13.02.5 Fibrinolysis and Fibrinolytics

Fibrinolysis or thrombolysis is the breakdown of clots. The breakdown of clots is a normal process, and is uses plasmin as the active fibrinolytic agent. Plasmin breaks down both the soluble fibrin and the insoluble fibrin (Figure 13.11). When there is excessive clotting and thrombus formation, drugs are used to activate fibrinolysis. Streptokinase activates the plasma form of plasminogen to produce plasmin, whereas alteplase activates the fibrin form of plasminogen, also to form plasmin for fibrinolysis (Figure 13.11).

Figure 13.11 Mechanism of fibrinolytics (Copyright QUT, Sheila Doggrell)

As streptokinase activates the plasma form of plasminogen, it has widespread effects. It will breakdown thrombi, but it will also breakdown clots, where blood vessel repair is taking place. These widespread effects of streptokinase lead to a high incidence of bleeding. Streptokinase is derived from hemolytic streptococci, a streptococci that breaks down blood clots. Streptokinase is quite antigenic, which can lead to allergic reaction, and even severe allergic reaction such as anaphylaxis. Streptokinase is administered intravenously, and to get a good break down of clots, a loading dose is used and this is followed with a maintenance dose.

Alteplase is the generic or non-proprietary name for tissue type plasminogen activator (also known as TPA). It is claimed that alteplase selectively activates fibrin form of plasminogen, which means it will be clot selective. It was initially claimed that would lead to less bleeding than with streptokinase, but bleeding is a common adverse effect with streptokinase and alteplase. Alteplase is prepared by recombinant DNA. Alteplase is administered intravenously, and a loading and then maintenance dose is used to get the maximum effect.

Both streptokinase and alteplase are used to cause the breakdown of clots, and this included the clots causing multiple pulmonary emboli, deep vein thrombosis, acute myocardial infarction, and stroke.