and In Vivo

plasminogen activator inhibitors (PAls) provides a major regulatory mechanism for the fibrinolytic capacity. In plasma, PAI-l (endothelial-type plasminogen activator inhibitor) is the primary inhibitor of tissue plasminogen activator and urokinase’8 when these plasminogen activators are present at low concentrations. PAI-2 (placental-type PAl) is usually not found in plasma except during pregnancy.9 Other plasma serine protease inhibitors (eg, alpha-2 antiplasmin, antithrombin III, and alpha-2 macroglobulin) have also been described to interact with plasminogen activators.6’#{176}’3 These inhibitors, however, react with tissue-type plasminogen activator (tPA) and urokinase with much lower rate constants than PAl- 1 #{149}7�2�3 Although the plasma concentrations of these inhibitors are higher than that of PAl-i,’3 they are thought to play a role for plasminogen activator inhibition only when the concentration of plasminogen activators exceeds the inhibitory capacity of PAl-I.’3 Recently an additional, heparin-dependent inhibitor of urokinase has been demonstrated in plasma and urine’s which was designated PAI-3.’5 We have shown that PAI-3 is immunologically identical to the heparin-dependentinhibitor of activated protein C (PCI),’6 originally described by Marlar et