Quantitation of the Coagulation Inhibition in Vivo Due to Breakdown Products of Fibrin

Summary

Degradation products of human fibrinogen were prepared by in vitro lysis of fibrin clots by urokinase activation and injected into rabbits on a quantitative basis. The dose necessary to anticoagulate the animal was equal to 2½ to 3 times the animals’ fibrinogen level. The effect on whole blood clotting time and thrombin time lasted for approximately 2 hrs. The “r” time of the TEG returned to normal after 1 hr while the “Max” value remained abnormal for more than 120 min. Degradation product E was shown to clear more rapidly than D by immunochemical techniques. The overall T ½ clearance was found to be approximately 12 hrs.

• References

• 1 Triantaphyllopoulos D. C. Effects of intravenous injections of the anti-coagulant fraction of incubated fibrinogen on blood coagulation. Canad. J. Biochem 38: 909 1960;
• 2 Lewis J. H, Wilson J. H. Fibrinogen breakdown products. Amer. J. Physiol 209: 1053 1965;
• 3 Better F. K, Moki M. Properties of fibrinogenolysis and fibrinolysis products in immune assays. Thrombos. Diathes. haemorrh. (Stuttg.) 18: 114 1967;
• 4 Rodriguez-Erdmann F. Über eine einfache Methode zur wiederholten Blutgewinnung beim Kaninchen. Pflügers Arch. ges. Physiol 269: 306 1959;
• 5 Astrup T, Glas P, Kok P. Assay of the plasminogen activator intissues. (In press, 1968).
• 6 Marchai G, Leroux M. E, Semama M. Atlas de Thrombodynamographie. Service de Propogande Edition. 1959
• 7 Godai H. C, Helle I. The influence of flbrinogenolytic and fibrinolytic split products on the last stage of coagulation. Scand. J. clin. Lab. Invest 15: 327 1963;
• 8 Schulz F. H. Eine einfache Bewertungsmethode von Leberparenchymschäden (volumetri-sche Fibrinbestimmung). Actahepat. (Hamburg) 3: 306 1955;
• 9 Ratnoff O. D, Menzi O. Estimation of fibrinogen in small samples of plasma. Blood Coagulation, Hemorrhage and Thrombosis. 224 Tocantins L. M, Kazal L. A. eds. Grune & Stratton; New York: 1964
• 10 McKay G. G. Practical application of Immunoelectrophoresis. Lab. Synopsis 2:1. Hoechst Pharmaceutical Co.; Kansas City, Mo.: 1967
• 11 Mancini G, Vaerman J. P, Carbonara A. O, Heremans J. F. Simple Radial Immunodiffusion. Lab. Synopsis 1: 43. Lloyd Bros. Inc.; Cincinnati, Ohio: 1965
• 12 Hill B. A. Principles of Medical Statistics. Oxford University Press; New York: 1961
• 13 Nussenzweig V, Seligmann M, Grabar P. Les Products De Degradation Du Fibrinogene Humain Par La Plasmine. Ann. Inst. Pasteur 100: 377 1961;
• 14 Larrieu M. J, Marder V. J, Onceman S. Effects of fibrinogen degradation products on platelets and coagulation. Diffuse intravascular clotting. Trans, of the conf. of the Internat. Comm. on Hemostasis and Thrombosis. F. K. Schattauer; Stuttgart: 1966
• 15 Fletcher A. P, Alkjaersig N, Fisher S, Sherry S. The proteolysis of fibrinogen by plasmin. The identification of thrombin clottable fibrinogen derivatives which polymerize abnormally. J. Lab. clin. Med 68 (03) 780 1966;
• 16 Niewiarowski S, Kowalski E. Un Nouvel anticoagulant derive die fibrinogène. Rev. Hémat 13: 320 1958;
• 17 Triantaphyllopoidos D. C. Anticoagulant effect of incubated fibrinogen. Canad. J. Biochem 36: 248 1958;
• 18 Bang N. U. Normal and abnormal fibrin polymerization. Thrombos. Diathes. haemorrh. (Stuttg.) Suppl 13: 131 1963;
• 19 Wilson P. A, McNicol G. P, Douglas A. S. Effect of Fibrinogen degradation products on platelet aggregation. J. clin. Pathol 21: 147 1968;
• 20 Fletcher A. P, Alkjaersig N, Sherry S. Pathogenesis of the coagulation defect developing during pathological plasma proteolytic (fibrinolytic) states. The significance of fibrinogen proteolysis and circulating fibrinogen breakdown products. J. clin. Invest 41: 896 1962;
• 21 Steichele D. F, Herrscheein H. J. Immunochemischer Nachweis von Fibrinogenderivaten im Urin bei Verbrauchskoagulopathien. Thrombos. Diathes. haemorrh. (Stuttg.) 19: 248 1968;