Fibrinolytic Activity of Thrombin Preparations

Summary

Some thrombin samples have a slight unspecific protease activity probably caused by contaminating plasmin. All investigated samples were fibrinolytically active. This activity was caused by an activator of plasminogen. Fibrinolytic activity was apparently produced by two components of the thrombin preparations. One of these components was a contaminant with fibrinolytic activity but with no thrombin activity. This component could be separated from the thrombin by simple chemical procedures. The other fibrinolytic component appeared to be the thrombin molecule per se. It was not fibrinolytically active when used in the low concentrations required for clotting of fibrinogen, but in high concentrations, assayed on the fibrin plate, it activated plasminogen. In the accurate assay of fibrinolytic agents it is necessary to use preparations of thrombin from which the contaminating fibrinolytic agent has been removed.

• References

• 1 Astrup T, Permin P. M. Fibrinokinas© and fibrinolytic enzymes. Nature 161: 689 1948;
• 2 Astrup T, Müllertz S. The fibrin plate method for estimating fibrinolytic activity. Arch. Biochem. 40: 346 1952;
• 3 Astrup T, Sterndorjf I. The effects of sodium citrate and an excess of plasminogen on fibrinolytic agents. Thrombos. Diathes. haemorrh. (Stuttg) 04: 462 1960;
• 4 Eichenberger E, Kickhöfen B, Schmidhauser-Kopp M, Schönholzer G. Über die fibrinolytische Wirkung von Thrombin. Schweiz. med. Wschr. 84: 65 1954;
• 5 Guest M. M, Ware A. G. Fibrinolytic activity of purified thrombin. Science 112: 21 1950;
• 6 Hink H. J, McDonald J. K. Preparation of profibrinolysin free fibrinogen and thrombin from human plasma. Nature 194: 1080 1962;
• 7 Hudemann S. Thrombinwirkung und Fibrinolyse in gereinigten Gerinnungs-Systemen. Kolloid-Z. 92: 189 1940;
• 8 Loki K, Gladner J. A, Folk J. E, Kominz D. R. The mode of action of thrombin. Thrombos. Diathes. haemorrh. (Stuttg) 02: 205 1958;
• 9 Landaburu R. H, Seegers W. H. The acétylation of thrombin. Canad. J. Biochem. 37: 1361 1959;
• 10 Landaburu R. H, Seegers W. H. The acetylation of prothrombin. Canad. J. Biochem. 38: 613 1960;
• 11 Lassen M. Heat dénaturation of plasminogen in the fibrin plate method. Acta physiol. scand. 27: 371 1962;
• 12 Markus G, Arnbrus G. M. Selective inactivation of the plasminogen contaminant in thrombin. Nature 188: 582 1960;
• 13 Nolf P. Contribution a l’etude de la coagulation. 5. La fibrinolyse. Arch. int. Physiol. 06: 306 1908;
• 14 Permin P. M. Undersogelser over fibrinolytiske enzymer. Thesis: University of Copenhagen; 1949
• 15 Quick A. J, Hussey G. V. Initiation of the clotting of blood. Proc. Soc. exp. Biol. 80: 40 1952;
• 16 Schultze H. E, Schwick G. Über den Mechanismus der Thrombinbildung im isolierten System. Z. physiol. Chem. 289: 26 1951;
• 17 Seegers W. H. Purification of prothrombin and thrombin. Chemical properties of purified preparations. J. biol. Chem. 136: 103 1940;
• 18 Seegers W. H. Coagulation of the blood. Harvey Lect. 47: 180 1952;
• 19 Seegers W. H, Landaburu R. H. Esterase and clotting activity derived from purified prothrombin. Amer. J. Physiol. 191: 167 1957;
• 20 Seegers W. H, Levine W. G, Shepard R. S. Further studies on the purification of thrombin. Canad. J. Biochem. 36: 603 1958;
• 21 Seegers W. H, Shepard R. S, Landaburu R. H. Ultracentrifugation of acetylated thrombin. Thrombos. Diathes. haemorrh. (Stuttg) 04: 299 1960;
• 22 Siegel M, Cliffton E. E. Role of a contaminant in thrombin in human fibrinolysis assay system. J. gen. Physiol. 40: 377 1957;
• 23 Stroyer-Rasmussen P. Purification of thrombin by chromatography. Biochem. biophys. Acta. 16: 157 1955;
• 24 Strässle R. Chromatographie von Thrombin. Biochem. Biophys. Acta. 73: 462 1963;
• 25 De Vreker R. A, Vermylen C, Verstraete M. Purification of thrombin for use as a fibrinolytically inert reagent. Protides Biol. Fluids, Proc. Colloq. 10: 343 1962;