Degradation of Fibrinogen by Proteolytic Enzymes

S. P Miller; J Sanchez-Avalos

doi:10.1055/s-0038-1651245

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1968; 20(01/02): 015-030
DOI: 10.1055/s-0038-1651245

Originalarbeiten – Original Articles – Travaux Originaux

Schattauer GmbH

Degradation of Fibrinogen by Proteolytic Enzymes

II. Effect of the Products on Coagulation^[*]

Authors

S. P Miller M. D.¹

¹Division of Oncology, Maimonides Medical Center, and the Department of Medicine, State University of New York, Downstate Medical Center, Brooklyn, New York
J Sanchez-Avalos M. D.²

¹Division of Oncology, Maimonides Medical Center, and the Department of Medicine, State University of New York, Downstate Medical Center, Brooklyn, New York

Abstract

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Summary

Degradation products of fibrinogen and fibrin resulting from the hydrolytic action of plasmin, trypsin, chymotrypsin and papain were prepared and the two major polypeptide fragments were found to have inhibitory effects on the coagulation mechanism including inhibition of thromboplastin generation and inhibition of the conversion of the fibrinogen to fibrin. The inhibitory actions of each of the isolated components were characterized specifically for their role in each of these coagulation functions.

Both the slow (D) and fast (E) fragments of fibrinogen and fibrin hydrolysis by plasmin degradation showed equally inhibitory effects against fibrinogen to fibrin conversion by thrombin and fibrin monomer polymerization. The slow component of both was more inhibitory. Both fast and slow digestion products of tryptic hydrolysis inhibited thromboplastin generation and fibrinogen to fibrin conversion and fibrin monomer polymerization equally. The fast component of chymotrypsin hydrolysis showed greater inhibition against thromboplastin generation and fibrin monomer polymerization, than did the slow component. Only a slow moving (D) component was obtained with papain digestion. It had no inhibitory function against thromboplastin generation and only minimal effect against fibrin monomer polymerization. The mechanism of inhibition of the thromboplastin generation test by fibrinogen degradation products is a neutralization or inhibition of factor IX.

