Fibrinogen and its Derivatives: Cofactors in the Intrinsic Generation of Thrombin

D.C Triantaphyllopoulos; L.T Ryan

doi:10.1055/s-0038-1647923

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1976; 35(02): 305-313
DOI: 10.1055/s-0038-1647923

Original Article

Schattauer GmbH

Fibrinogen and its Derivatives: Cofactors in the Intrinsic Generation of Thrombin

D.C Triantaphyllopoulos

¹American National Red Cross, Blood Research Laboratory, Bethesda, Maryland 20014 and Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, D. C. 20007

,

L.T Ryan

¹American National Red Cross, Blood Research Laboratory, Bethesda, Maryland 20014 and Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, D. C. 20007

› Author Affiliations

Abstract

Summary

The simultaneous addition of suboptimal concentrations of factor VIII and intact or plas-min-lysed fibrinogen into mixtures of the vitamin K dependent factors, phospholipids, adsorbed bovine serum (supplier of factor V) and calcium, increased the amount of thrombin which was generated three to twenty times over the sum of the amounts which were generated when factor VIII, or fibrinogen, or its derivatives were added separately into the thrombin generating mixture. When factor VIII was added together with both fibrinogen and its derivatives, the amount of thrombin generated was even greater, about 130% larger than the amount which was generated in the presence of equal concentrations of only intact fibrinogen plus factor VIII. Addition of albumin instead of fibrinogen or its derivatives has a similar but significantly lower effect on thrombin generation. It appears, therefore, that both intact fibrinogen and its plasminolytic derivatives, singly or in combination, and to a lesser extent albumin, act as cofactors in the reaction which is regulated by factor VIII.

Full Text

References

References
1 Aronson D. L, Mustafa A. J, Mushinski J. F. 1969; Purification of human factor X and comparison of peptide maps of human factor X and prothrombin. Biochimica Biophysica Acta 188: 25.
2 Barrow E. S, Lester R. H, Johnson A. M, Graham J. B. 1972; Production of antihemophilic factor (factor VJII) from albumin. American Journal of Physiology 222: 920.
3 Biggs R. (ed.) 1972. Human Blood Coagulation, Haemostasis and Thrombosis. Blackwell Scientific Publications; Oxford: 609.
4 Biggs R, MacFarlane R. G, Denson K. W. E, Ash B. T. 1965; Thrombin and the interaction of factors VIII and IX. British Journal of Haematology 11: 276.
5 Chandra S, 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 Chandra S, Triantaphyllopoulos D. C. 1973; Potentiation of the antifactor VIII effect of thrombin in plasma by the plasminolytic derivatives of fibrinogen and fibrin. Thrombosis et Diathesis Haemorrhagica 30: 235.
7 Cuatrecasas P, Wilchek M, Anfinsen C. B. Selective enzyme purification by affinity chromatography. Proceedings of the National Academy of Sciences 61. 636.
8 Goldstein R, Zonderman E. B. 1958 Purification of Drothrombin and its separation from other coagulation factors. Proceedings of the International Congress, International Society of Haematology, Rome,. II Pensiero Scientifico, p. 1006.
9 Kirby E. P, Martin N, Marder V. J. 1974; Degradation of bovine factor VIII by plasmin and trypsin. Blood 43: 629.
10 Klein P. D, Seegers W. H. 1950; The nature of plasma antithrombin activity. Blood 5: 742.
11 Mysliwiec M, Arnesen H, Godal H. C. 1973; The effect of fibrinogen degradation products on plasmin activity. Thrombosis et Diathesis Haemorrhagicia 29: 592.
12 Newman J, Johnson A. J, Karpatkxn M. H, Puszkin S. 1971; Methods for the production of clinically effective intermediate and high purity factor VIII concentrates. British Journal of Haematology 21: 1.
13 Osterud B, Rapaport S. I, Scheffman S, Chong M. M. Y. 1971; Formation of intrinsic factor X-activator activity with special reference to the role of thrombin. British Journal of Haematology 643: 1971.
14 Penick G. D. 1957; Some factors that influence utilization of antihemophilic activity during clotting. Proceedings of the Society of Experimental Biology and Medicine 96: 211.
15 Seegers W. H. 1962. Prothrombin. Harvard University Press; Cambridge, Mass: 94.
16 Seegers W. H, Landaburu R. H, Fenichel R. L. 1957; Isolation of platelet cofactor I from plasma and some properties of the preparation. American Journal of Physiology 190: 1.
17 Sgouris J. T, Inman J. K, McCall K. B, Hyndman L. A, Anderson H. D. 1960; The preparation of human fibrinolysin (plasmin). Vox Sanguinis 5: 1960.
18 Sgouris J. T, Wickerhauser MD. 1973; Use of frozen cryoprecipitate for the preparation of clinical factor VIII concentrate. Transfusion 13: 399.
19 Siegelman A. M, Carlson A. S, Robertson T. 1962; Investigation of serum trypsin and related substances. I. The quantitative demonstration of trypsin-like activity in human blood serum by a micro-method. Archives of Biochemistry 97: 159.
20 Triantaphyllopoulos D. C. 1958; Anticoagulant effect of incubated fibrinogen. Canadian Journal of Biochemistry and Physiology 36: 249.
21 Triantaphyllopoulos D. C, Brunetti A. D, Triantaphyllopoulos E. 1970; Increased prothrombin conversion: A new activity of lysed fibrinogen. British Journal of Haematology 18: 127.
22 Triantyphyllopoulos E, Triantaphyllopoulos D. C. 1965; Variability of the anticoagulant fraction of incubated fibrinogen. American Journal of Physiology 208: 521.
23 Triantaphyllopoulos E, Triantaphyllopoulos D. C. 1967; New anticoagulant from lysed fibrinogen. British Journal of Haematology 13: 28.
24 Triantaphyllopoulos E, Triantaphyllopoulos D. C. 1973; Selected topics in blood coagulation. C. R. C. Critical Reviews in Biochemistry 1: 305.
25 Ware A. G, Seegers W. H. 1949; Two stage procedure for the quantitative determination of prothrombin concentration. American Journal of Clinical Pathology 19: 471.