Plasmin inhibitors in the prevention of systemic effects during thrombolytic therapy: specific role of the plasminogen-binding form of alpha 2-antiplasmin

Abstract

To delineate the role of plasmin inhibitors, especially the two molecular forms of α₂-antiplasmin (that is, the plasminogen-binding and the nonplasminogen-binding forms), in the control of systemic effects during thrombolytic therapy, the consumption of plasmin inhibitors and the degree of fibrinogen breakdown were studied in 35 patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) or streptokinase.

At a low degree of plasminogen activation (in six patients treated with rt-PA), plasminogen-binding α₂-antiplasmin was consumed first. At a higher degree of plasminogen activation (in 20 patients), plasminogenbinding α₂-antiplasmin became exhausted (<20%) and other plasmin inhibitors (that is, nonplasminogen-binding α₂-antiplasmin and α₂-macroglobulin) were consumed. After extensive plasminogen activation (in nine patients treated with streptokinase), plasminogen-binding α₂-antiplasmin consumption was complete and nonplasminogen-binding α₂-antiplasmin and α₂-macroglobulin were consumed to about 30% to 50% of the pretreatment level. No significant C₁-inactivator consumption occurred, even at extreme degrees of plasminogen activation.

Fibrinogen breakdown as a marker for systemic effects correlated strongly with consumption of plasminogenbinding α₂-antiplasmin. Fibrinogen breakdown did occur, but only when the amount of plasminogen-binding α₂-antiplasmin was decreased to <20% of the pretreatment level. The other plasmin inhibitors could not prevent fibrinogen breakdown. These results were confirmed by in vitro studies.

It is concluded that plasminogen-binding α₂-antiplasmin is the most important inhibitor of plasmin in the circulation. To obtain systemic effects, the amount of plasminogen-binding α₂-antiplasmin, which is a threshold in the circulation, has to be overcome. This indicates that plasminogen-binding α₂-antiplasmin may be a new marker to predict systemic effects during thrombolytic therapy.