Fibrin-I Degradation Products with a Molecular Weight Higher than That of Fibrinogen

Summary

The observation of intravascular lysis of fibrin deposits and of fibrinogen derivatives with a molecular weight higher than the parent molecule in human cases of disseminated intravascular coagulation (DIC) initiated the following in vitro study. Following streptokinase induced plasma clot solubilization fibrinogen derivatives were investigated after ß-alanine precipitation of the plasma samples by polyacrylamide (PAA) gel electrophoresis, intra gel immunoprecipitation, two dimensional gel electrophoresis and by agarose gel filtration. Three fibrin-i degradation products were observed and characterized according to their relative electrophoretic mobility in 5% PAA gel: 0.23, 0.35, 0.46 (fibrinogen: 0.43) x 10^-5 cm²/V x sec. They could also be demonstrated after electrophoresis in the presence of 5 M urea. Agarose gel filtration yielded one peak at 180 ml of effluent volume. The 0.23 derivative was eluted in the peak fractions, whilst the 0.35 and 0.46 derivatives were eluted together at approximately 201 ml of the effluent volume (fibrinogen: 225 ml). This indicates, that the three fibrin-i degradation products described are molecular entities with molecular weights higher than fibrinogen and, that the 0.46 derivative has an increased charge/molecular size ratio in comparison with fibrinogen. Corresponding data were obtained by two dimensional gel electrophoresis in gels of different pore size.

• References

• 1 Beller F.K, Graeff H. 1970. Equipment and general requirement of the coagulation laboratory. In: Bang N, Beller F. K, Deutsch E , Mammen E. (eds.) Methods and Theories of Blood Cocigidation. Academic Press; New York, G. Thieme, Stuttgart: 57.
• 2 Fletcher A.P, Alkjaersig N, O’Brien J. 1970. Blood hypercoagulability and thrombosis. In Abstract volume, XIII. International Congress of Hematology. Munich, 2-8 August, 1970, 244.
• 3 Gaffney P.J. 1971; Molecular aspects of fibrin clot solubilization. Nature New Biology 234: 281.
• 4 Graeff H, Kuhn W, Bleyl U. 1967; Verbrauchskoagulopathie und Lysekoagulopathie bei menschlichen Äquivalenten des Sanarelli-Shwartzman-Phänomens (generalisiertes Shwartz - man-Phänomen). Thrombosis et Diathesis Haemorrhagica 17: 144.
• 5 Graeff H, Wreschniok K, von Hugo R. 1971. Identification of fibrin and/or fibrinogen degradation products in plasma samples by PAA gel electrophoresis and intra gel immunoprécipitation. In: Abstract volume, II. International Congress on Thrombosis and Haemostasis. Oslo; 12-16 July, 1971, 150.
• 6 Graeff H, von Hugo R. 1972; Identification of fibrinogen derivatives in plasma samples. Thrombosis et Diathesis Haemorrhagica 27: 610.
• 7 Graeff H, von Hugo R, Kuhn W, Scholz H, Ernst A. 1973 Fibrinogen derivatives with a molecular weight higher than the parent molecule in cord vein plasma of newborns. Klinische Wochenschrift. (in press)
• 8 Kuhn W, Graeff H. 1970. Gerinnungsstörungen in der Geburtshilfe. G. Thieme; Stuttgart.:
• 9 Mancini G, Vaerman J.P, Carbonara A.O, Heremans J.F. 1964. A single-radial- diffusion method for the immunological quantitation of proteins. In: Peeters H. (ed.) Proceedings of the Xlth Colloquium on Protides of the Biological Fluids. Elsevier; Amsterdam 370.
• 10 Maurer H.R. 1968. Disk-Elektrophorese. Walter de Gruyter & Co; Berlin.:
• 11 Niewiarowski S. T, Nandi M. 1971; Acrylamide gel electrophoresis of fibrinogen and fibrin degradation products. British Journal of Haematology 21: 71.
• 12 Raymond S. 1968. Acrylamide gel electrophoresis. In: Williams C. A, Chase M.W. (eds.) Methods in Immunology and Immunochemistry. Academic Press; New York: 47.
• 13 Vermylen J, Donati M.B, Verstraete M. 1971. The identification of fibrinogen derivatives in plasma and serum by agarose gel filtration. In: Verstraete M, Vermylen J , Donati M. B. (eds.) Fibrinogen Degradation Products. Scandinavian Journal of Haematology, Supplementum. vol. 13 219.