The roles of alpha 2-antiplasmin and plasminogen activator inhibitor 1 (PAI-1) in the inhibition of clot lysis.

The relative importance of the two major inhibitors of fibrinolysis, alpha 2-antiplasmin (alpha 2-AP) and plasminogen activator inhibitor (PAI-1), were investigated using a simple microtitre plate system to study fibrin clot lysis in vitro. Cross-linked fibrin clots contained plasminogen and tissue plasminogen activator (t-PA) at concentrations close to physiological. Purified alpha 2-AP and PAI-1 caused dose-dependent inhibition. All the inhibition due to normal plasma, either platelet-rich or poor, was neutralised only by antibodies to alpha 2-AP. Isolated platelets, at a final concentration similar to that in blood, 2.5 x 10(8)/ml, markedly inhibited clot lysis. This inhibition was neutralised only by antibodies to PAI-1. At the normal circulating ratio of plasma to platelets, alpha 2-AP was the dominant inhibitor. When the platelet:plasma ratio was raised some 20-fold, platelet PAI-1 provided a significant contribution. High local concentrations of PAI-1 do occur in thrombi in vivo, indicating a role for PAI-1, complementary to that of alpha 2-AP, in such situations.