What is the mechanism by which alteplase activates fibrin-bound plasminogen?

Alteplase, known as tissue plasminogen activator (tPA), functions primarily by catalyzing the conversion of fibrin-bound plasminogen to plasmin. This action is particularly effective in the presence of fibrin, as alteplase binds to the fibrin molecules in a thrombus (blood clot) and activates the plasminogen that is specifically associated with that fibrin. This process results in localized fibrinolysis, which is the breakdown of the thrombus, allowing for the restoration of blood flow.

The activity of alteplase is crucial because it selectively activates the plasminogen that is bound to fibrin rather than free plasminogen circulating in the plasma. This selectivity ensures that the fibrin clots are targeted for degradation while minimizing the risk of systemic bleeding by reducing the activation of free plasminogen. Therefore, the rapid activation of fibrin-bound plasminogen by alteplase is a key characteristic of its mechanism of action, making it effective for therapeutic use in conditions such as acute myocardial infarction and ischemic stroke.