Download PDF
Thromb Haemost 1976; 36(01): 014-026
DOI: 10.1055/s-0038-1648005
Original Article
Schattauer GmbH

Molecular Size Distribution of Fibrinogen Derivatives Formed in Vitro and in Vivo: a Chromatographic Study

M. B Donati   *
1   Laboratory of Blood Coagulation, Medical Research Department, University of Leuven, Belgium
,
R Verhaeghe
1   Laboratory of Blood Coagulation, Medical Research Department, University of Leuven, Belgium
,
D. E Culasso   **
1   Laboratory of Blood Coagulation, Medical Research Department, University of Leuven, Belgium
,
J Vermylen
1   Laboratory of Blood Coagulation, Medical Research Department, University of Leuven, Belgium
› Author Affiliations
Further Information

Publication History

Received 25 September 1975

Accepted 02 April 1976

Publication Date:
03 July 2018 (online)

    Permissions and Reprints

Summary

Using gel chromatography, fibrinogen derivatives present in purified systems or in biological fluids were separated and partially characterized. Eight groups of fibrinogen derivatives could be separated by gel filtration through 6% agarose in large columns, four with an elution volume smaller and four groups with an elution volume larger than that of fibrinogen. Careful calibration of the column allowed estimation of the diffusion coefficients of some of the derivatives and, thus, comparison with derivatives previously identified. Three, rather than two, groups of intermediate derivatives were observed during the degradation of human fibrinogen by plasmin in vitro or in vivo. One of these had a marked tendency to polymerize.

A rather distinct difference in elution pattern was found between plasma obtained during streptokinase administration and from patients with intravascular coagulation.

* Present address: Laboratory for Haemostasis and Thrombosis Research, ‘Mario Negri’ Institute, Via Eritrea, 62 – 20157 Milano, Italy.


** Present address: Avellaneda 2127, Cordoba, Argentina.


 

