Sten Müllertz

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.).

An Activator System in Blood Indispensable for Formation of Plasmin by Streptokinase.

Summary 1. Streptokinase transforms a proactivator in blood to an activator, which converts plasminogen to plasmin. Streptokinase does not react directly with plasminogen. 2. A low content of plasminogen pro-activator in bovine blood is the reason for the incomplete activation of preparations of bovine plasminogen by streptokinase. In human globulin a large excess of plasminogen activator is formed by streptokinase. 3. The large activities usually observed by the activation of human globulin with streptokinase is caused by the action of this activator on the plasminogen contained in the fibrin substrate.

A plasminogen activator in spontaneously active human blood.

Summary1. Fibrinolytically active blood, as obtained from the living and dead human organism, contains a plasminogen activator. The amount of this activator exceeds many times that needed for the complete activation of the plasminogen present in human blood. 2. The plasminogen activator in blood differs from the tissue activator, fibrinokinase, and is probably formed from a precursor contained in the blood.Summary 1. Fibrinolytically active blood, as obtained from the living and dead human organism, contains a plasminogen activator. The amount of this activator exceeds many times that needed for the complete activation of the plasminogen present in human blood. 2. The plasminogen activator in blood differs from the tissue activator, fibrinokinase, and is probably formed from a precursor contained in the blood.

ACTIVATION OF PLASMINOGEN

Plasmin is the proteolytic and fibrinolytic enzyme of blood. It is normally present in blood as an inactive precursor, plasminogen. Activation of plasminogen to plasmin may occur in the animal organism under various conditions. After death strong fibrinolytic activity is often found in human blood. In vitro, a conversion of plasminogen into plasmin can be effected by dilution or precipitation procedures or by treating serum, plasma, or globulin fractions with chloroform and related substances, with tissue or tissue extracts, or with trypsin. Culture filtrates from certain streptococci and staphylococci contain streptokinase and staphylokinase, substances that effect the activation of plasminogen. Before 1952, among several discrepancies noted in the behavior of these enzymes, the most obvious were: the difference in reaction of animal and human plasminogen to the activators, streptokinase and tissue; and the varying reaction of fibrin substrates and other protein substrates to the active substances. Animal plasminogens were partially or totally resistant to streptokinase, while human plasminogen was activated quickly and completely. On the other hand, tissue activator produced activities of the same magnitude in all plasminogens, whatever substrates were used to determine the activity. When a bovine fibrin substrate was used, the lytic effect of human globulin activated by streptokinase was far greater than that of human or animal globulin activated by tissue activator. Any hypothesis of the mechanism of activation of plasminogen should supply a reasonable explanation of these discrepancies. Surveys of earlier and recent literature on these subjects are given by Macfarlane and Biggs (1948), Astrup (1956), and Mullertz (1956). During recent years, information concerning the mechanism of activation of plasminogen has been obtained primarily from studies on the effect of streptokinase, on the activator in spontaneously fibrinolytic human blood, and on the influence of fibrin and inhibitors on the activation process in blood.

Anticoagulant Therapy with Dicumarol Maintained during Major Surgery

Most postoperative thromboses are probably initiated before or during surgical interventions and most of the fatal embolisms occur during the early postoperative period. As a complete prophylaxis, Dicumarol therapy was begun before, and maintained at an effective level during and after, major surgical interventions in 11 patients with a marked thromboembolic predisposition. No excessive hemorrhage, thromboembolic incidents or other unusual complications were encountered. The precautions necessary for a safe performance of the procedure are described.

Effect of carboxylic and amino acids on fibrinolysis produced by plasmin, plasminogen activator and proteases.

Summary 1. Fibrinolysis produced by activation of plasminogen in bovine fibrin by plasminogen activator preparations from human blood was increased considerably by di-and tri-carboxylic acids and decreased by diaminomonocarboxylic acids. 2. Fibrinolytic activity of a number of proteases was generally not significantly influenced. Bovine plasmin was moderately inhibited by lysine.Summary1. Fibrinolysis produced by activation of plasminogen in bovine fibrin by plasminogen activator preparations from human blood was increased considerably by di-and tri-carboxylic acids and decreased by diaminomonocarboxylic acids. 2. Fibrinolytic activity of a number of proteases was generally not significantly influenced. Bovine plasmin was moderately inhibited by lysine.