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References

References
1 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 1962; 41: 917-934
2 Bang N.U, Fletcher A.P, Alkjaersig N, Sherry S. Pathogenesis of the coagulation defect developing during pathological plasma proteolytic (fibrinolytic) states, III. Demonstration of abnormal clot structure by electron microscopy. J. clin. Invest 1962; 41: 935
3 Bamhardt M.I, Cress D.G, Henry R.L, Riddle J.M. Influence of fibrinogen split products on platelets. Thrombos. Diathes. haemorrh. (Stuttg.) 1967; 17: 78
4 Beck E.A, Jackson D.P. Studies on the degradation of human fibrinogen by plasmin and trypsin. Thrombos. Diathes. haemorrh. (Stuttg.) 1966; 16: 526
5 Biggs R, Douglas A.S. The thromboplastin generation test. J. clin. Path 1953; 6: 23
6 Blombäck B. Chemical aspects of fibrinogen and fibrin. In “fibrinogen and fibrin turnover of clotting factors”. Edit. -Hunter, Koller and Beck. Thrombos. Diathes. haemorrh. (Stuttg.) 1963; 13: 29 Suppl.
7 Donelly T.H, Laskowsky M, Notley N, Scheraga H.A. Equilibria in the fibrinogenfibrin conversion, II. Reversibility of the polymerization steps. Arch. Biochem 1955; 56: 369-387
8 Ferry J.D, Morrison P.R. Preparations and properties of serum and plasma proteins, VIII. The conversion of human fibrinogen to fibrin under various conditions. J. Amer. chem. Soc 1947; 69: 388
9 Fletcher A.P, Alkjaersig N. Plasma fibrinogen and hemostatic functions (Pathological and Genetic Disorders). In: Progress in Hematology. Editor-Brown and Moore; Grune and Stratton, New York: 1966: 246 Vol. V
10 Fletcher A.P, Alkjaersig N, Sherry S. Pathogenesis of the coagulation defect developing during pathological plasma proteolytic (fibrinolytic) states, I. The significance of fibrinogen proteolysis and circulating fibrinogen breakdown products. J. clin. Invest 1962; 41: 896
11 Gormsen J, Laursen B. Fibrinogen breakdown products and clotting parameters. Thrombos. Diathes. haemorrh. (Stuttg.) 1967; 17: 467
12 Jerushalmy Z, Zucker M.B. Some effects of fibrinogen degradation products (FDP) on blood platelets. Thrombos. Diathes. haemorrh. (Stuttg.) 1966; 15: 413-418
13 Kopec M, Budzyński A, Stachurska J, Wegrzynowicz Z, Kowalski E. Studies on the mechanism of interference by fibrinogen degradation products (FDP) with the platelet function. Role of fibrinogen in platelet atmosphere. Thrombos. Diathes. haemorrh. (Stuttg.) 1966; 15: 476-490
14 Kowalski E. Fibrinogen derived inhibitors in blood coagulation. Thrombos. Diathes. haemorrh. (Stuttg.) 1960; 4: 211-223 Suppl.
15 Kowalski E, Budzyński A.Z, Kopéc M. Studies on the molecular pathology and pathogenesis of bleeding in severe fibrinolytic states in dogs. Thrombos. Diathes. haemorrh. (Stuttg.) 1964; 12: 69-86
16 Kowalski E, Budzyński A.Z, Kopéc M. Circulating fibrinogen degradation products (FDP) in dog blood after intravenous thrombin infusion. Thrombos. Diathes. haemorrh. (Stuttg.) 1965; 13: 12-24
17 Kowalski E, Kopéc M, Wegrzynowicz Z. Influence of fibrinogen degradation products (FDP) on platelet aggregation, adhesiveness and viscous metamorphosis. Thrombos. Diathes. haemorrh 1963; 10: 406-423
18 Kunkel H.G. Zane electrophoresis. Meth. biochem. Anal 1954; 1: 141
19 Latałło Z.S, Budzyński A.Z, Lipinski B, Kowalski E. The inhibition of thrombin and of fibrin polymerization, two activities derived from plasmindigested fibrinogen. Nature (Lond.) 1964; 203: 1184-1185
20 Latałło Z.S, Fletcher A.P, Alkjaersig N, Sherry S. Inhibition of fibrin polymerization by fibrinogen proteolysis products. Amer. J. Phys 1962; 202: 681
21 Larrieu M.J, Marder V.J, Inceman S. The effects of fibrinogen degradation products on platelets and coagulation. Disseminated Intravascular Clotting. Thrombos. Diathes. haemorrh 1966; 20: 215-226 Suppl.
22 Lewis G.H, Wilson J.H. Fibrinogen breakdown products. Amer. J. Phys 1964; 207: 1053-1057
23 Lipinski B, Wegrzynowicz Z, Budzyński A.Z, Kopéc M, Latałło Z.S, Kowalski E. Soluble unclottable complexes formed in the presence of fibrinogen degradation products (FDP) during the fibrinogenfibrin conversion and their potential significance in pathology. Thrombos. Diathes. haemorrh 1967; 17: 65
24 Marder V.J, Larrieu M.J, Shulman N.R. Molecular characteristics and anticoagulant activity of intermediate products of fibrinogenolysis. (Abst.) Proc. Amer. Soc. Heamt; New Orleans La: 1966: 33
25 Nanninga L.B, Guest M.M. Preparation and properties of anticoagulant split products of fibrinogen and its determination in plasma. Thrombos. Diathes. haemorrh 1967; 17: 440
26 Niewiarowski S, Kowalski E. Un nouvel anticoagulant derive du fibrinogène. Rev. hémat 1958; 15: 320
27 Niewiarowski S, Farbiszewski R, Paplawski A. Neutralization of antithrombin VI (fibrinogen breakdown products) with platelet antiheparin factor (platelet factor 4). Thrombos. Diathes. haemorrh 1965; 14: 491-499
28 Niewiarowski S, Batallo Z, Stachurska J. Un nouvel inhibiteur de la génération de thromboplastine - I. G. T. - Produit au cours de la dégradation protéolytique du fibrinogène. Sang 1959; 30: 376
29 Nussenzweig V, Seligman M, Belmont J, Grabar P. Les produits de dégradation du fibrinogène humain par la plasmine, I. Separation et propriétés physicochimiques. Ann. Inst. Pasteur 1961; 100: 377-389
30 Rapaport S.I, Jonathan-Aas S, Owren P.A. The lipid inhibitor of brain Mechanism of its anticoagulant action and its comparison with soybean inositol phosphatide inhibitor. J. Lab. clin. Med 1954; 44: 364-373
31 Sanchez-Avalos J, Miller S.P. Degradation of fibrinogen by proteolytic enzymes, I. Characterization and isolation of products and their relation to fibrinolytic states. Thrombos. Diathes. haemorrh. (Stuttg.) 1968; 19: 499-515
32 Silver A, Murray M. The kinetics of inhibition of the action of thrombin by the fibrinopeptides formed during the clotting of fibrinogen. Thrombos. Diathes. haemorrh 1966; 16: 277
33 Triantaphyllopoulos D.G. Anticoagulant effect of incubated fibrinogen. Canad. J. Biochem. Phys 1958; 56: 249-259
34 Triantaphyllopoulos D. Anticoagulant action of TAMe and AFIF. Amer. J. Phys 1961; 200: 771
35 Triantaphyllopoulos D.C. AFIF inhibitor from fibrinogen. Thrombos. Diathes. haemorrh 1962; 7: 79-88 Suppl. 1
36 Triantaphyllopoulos E. D.G. Triantaphyllopoulos : Coagulation studies on the electrophoretic fractions of AFIF. Amer. J. Phys 1962; 203: 595
37 Triantaphyllopoulos E. D.G. Triantaphyllopoulos : Variability of the anticoagulant fraction of incubated fibrinogen. Amer. J. Phys 1965; 208: 521