Tage Astrup

The fibrin plate method for estimating fibrinolytic activity

Abstract An improved fibrin plate method for the estimation of plasmin and other fibrinolytic enzymes is described. Its high specificity and sensitivity for plasmin and its accuracy and practical advantages are pointed out. With trypsin its sensitivity is 0.02 μg. Armour trypsin (cryst.).

Fibrinogenolysis and Fibrinolysis with Tissue Plasminogen Activator, Urokinase, Streptokinase-Activated Human Globulin, and Plasmin

Summary In the presence of porcine tissue plasminogen activator, fibrinolysis is greatly enhanced in comparison with fibrinogenolysis. In contrast, other activators (UK, SK-activator) and plasmin showed no, or moderate, differences between lysis of fibrinogen and fibrin. The enhanced tissue activator effect is related to the activation of plasminogen. The observations add a specific mechanism of enhancement of fibrinolysis by tissue activator to that caused by the influence of inhibitors. The process may help to enhance localized fibrinolysis following tissue injury without affecting fibrinogen.

An activator of plasminogen in normal urine.

Summary 1. The fibrinolytic agent present in normal urine is a plasminogen activator. 2. This activator is very sensitive to acid reaction but rather stable at neutral and alkaline reaction. 3. It is suggested that the signincance of this physiological activator of plasminogen is to keep the urinary system free from the harmful effects of clotted blood.

Impairment of the Diurnal Fibrinolytic Response in Man EFFECTS OF AGING, TYPE IV HYPERLIPOPROTEINEMIA, AND CORONARY ARTERY DISEASE

Diurnal patterns of plasma euglobulin fibrinolytic activity, estimated by the fibrin plate method, were determined in groups of young normal and older normal subjects, in subjects with type IV hyperlipoproteinemia, and in subjects with coronary artery disease who had normal lipid profiles. The marked diurnal increases in fibrinolytic activity observed in the young normal subjects were significantly reduced in a large percent of the older normal subjects and in most of the subjects with coronary artery disease or type IV hyperlipoproteinemia. Although not conclusive, these findings were compatible with the hypothesis that an impairment in the responsiveness of the fibrinolytic system may be related to the development of coronary artery disease.

Thromboplastic and Fibrinolytic Activity of the Human Aorta

In the thrombogenic theory of the pathogenesis of arteriosclerotic lesions, parietal fibrin deposits in the arteries play a primary role. In an effort to elucidate the hemostatic system in the arterial wall, the thromboplastic activity and the fibrinolytic activity (estimated as plasminogen activator) in the layers of the human aorta have been estimated. The simultaneous presence of high thromboplastic activity and little or no fibrinolytic activity found in the intima and the media suggest that fibrin can easily he deposited after tissue injury and that its eventual removal depends upon the humoral fibrinolytic system in the circulating blood. The observations apparently support the thrombogenic theory.

A Fibrinolytic System in Human iMilk.

Summary 1. Human milk contains varying amounts of an agent, which activates plasminogen to plasmin. 2. Human milk contains considerable amounts of a proactivator, which by addition of streptokinase is transformed into an activator of plasminogen.

Fibrinolytic Activity in Thrombosed Veins

Thrombosis of the femoral vein in rats was produced by the injection of thrombin, serum, or sodium morrhuate into ligated venous segments. The histologic effects were followed during resolution or organization of the thrombus and were correlated with the appearance and localization of fibrinolytic activity as assayed histochemically. Lysis of the venous thrombus began immediately when thrombin or serum had been used. Sites of thrombolysis were related to the presence of endothelial cells of venous origin and containing plasminogen activator. Sodium morrhuate destroyed the fibrinolytically active endothelial cells thus delaying thrombolysis. Recanalization was associated with the presence locally of active endothelial cells, originating presumably in the adjacent normal venous endothelium. These results support previous observations on the vascular origin of the plasminogen activator. They elucidate the role played by the fibrinolytically active endothelium in the resolution of venous thrombi. They also confirm and extend previous observations on the role of fibrinolytic activity in tissue repair.

Blood coagulation and fibrinolysis in tissue culture and tissue repair

Abstract Experiments and concepts related to the role of fibrin formation and fibrin resolution in tissue growth and tissue repair are reviewed. In tissue repair, fibrin is the scaffold for migrating cells and the fabric in which reparative connective tissue is laid down. During fibroblastic proliferation and capillary growth the fibrin is removed. In tissue culture, a simplified model of tissue repair, fibrinolysis liquefies the solid fibrin medium, thus impairing cellular propagation. Growth can be restored by addition of inhibitors of fibrinolysis. Pure strains of fibroblasts are fibrinolytically inactive. Kidney cells cultured in fluid suspension produce a fibrinolytic supernate. Histochemically assayed fibrinolytic activity is related primarily to vascular endothelial cells. Certain epithelial cells (cornea, vagina) also show fibrinolytic activity caused by an activator of plasminogen. In tissue repair and during embryogenesis, fibrinolytic activity is related to the presence of nutritive vascular structures.

A Comparative Study of Coagulation and Fibrinolysis in Blood from Normal Men and Women

It is well known that several coagulation factors increase in concentration in the blood during pregnancy (Pechet and Alexander, 1961; Kasper, Hogg, Aggeler and Stone, 1964), and changes in the fibrinolytic system have also been described (Brakman and Astrup, 1963). Some coagulation factors and components of the fibrinolytic system are reported to be influenced by male and female hormones (Tagnon, Schulman, Whitmore and Leons, 1953). Mixtures of progestational and oestrogenic hormones influence coagulation and fibrinolysis in blood (Brakman and Astrup, 1964a; Hougie, Rutherford, Banks and Coburn, 1965). An increase in fibrinolytic activity of the circulating blood during menstruation has been reported by some authors, though others have been unable to confirm this. It is often difficult to evaluate these results because inaccurate or insensitive assay methods have been used. The present paper attempts to establish carefully assayed, normal values of certain parameters of blood coagulation and fibrinolysis in peripheral blood from men and women in order to compare them and to elucidate their possible fluctuations during menstruation. Such data are needed for establishing the normal patterns of coagulation and fibrinolysis, and in order to evaluate the possible influence of male and female hormones on these patterns. The present report provides a baseline for further studies of coagulation and fibrinolysis in blood.

Thromboplastic and Fibrinolytic Activities in Vessels of Animals

Thromboplastic activity and concentration of plasminogen activator were assayed in the coats of arteries and veins from a number of species. The widely differing patterns found in these species suggest great variation in the tendency to deposit fibrin on the interior surface of the vessels. Several modes of regulating fibrin deposition after intimal injury exist in the animal organism. These observations may assist the evaluation of data obtained in experiments on animals, and they demonstrate certain limitations with respect to conclusions on pathology in man.