulate megakaryocytopoiesis and platelet production, while cytokines such as thrombopoietin affect megakaryocytopoiesis, platelet production and platelet function by potentiating the activation of platelets by other agonists.