  • References

  • 1 Alkjaersig N, Fletcher A. P, Sherry S. 1962; Pathogenesis of the coagulation defect developing in pathological plasma proteolytic (“fibrinolytic”) states. II. The significance, mechanism and consequences of defective fibrin polymerization. Journal of Clinical Investigation 41: 917.
    CrossrefPubMedGoogle Scholar
  • 2 Alkjaersig N, Vermylen J, Fletcher A. P. 1969; Fibrinogen proteolysis in vitro by plasmin. Federation Proceedings 28: 640.
    PubMedGoogle Scholar
  • 3 Allison A. C, Humphrey J. H. 1960; A theoretical and experimental analysis of double diffusion precipitate reactions in gels, and its application to characterization of antigens. Immunology 3: 95.
    PubMedGoogle Scholar
  • 4 Andrews P. 1965; The gel-filtration behaviour of proteins related to their molecular weights over a wide range. Biochemical Journal 96: 595.
    CrossrefPubMedGoogle Scholar
  • 5 Blättler W, Straub P. W, Peyer A. 1974; Effect of in vivo produced fibrinogen-fibrin intermediates on viscosity of human blood. Thrombosis Research 4: 787.
    CrossrefPubMedGoogle Scholar
  • 6 Blombäck B, Blombäck M, Finkbeiner W, Holmgren A, Kowalska-Loth B, Olovson G. 1974; Enzymatic reduction of disulfide bonds in fibrinogen by the thioredoxin system. I. Identification of reduced bonds and studies of reoxidation process. Thrombosis Research 4: 55.
    CrossrefPubMedGoogle Scholar
  • 7 Blombäck M. 1958; Purification of antihemophilic globulin. I. Stability of antihemophilic globulin activity in fraction I-O and a method for its partial separation from fibrinogen. Arkiv for Kemi 12: 387.
    PubMedGoogle Scholar
  • 8 Collen D, Tytgat G. N, Claeys H, Piessens R. 1972; Metabolism and distribution of fibrinogen. I. Fibrinogen turnover in physiological conditions in humans. British Journal of Haematology 22: 681.
    CrossrefPubMedGoogle Scholar
  • 9 de Gaetano G, Donati M. B, Vermylen J. 1971; Human platelet clumping by bovine fibrinogen during its degradation. Scandinavian Journal of Haematology, Supplement 13: 281.
    PubMedGoogle Scholar
  • 10 Donati M. B, Molla A, Vermylen J. 1971; The tanned red cell hemagglutination inhibition immunoassay and purified fibrinogen degradation products. Scandinavian Journal of Haematology Supplement 13: 91.
    PubMedGoogle Scholar
  • 11 Fisher S, Fletcher A. P, Alkjaersig N, Sherry S. 1967; Immunoelectrophoretic characterization of plasma fibrinogen derivatives in patients with pathological plasma proteolysis. Journal of Laboratory and Clinical Medicine 70: 903.
    PubMedGoogle Scholar
  • 12 Fletcher A. P. 1970; Fibrinogen proteolysis in vivo. Thrombosis et Diathesis Haemorrhagica, Supplement 39: 249.
    PubMedGoogle Scholar
  • 13 Fletcher A. P, Alkjaersig N. 1970; Blood hypercoagulability and thrombosis. Clinical Research 18: 531.
    PubMedGoogle Scholar
  • 14 Fletcher A. P, Alkjaersig N. 1973. Laboratory diagnosis of intravascular coagulation. In: Poller L. (ed.), Recent Advances in Thrombosis. Churchill Livingstone; Edinburgh: 87.
    Google Scholar
  • 15 Fletcher A. P, Alkjaersig N, Fisher S, Sherry S. 1966; The proteolysis of fibrinogen by plasmin: The identification of thrombin-clottable fibrinogen derivatives which polymerize abnormally. Journal of Laboratory and Clinical Medicine 68: 780.
    PubMedGoogle Scholar
  • 16 Gaffney P. J. 1973; The molecular and functional condition of plasma fibrinogen during thrombolytic therapy with streptokinase (SK). Thrombosis Research 2: 105.
    CrossrefPubMedGoogle Scholar
  • 17 Graeff H, von Hugo R. 1972; Identification of fibrinogen derivatives in plasma samples. Thrombosis et Diathesis Haemorrhagica 27: 610.
    PubMedGoogle Scholar
  • 18 Latallo Z. S, Teisseyre E. 1971; Practical method for separation of the active component from a mixture of early fibrinogen degradation products. Scandinavian Journal of Haematology, Supplement 13: 383.
    PubMedGoogle Scholar
  • 19 Lipinski B, Wegrzynowicz Z, Budzynsky A. Z, Kopec M, Latallo Z. S, Kowalski E. 1967; Soluble unclottable complexes formed in the presence of fibrinogen degradation products (FDP) during the fibrinogen-fibrin conversion and their potential significance in pathology. Thrombosis et Diathesis Haemorrhagica 17: 65.
    PubMedGoogle Scholar
  • 20 Mancini G, Carbonara O, Heremans J. F. 1965; Immuno chemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 2: 235.
    CrossrefPubMedGoogle Scholar
  • 21 Marder V. J, Shulman N. R. 1969; High molecular weight derivatives of human fibrinogen produced by plasmin. II. Mechanism of their anticoagulant activity. Journal of Biological Chemistry 244: 2120.
    PubMedGoogle Scholar
  • 22 Marder V. J, Shulman N. R, Carroll W. R. 1969; High molecular weight derivatives of human fibrinogen produced by plasmin. I. Physicochemical and immunological characterization. Journal of Biological Chemistry 244: 2111.
    PubMedGoogle Scholar
  • 23 Merskey C, Lalezari P, Johnson A. J. 1969; A rapid, simple, sensitive method for measuring fibrinolytic split products in human serum. Proceedings of the Society for Experimental Biology and Medicine 737: 871.
    PubMedGoogle Scholar
  • 24 Sasaki T, Page I. H, Shainoff J. R. 1966; Stable complex of fibrinogen and fibrin. Science (Washington) 152: 1069.
    CrossrefPubMedGoogle Scholar
  • 25 Shainoff J. R, Page I. H. 1962; Significance of cryoprofibrin in fibrinogen-fibrin conversion. Journal of Experimental Medicine 116: 687.
    CrossrefPubMedGoogle Scholar
  • 26 Smith G. F, Bang N. U. 1972; Formation of soluble fibrin polymers. Fibrinogen degradation fragments D and E fail to form soluble complexes with fibrin monomer. Biochemistry 11: 2958.
    CrossrefPubMedGoogle Scholar
  • 27 Stewart G. J, Niewarowski S. 1969; Nonezymatic polymerization of fibrinogen by protamine sulfate. An electron microscope study. Biochimica Biophysica Acta 194: 462.
    CrossrefPubMedGoogle Scholar
  • 28 Vermylen J, Donati M. B, Verstraete M. 1971; The identification of fibrinogen derivatives in plasma and serum by agarose gel filtration. Scandinavian Journal of Haematology, Supplement 13: 219.
    PubMedGoogle Scholar
  • 29 Verstraete M, Vermylen J, Donati M. B. 1971a The effect of streptokinase infusion on chronic arterial occlusions and stenoses. Annals of Internal Medicine 74: 377.
    PubMedGoogle Scholar
  • 30 Verstraete M, Vermylen J, Donati M. B. (eds.) 1971b Fibrinogen Degradation Products. Scandinavian Journal of Haematology. Supplement 73.
    PubMedGoogle Scholar
  • 31 von Hugo R, Graeff H. 1973; Fibrin-I degradation products with a molecular weight higher than that of fibrinogen. Identification and characterization of in vitro products from human plasma. Thrombosis et Diathesis Haemorrhagica 29: 122.
    PubMedGoogle Scholar