Platelets and thrombolysis: Cooperation or contrariety?

Fibrinolytic therapy is the established treatment for the management of patients with ST elevation acute myocardial infarction (AMI). Present thrombolytic regimens have a number of limitations, including the failure to produce early and sustained reperfusion, as well as an inability to prevent reocclusion in at least some patients. Platelets play an important role in coronary thrombosis responsible for AMI. The effect of coronary thrombolysis on platelets has been extensively debated in the literature, with controversial evidence of both platelet activation and inhibition. Among fibrinolytic agents, tissue plasminogen activator (t-PA) is considered to be the cornerstone in the treatment of acute coronary occlusion. The native t-PA molecule has been modified in an attempt to achieve improved lytic characteristics with less risk of bleeding events. Extensive research has led to a group of mutant t-PA variants referred to as third-generation plasminogen activators. TNK-t-PA is one bioengineered variant of t-PA; another is reteplase (r-PA). They have been developed to establish more rapid, complete and stable coronary artery patency, thus promising reduced mortality. Both r-PA and TNK-t-PA are effective when given as bolus therapy, a feature that may facilitate earlier treatment initiation as well as lower treatment costs. New acute coronary treatment regimens include potent antiplatelet agents on top of thrombolysis that may improve sustained reperfusion. This review summarizes the latest and often contradictory data on the interaction between fibrinolytic therapy and platelets in certain in vitro, animal and clinical scenarios.