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Thromb Haemost 1967; 18(03/04): 487-498
DOI: 10.1055/s-0038-1655058
Originalarbeiten — Original Articles — Travaux Originaux
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Separation and Estimation of Split “Products” of Fibrinogen and Fibrin in Human Serum

J. E Niléhn
1   From the Department of Clinical Chemistry (Head: C.-B. Laurell, M. D.) and the Coagulation Laboratory (Head: I. M. Nilsson, M. D.), University of Lund, Allmänna Sjukhuset, Malmö, Sweden
› Author AffiliationsThis investigations was supported by grants from the Medical Faculty, University of Lund and from the Fylgia Foundation.
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Publication Date:
26 June 2018 (online)

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Summary

Pure fibrinogen and fibrinogen in plasma respectively, were digested with plasmin under various conditions. The split products obtained were afterwards separated on Sephadex G 200 and determined immunologically. The investigation showed that when plasmin digested plasma is separated by gel filtration high molecular weight split products with antigenic determinants for both D and E products occur in at least 3 different main types, which are eluted in the “19 S” and “7 S” peaks. On digestion of pure fibrinogen investigated in the same way only 2 main types of split products occurs in the same region. In the “4 S” peak D and E products occur as end degradation products.

The amount of split products formed in serum samples with fibrinolysis is larger than in those with fibrinogenolysis.

Split products in sera from patients with different diseases were identified after gel filtration on Sephadex G 200. As a rule, they were eluted together with the macro - globulins (“19 S”) but samples from patients with advanced fibrinolytic conditions were also found to have split products of lower molecular weight, which were eluted later in the “7 S” and “4 S” peaks.

With the immunologic technique used split products in the serum can be determined down to a concentration of 0.5 mg/100 ml. Split products were found in a concentration between 1 and 45 mg/100 ml in certain patients with liver disease, blood disease, cancer and thrombosis, but not in any of the healthy subjects studied.

 

  • References

  • 1 Alkjaersig N, Fletcher A. P, Sherry S. The mechanism of clot dissolution by plasmin. J. clin. Invest. 38: 1086 1959;
    CrossrefPubMedSearch in Google Scholar
  • 2 Alkjaersig N, Fletcher A. P, Sherry S. Pathogenesis of the coagulation defect developing during pathological plasma proteolytic (“fibrinolytic”) states. II. The significance, mechanism and consequences of defective fibrin polymerization. J. clin. Invest. 41: 917 1962;
    CrossrefPubMedSearch in Google Scholar
  • 3 Alkjaersig N, Fischer S. h. Proteolysis of fibrinogen by plasmin. Thrombos. Diathes. haemorrh. (Stuttg) 11: 284 1964;
    PubMedSearch in Google Scholar
  • 4 Ambrus G, Back N, Ambrus J. On the mechanism of thrombolysis by plasmin. Circulat. Res. 10: 161 1962;
    CrossrefPubMedSearch in Google Scholar
  • 5 Blombäck B, Blombäck M. Purification of human and bovine fibrinogen. Arkiv for kemi. 10: 415 1956;
    PubMedSearch in Google Scholar
  • 6 Fletcher A. P, Alkjaersig N, Fischer S. h, Sherry S. The proteolysis of fibrinogen by plasmin : The identification of thrombin-clottable fibrinogen derivatives which polymerize abnormally. J. Lab. clin. Med. 68: 780 1966;
    PubMedSearch in Google Scholar
  • 7 Fox Jr. F. J, Wide L, Killander J, Gemzell G. Determination of fibrinogen and fibrinolysis products in human plasma by an immunochemical method. Scand. J. clin. Lab. Invest 17: 341 1965;
    CrossrefPubMedSearch in Google Scholar
  • 8 Ganrot P. O. On the determination of molar concentration of plasmin and plasmin inhibitors. Acta chem. scand.. (In press 1967.)
    PubMed
  • 9 Hedner U, Nilsson I. M. Determination of plasminogen in human plasma by a casein method. Thrombos. Diathes. haemorrh. (Stuttg) 14: 545 1965;
    PubMedSearch in Google Scholar
  • 10 Hemker H. C, Fekkes N, Hensen A, Schrijver H, Loeliger E. A. Quantitation of circulating fibrinogen breakdown products in intravascular clotting. Thrombos. Diathes. haemorrh. (Stuttg.) Suppl. 20 227 1966;
    PubMedSearch in Google Scholar
  • 11 Laurell G-B. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. An. Biochem. 15: 45 1966;
    CrossrefPubMedSearch in Google Scholar
  • 12 Merskey G. L, Kleiner G. J, Johnson A. J. Quantitative estimation of split products of fibrinogen in human serum, relation to diagnosis and treatment. Blood 28: 1 1966;
    PubMedSearch in Google Scholar
  • 13 Miller L, Houghton J. A. The micro-Kjeldahl determination of the nitrogen content of amino acids and proteins. J. biol. Chem. 159: 373 1945;
    PubMedSearch in Google Scholar
  • 14 Mirsky I. A. Inhibition of ß-hemolytic streptococci fibrinolysin by trypsin inhibitor (antiprotease). Science 100: 198 1944;
    CrossrefPubMedSearch in Google Scholar
  • 15 Niléhn J-E, Nilsson I. M. Demonstration of fibrinolytic split products in human serum by an immunological method in spontaneous and induced fibrinolytic states. Scand. J. Haemat. 02: 313 1964;
    PubMedSearch in Google Scholar
  • 16 Niléhn J-E, Robertson B. On the degradation products of fibrinogen or fibrin after infusion of streptokinase in patients with venous thrombosis. Scand. J. Haemat. 02: 267 1965;
    PubMedSearch in Google Scholar
  • 17 Niléhn J-E. Split products of fibrinogen after prolonged interaction with plasmin. Thrombos. Diathes. haemorrh. (Stuttg.). (In press 1967.)
    PubMed
  • 18 Nilsson I. M, Blombäck M, Francken I. v. On an inherited autosomal hemorrhagic diathesis with antihemophilic globulin (AHG) deficiency and prolonged bleeding time. Acta med. scand. 159: 35 1957;
    PubMedSearch in Google Scholar
  • 19 Norman P. S, Hill B. M. Studies of the plasmin system. III. Physical properties of the two plasmin inhibitors in plasma. J. exp. Med 108: 39 1958;
    PubMedSearch in Google Scholar
  • 20 Nussenzweig V, Seligmann M, Pelmont J, Grabar P. Les produits de dégradation du fibrinogène humain par la plasmine. I. Separation et propriétés physico-chimiques. Ann. Inst. Pasteur 100: 377 1961;
    PubMedSearch in Google Scholar
  • 21 Schnitze H. E, Heimburger N, Heide K, Haupt H, Störiko K, Schwick H. G. Preparation and characterization of α1-trypsin inhibitor and α2-plasmin inhibitor of human serum. Proc. 9th Congr. europ. Soc. Hemat. Lisbon. 1963: 1315-1320 Karger; Basel/New York.:
    Search in Google Scholar