Symposium on thrombolytic therapy

A. S. TODD (Department of Pathology, The University of Dundee) It has been shown that the activator of plasminogen in tissue is concentrated in the endothelium of blood vessels, especially that of veins and venules (Todd, 1959). Recently, by modifying the time and temperature of incubation (4°C for 24 to 48 hours), the histological technique for identifying plasminogen activator ('fibrinolysis autography') has been improved enabling a greater range of activator concentrations to be detected within a single preparation. This modification has now been used in the study of thrombosis. It is found that the endothelium adjacent to thrombus in veins, pulmonary arteries, cardiac atria, and coronary arteries contains activator. In cases where the thrombus has been loosened, activator can be detected on the fibrin surface, and sometimes lines and foci of activator are found buried within the thrombus, apparently trapped after retraction and rethrombosis. A similar distribution of activator can be demonstrated in pulmonary emboli. Most of the coronary thrombi examined were rich in plasminogen activator. It is, therefore, reasonable to assume that plasminogen activator from endothelium in the venous and coronary circulation plays a major part in the loosening of thrombus and the detachment of emboli. The endothelium of thrombosed systemic arteries rarely shows fibrinolytic activity, although foci of activator are found deep within mural thrombi from heart chambers and great vessels, apparently related to leucocytes. The platelet-rich lines of Zahn appear to be resistant to plasmin digestion, thus accounting for their prominence in older thrombi. Coronary and intramyocardial arteries normally show activator in the endothelium, although at lower concentrations than that in veins of comparable size. The degree of fibrinolytic activity seems unrelated to the amount of intimal thickening. Renal arterioles and glomeruli are also active to about the same extent. Experiments with vessels from limbs subjected to ischaemia during amputation show that the arteries can develop activator concentrations equivalent to those found in veins. Thus, fibrinolytic activity in arteries may be controlled by stimuli of metabolic origin related to the efficiency of their blood supply.