Soluble Fibrin Complexes and Fibrinogen Heterogeneity in Diabetes mellitus

Summary

The presence of soluble fibrin complexes (SFC) measured by gel filtration of plasma on 4% agarose columns, fibrinogen heterogeneity on 3.5% SDS-polyacrylamide gels and the concentrations of several plasma proteins were evaluated in 39 patients with diabetes mellitus (DM) and 19 matched control subjects. A small but significant increase of SFC was found in DM (p<0.01). On individual basis 51.2% of the patients had increased SFC (>M + 2 SD of the controls). Polyacrylamide gel electrophoresis of the SFC showed no evidence of cross-linking or proteolysis. Plasma clots formed in the presence of EDTA and trasylol were analysed in SDS-polyacrylamide gels in a normal and two lower molecular weight fibrin bands (band I, II, III). The percentage of band I fibrinogen was in diabetics (65.3 ± 4.7%) lower than that of the controls (71.8 ± 4.5%) (p < 0.01). Fibrinogen levels, antithrombin III, α₁-antitrypsin, α₂-macroglobulin and plasminogen were significantly increased in DM. We suggest that in DM there is an enhancement of intravascular fibrin formation and accelerated fibrinogen degradation to lower molecular weight forms.

Key words

Diabetes mellitus - Soluble fibrin complexes - Fibrinogen heterogeneity

• References

• 1 Colwell JA, Halushka PV, Sarji K, Levine J, Sagel J, Nair RM G. Altered platelet function in diabetes mellitus. Diabetes 1976; 25 (suppl. 2): 826-831
• 2 Kwaan HC, Colwell JA, Cruz S, Suwanwela N, Dobbie JG. Increased platelet aggregation in diabetes mellitus. J Lab Clin Med 1972; 80: 236-246
• 3 Egeberg O. The blood coagulability in diabetic patients. Scand J Clin Lab Invest 1963; 15: 533-538
• 4 Mayne EE, Bridges JM, Weaver JA. Platelet adhesiveness, plasma fibrinogen and factor VIII levels in diabetes mellitus. Diabetologia 1970; 6: 436-440
• 5 Valdord-Hansen F. Coagulability in diabetics. Acta Med Scand 1967; suppl. 476: 147-157
• 6 Almér LO, Pandolfi M. Fibrinolysis and diabetic retinopathy. Diabetes 1976; 25 (suppl 2): 807-810
• 7 Ferguson JC, Mackay N, Philip JA D, Sumner DJ. Determination of platelet and fibrinogen half life with [75 Se] selenomethionin: studies in normal and in diabetic subjects. Clin Sci Mol Med 1975; 49: 115-120
• 8 O'Brien JR, Etherington MD, Jamienson S, Lawford P, Lincoln SV, Alkjaersig NJ. Blood changes in atherosclerosis and long after myocardial infraction and venous thrombosis. Thromb Diath Haemor 1975; 34: 483-497
• 9 Gurewich V, Lipinska I, Pulini M, Gordon E, Lipinski B. Fibrinogen, fibrinogen heterogeneity and fibrinolytic activity in diabetes mellitus. Thromb Haemost 1977; 38: 103
• 10 Ratnoff OD, Menzie C. A new method for the determination of fibrinogen in small samples of plasma. J Lab Clin Med 1951; 37: 316-320
• 11 Fletcher AP, Alkjaersig N, O'Brien J, Tulevski VG. Blood hyercoagulability and thrombosis. Trans Ass Amer Phys 1970; 83: 159-167
• 12 Mancini G, Carbonara CO, Heremans JF. Immunochemical quantitations of antigens by single radial immunodiffusion. Immunochemistry 1965; 2: 235-254
• 13 Hansen MS, Bang NU, Barton RD, Mattler LE. Enhancement of blood coagulation by soluble fibrin complexes. J Exper Med 1975; 141: 944-961
• 14 Stathakis NE, Mosesson MW, Chen AD, Galanakis DK. Cryoprecipitation of fibrin-fibrinogen complexes induced by the cold insoluble globulin of plasma. Blood 1978; 51: 1211-1222
• 15 Weber K, Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem 1969; 244: 4406-4412
• 16 Bang N, Chang M. Soluble fibrin complexes. Sem Thromb Hemostas 1974; 1: 91-109
• 17 Fletcher AP, Alkjaersig N. The use and monitoring of antithrombotic drug therapy. The need for a new approach. Thromb Haemostas 1977; 38: 881-892
• 18 Anaya-Galindo R, Shattil SJ, Shelburne JC, Coman RW. Soluble fibrin complexes in coronary disease. Thromb Res 1976; 9: 153-165
• 19 Carvalho AC, Lees RS, Vaillancourt RA, Cabral RB, Weinberg RM, Colmann RW. Intravascular coagulation in hyperlipidemia. Thromb Res 1976; 8: 843-857
• 20 Jones RL, Peterson CM. Reduced fibrinogen survival in diabetes mellitus; a reversible phenomenon. XVII Congress of the International Society of Hematology, Paris 1978 abstracts (I) 532
• 21 Ly B, Kierulf P, Jakobsen E. Stabilization of soluble fibrin/fibrinogen complexes by fibrin stabilizing Factor (FSF). Thromb Res 1974; 4: 509-522
• 22 Edgal W, Mckillop C, Howie PW, Forbes CD, Prendice CR M. Analysis of soluble fibrin complexes in patients with intravascular coagulation. Thromb Haemostas 1977; 38: 89
• 23 Graeff H, von HugoR, Hafter R. In vivo formation of soluble fibrin monomer complexes in human plasma. Thromb Res 1973; 3: 465-476
• 24 Mosesson MW, Alkjaersig N, Sweet B, Sherry S. Human fibrinogen of relatively high solubility. Comparative biophysical, biochemical and biological studies with fibrinogen of lower solubility. Biochemistry 1967; 6: 3279-3287
• 25 Galanakis DK, Mosesson MW, Stathakis NE. Human fibrinogen heterogeneities: Distribution and charge characteristics of chains of Aa origin. J Lab Clin Med 1978; 92: 376-386
• 26 Mosesson MW, Galanakis DK, Finlayson JS. Comparison of human plasma fibrinogen subtractions and early plasmic fibrinogen derivatives. J Biol Chem 1974; 249: 4656-4664
• 27 Lipinska I, Lipinski B, Gurewich V. Fibrinogen heterogeneity in human plasma. Electrophoretic demonstration of two major fibrinogen components. J Lab Clin Med 1974; 84: 509-516
• 28 Lipinska I, Lipinski B, Gurewich V, Hoffmann KD. Fibrinogen heterogeneity in cancer, in occlusive vascular disease and after surgical procedures. Amer J Clin Pathol 1976; 66: 958-966
• 29 Weinstein MJ, Deykin D. Quantitative abnormality of an Aa chain molecular weight form in the fibrinogen of cirrhotic patients. Brit J Haemat 1978; 40: 617-630