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, a lpha2-antiplasmin (alpha2-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 plasm inogen and tissue plasminogen activator (t-PA) at concentrations close to physiological. Purified alpha2-AP and PAI-1 caused dose-dependent inhibition. All the inhibition due to normal plasma, either platelet-r ich or poor, was neutralised only by antibodies to alpha2-AP. Isolated platelets, at a final concentration similar to that in blood, 2.5 x 1 0(8)/ml, markedly inhibited clot lysis. This inhibition was neutralise d only by antibodies to PAI-1. At the normal circulating ratio of plas ma to platelets, alpha2-AP was the dominant inhibitor. When the platel et:plasma ratio was raised some 20-fold, platelet PAI-1 provided a sig nificant contribution. High local concentrations of PAI-1 do occur in thrombi in vivo, indicating a role for PAI-1, complementary to that Of alpha2-AP, in such situations.