ANTIPLATETLET DRUGS - DO THEY AFFECT MEGAKARYOCYTES

Anti-platelet drugs are used in clinical medicine to prevent thromboem bolic complications of cardiovascular diseases, Among anti-platelet dr ugs, very little is known of their possible effects on megakaryocytes. ASA is the only compound for which it has clearly been demonstrated t hat its mechanism of action involves acetylation of the Ser 529 residu e in cyclo-oxygenase in platelets and megakaryocytes. Because megakary ocytes possess membrane receptors for ADP, the thienopyridine metaboli tes of ticlopidine and clopidogrel may modify these receptors as in pl atelets and hence prevent ADP binding and further activation. Megakary ocytes also have GPIIb-IIIa receptors for the adhesive protein fibrino gen and may be accessible in vivo to GPIIb-IIIa antagonists such as th e monoclonal antibody abciximab. Drugs such as heparin or the phosphod iesterase inhibitor anagrelide can either inhibit or stimulate megakar yocytopoiesis and platelet production, while cytokines such as thrombo poietin affect megakaryocytopoiesis, platelet production and platelet function by potentiating the activation of platelets by other agonists .