Potentiation of the Anti-factor VIII Effect of Thrombin in Plasma by the Plasminolytic Derivatives of Fibrinogen and Fibrin

Summary

The activity of factor VIII in mixtures of native plasma or blood with fibrinogen derivatives at concentrations high enough to inhibit prothrombin consumption, is greatly reduced. On the other hand the activity of factor VIII was found normal in similar mixtures of adsorbed native plasma with fibrinogen derivatives, where no generation of thrombin could have taken place. The fibrinogen derivatives increased significantly the inactivating effect of low concentrations of thrombin on the activity of factor VIII of mixtures of adsorbed oxalated plasma with the derivatives. The same inactivating effect was exerted by fibrinogen derivatives heated at 60° C for 15 minutes and by plasmin lysed fibrin. In contradistinction addition of intact fibrinogen or fibrinogen derivatives to heat-defibrinated plasma protected factor VIII from inactivation by thrombin. When both, intact fibrinogen and its derivatives, were added simultaneously at the same concentrations at which they were added singly, the protective effect was intermediate between that exerted by intact fibrinogen and fibrinogen derivatives alone. Under these conditions the fibrinogen derivatives appeared as if they potentiated the inactivating effect of thrombin. Probably by inhibiting the formation of structural fibrin they increased the amount of thrombin, which remained unadsorbed and free to inactivate factor VIII.

^* Present address: Department of Hematology St. Vincent Hospital, Worcester, Mass. 01610. Reprint requests to Dr. Triantaphyllopoulos.

• References

• 1 Aronson D. L, Mustafa A. J, and Mushinski J. F. 1969; Purification of human factor X and comparison of peptide maps of human factor X and prothrombin. Biochimica et Bio-physica Acta 188: 25.
• 2 Biggs R, Macfarlane R. G, Denson K. W. E, and Ash B. T. 1965; Thrombin and the interaction of factors VIII and IX. British Journal of Haematology 11: 276.
• 3 Blombäck B. 1958; Studies on the action of thrombio enzymes on bovine fibrinogen as measured by N-terminal analysis. Arkiv för Kemi 12: 321.
• 4 Blombäck B, Blombäck M, and Nilsson I. M. 1957; Coagulation studies on reptilase and extract of the venom from Bothrops Jararaca. Thrombosis et Diathesis Haemorrhagica 1: 76.
• 5 Chandra S, and Triantaphyllopoulos D. C. 1972; Preparation of degradation products of fibrinogen free of plasmin and their effect on thrombin activity. Canadian Journal of Physiology and Pharmacology 50: 655.
• 6 Cuatrecasas P, Wilchek M, and Ankensen C. B. 1968; Selective enzyme purification by affinity chromatography. Proceedings of the National Academy of Sciences U.S.A 61: 636.
• 7 Goldstein R, and Zonderman E. B. 1960 Purification of prothrombin and its separation from other coagulation factors. Proceedings of the International Congress, International Society of Haematology, Rome (1958). Il Pensiero Scientifico, Rome, p. 1006.
• 8 Klein P. D, and Seegers W. H. 1950; The nature of plasma antithrombin activity. Blood 5: 742.
• 9 Kwaan H. C, and Barlow G. H. 1971; The mechanism of action of Arvin and Reptilase. Thrombosis et Diathesis Haemorrhagica, Suppl 47: 361.
• 10 Marciniak E, and Seegers W. H. 1962; Autoprothrombin C: A second enzyme from prothrombin. Canadian Journal of Biochemistry and Physiology 40: 597.
• 11 Norman J. C, Covelii V. H, and Sise H. S. 1960; Transplantation of the spleen. Experimental cure of hemophilia. Surgery 64: 1.
• 12 Penick G. D. 1957; Some factors that influence utilization of antihemophilic activity during clotting. Proceedings of the Society for Experimental Biology and Medicine 96: 277.
• 13 Seegers W. H, McClaughry R. I, and Fahey J. L. 1950; Some properties of purified prothrombin and its activation with sodium citrate. Blood 5: 421.
• 14 Triantaphyllopoulos D. C. 1958; Anticoagulant effect of incubated fibrinogen. Canadian Journal of Biochemistry and Physiology 36: 249.
• 15 Triantaphyllopoulos D. C, Chen C, and Triantaphyllopoulos E. 1969; Nature of the inhibition of prothrombin consumption by lysed fibrinogen. British Journal of Haematology 16: 589.
• 16 Triantaphyllopoulos D. C, and Popper M. R. 1972; Factor XIII consumption. Federation Proceedings (Abstracts) 31: 217.
• 17 Triantaphyllopoulos D. C, Triantaphyllopoulos E, and Chandra S. 1971; Effect of fibrinogen degradation produots on coagulation. Thrombosis et Diathesis Haemorrhagica Supph 47: 121.
• 18 Triantaphyllopoulos E, and Triantaphyllopoulos D. C. 1962; Coagulation studies on the electrophoretic fractions of AFIF. American Journal of Physiology 203: 595.
• 19 Triantaphyllopoulos E, and Triantaphyllopoulos D. C. 1965; a Variability of the anticoagulant fraction of incubated fibrinogen. American Journal of Physiology 208: 521.
• 20 Triantaphyllopoulos E, and Triantaphyllopoulos D. C. 1965; b Thermostable anticoagulant from the anticoagulant fraction of incubated fibrinogen. British Journal of Haematology 11: 331.
• 21 Triantaphyllopoulos E, and Triantaphyllopoulos D. C. 1967; New anticoagulant from lysed fibrinogen. British Journal of Haematology 13: 28.