Abstract
It is now widely agreed that platelets are intimately involved in and contribute to the pathogenesis of acute coronary thrombosis. Aspirin, a relatively weak inhibitor of platelet activation, saves lives when administered early after acute myocardial infarction and should be routinely used as lifelong therapy in patients with coronary atherosclerosis. Ticlopidine has a mechanism of action distinct from and additive to that of aspirin; it inhibits activation of platelets mediated by the agonist, adenosine diphosphate (ADP). The reduction in subacute coronary thrombosis attained by the use of combination therapy with aspirin and ticlopidine (for 2–4 weeks) after intracoronary stenting is further evidence of the role of platelets in mediating acute arterial thrombosis. Potent platelet agonists (like thrombin) can override the effect of aspirin and ticlopidine; therefore these agents are of limited efficacy. In contrast, inhibitors of the platelet glycoprotein (GP) IIb/IIIa receptor are potentially more potent inhibitors of adhesive platelet interaction and may therefore be effective in blocking adhesive platelet interactions irrespective of the activating agonist. The GPIIb/IIIa receptor mediates the bridging of platelets (platelet aggregation) via fibrinogen, thus allowing platelet to bind other platelets at the injured vessel wall. Antagonists of this receptor are thus capable of blocking the “effector function” by acting at a step that is downstream to platelet activation. By abrogating the final common pathway of platelet aggregation, antagonists of GPIIb/IIIa also affect the most proximal step in thrombin generation (that most efficiently occurs on the membrane surface provided by platelets). Accordingly, these agents can profoundly inhibit arterial thrombosis. The clinical use of the antibody fragment directed against the GPIIb/IIIa receptor (c7E3 Fab) has truly revolutionized the practice of interventional cardiology and has the potential to effectively treat heparin‐resistant intracoronary thrombosis. Synthetic antagonists of fibrinogen binding to the GPIIb/IIIa receptor (the “fibans”) are currently under initial clinical testing.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have