Inhibition of plasmin by antithrombin-heparin complex. II. During thrombolytic therapy in man

The role of antithrombin as an inhibitor of plasmin in the presence and absence of heparin was studied during thrombolytic therapy in 12 patients with vascular occlusive disease. The extent of plasmin-antithrombin-(heparin) complex formation was studied by intravenous injection of iodine-labelled antithrombin (5-20 muCi) and quantitation of the amount of antithrombin bound to plasmin. In the absence of heparin, less than 0.8% of the labelled antithrombin was recovered in the plasmin-antithrombin complex but between 1.2 and 4.8% following injection of 5000 iu of heparin. Thus only between 3 and 11% of the in vivo formed plasmin is neutralized by antithrombin-heparin complex. Repeated activation of the fibrinolytic system resulted in a shortening of the plasma radioactivity half-life of labelled antithrombin from 2.45 to 2.03 d in the absence of heparin (three patients), and from 3.13 to 2.35 d following heparin administration (two patients). This increased turnover does not result in a decrease of the plasma antithrombin level.