Summary
The relative importance of the two major inhibitors of fibrinolysis, α2-antiplasmin (α2-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 α2-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 α2-AP. Isolated platelets, at a final concentration similar to that in blood, 2.5 ×
108/ml, markedly inhibited clot lysis. This inhibition was neutralised only by antibodies
to PAI-1. At the normal circulating ratio of plasma to platelets, α2-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
α2-AP, in such situations.
