The Inhibition of Plasmin by Antithrombin–Heparin Complex

Summary. Human plasma, containing increasing amounts of heparin (0‐125 iu/ml) and highly purified biologically intact131 I‐labelled antithrombin was activated with 2000 CTA units of urokinase per ml, which resulted in complete activation of the fibrinolytic system. The plasmin‐antithrombin‐(heparin) complex formed was isolated and quantitated. In the absence of heparin only 0.4 ± 0.1% of the plasma antithrombin was bound to plasmin. In the presence of heparin it was: 0.9±0.1% with 1 iu/ml, 1.5±0.7% with 2 iu/ml, 2.5±0.8% with 5 iu/ml, 3.8 ± 0.5% with 25 iu/ml and 4.7±1.0% with 125 iu/ml. Thus antithrombin–heparin complex seems to play a very limited role in the inactivation of plasmin under physiological conditions and therapeutic levels of heparin. In plasma depleted of antiplasmin, the fast‐reacting plasmin inhibitor, 1.6–2.1 % of antithrombin was bound to plasmin in the absence of heparin, and 8.2‐10% in the presence of 25 iu heparin/ml. In plasma depleted both of antiplasmin and α2‐macroglobulin, 8.1–8.6% of antithrombin bound to plasmin in the absence of heparin and 16–21 % in the presence of 25 iu of heparin/ml. However, since the molar concentration of plasminogen in plasma is approximately half that of antithrombin, the relative amount of plasmin neutralized by antithrombin is twice as high.