Detection of Fibrinogen Degradation Products by Use of Antibody Coated Latex Particles

E. J Melliger

doi:10.1055/s-0038-1654136

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1970; 23(02): 211-227
DOI: 10.1055/s-0038-1654136

Originalarbeiten – Original Articles – Travaux Originaux

Schattauer GmbH

Detection of Fibrinogen Degradation Products by Use of Antibody Coated Latex Particles

The Possibilities and Limits of the Method

Authors

E. J Melliger

¹Blood Coagulation and Fibrinolysis Laboratory (Head: PD Dr. F. Duckert) of the University Department of Medicine (Head: Prof. Dr. F. Koller), Bürgerspital, Basel (Switzerland)

Abstract

Summary

A method for rapid determination of fibrinogen split products in human blood basing on agglutination of antibody coated latex particles is described. It’s sensitivity corresponds to that of Ouchterlony plates (17 μg/ml plasma). The result is available within 1 hr after drawing of blood. The method is semiquantitative with a at least as good reproducibility as the haemagglutination inhibition method. The reaction kinetics follow the principle of optimal proportion in a precipitin system.

46 healthy people and 36 patients with various diseases were tested with the described method. 3 controls and 12 patients gave positive agglutination reactions that could not be attributed to the presence of split products. The mechanism of these side reactions which could be distinguished from the reactions due to fibrinogen degradation products is discussed. In the plasma of 10 patients split products could be demonstrated by the latex agglutination technic which was also successfully used to control the course of chronic intravascular coagulation in a patient with disseminated cancer of stomach. On account of the obtained results the method can be recommended as a fairly sensitive screening test for rapid bedside detection of fibrinogen degradation products.

Full Text

References

References
1 Seegers W. H, Nieft M. L, Vandenbelt J. M. Decomposition products of fibrinogen and fibrin. Arch. Biochem 7: 15 1945;
2 Niewiarowski S, Kowalski E. Formation of an antithrombin like anticoagulant during proteolysis of fibrinogen. Bull. Acad. poi. Sci. Ser. Sc. Biol 5: 169 1957;
3 Niewiarowski S, Kowalski E. Un nouvel anticoagulant dérivé du fibrinogène. Rév. Hémat 13: 321 1958;
4 Triantaphyllopoulos D. G. Anticoagulant effect of incubated fibrinogen. Canad. J. Biochem 515: 249 1958;
5 Gajewski J, Alexander B. Effect of plasmin on fibrinogen an fibrin. Amer. J. Physiol 209: 79 1964;
6 Ferguson H. J. Assay of tryptase by lysis of fibrinogen. Proc. Soc. exp. Biol. (N. Y.) 52: 243 1943;
7 Pechet L, Alexander B. The effect of certain proteolytic enzymes on the thrombin-fibrinogen interaction. Biochemistry 1: 875 1962;
8 Bocha E, Silva M, Andrade S. O, Teixeira B. M. Coagulation defect in the shocks produced by trypsin, peptone and ascaris extracts. Exp. Med. Surg 4: 260 1946;
9 Barnhardt M. I. Importance of neutrophilic leukocytes in the resolution of fibrin. Fed. Proc 24: 846 1965;
10 Batnoff O. D. Studies on a proteolytic enzyme in human plasma: IV. The rate of lysis of plasma clots in normal and diseased individuals, with particular reference to hepatic disease. :Bull. Johns Hopk. Hosp 84: 29 1949;
11 Beaumont J. L, Beaumont V, Domart A. Recherches sur l’activité fibrinolytique spontanée du plasma dans les cirrhoses du foie. Rév. franç. Étud. clin. biol 1: 667 1956;
12 Sherry S, Lindemeyer R. I, Fletcher A. P, Alkjaersig N. Studies on enhanced fibrinolytic activity in man. J. clin. Invest 38: 810 1959;
13 Fearnley G. R, Ghakrabarti R. Pharmacological enhancement of fibrinolytic activity of blood. J. clin. Path 17: 328 1964;
14 Schneider G. L. Fibrination and defibrination, in: Physiologie und Pathologie der Blutgerinnung in der Gestationsperiode. F. K. Schattauer; Stuttgart: 1957
15 Pritchard J. A, Wright M. R. Pathogenesis of hypofibrinogenemia in placental abruption. New Engl. J. Med 261: 218 1959;
16 Soldier J. P, Mathey J, Le Bollock A. G, Daumet P, Fayet H. Syndromes hémorrhagiques mortels avec incoagulabilité totale par défibrination et avec fibrinolyse. 1. Au cours des exérèses pulmonaires. Rév. Hémat 7: 30 1952;
17 Bernard J, Mathé G, Boulay J, Ceoara B, Chomé J. La leucose aigue à promyelocytes. Etude portant sur 20 observations. Schweiz, med. Wschr 89: 604 1959;
18 Baker W. G, Bang N. U, Nachman R. L, Raafat F, Horowitz H. I. Hypofibrinogenemic hemorrhage in acute myelogenous leukemia treated with heparin. With autopsy findings of widespread intravascular clotting. Ann. intern. Med 61: 116 1964;
19 Verstraete M, Vermylen G, Vermylen J, Vandenbroucke J. Excessive consumption of blood coagulation components as cause of hemorrhagic diathesis. Amer. J. Med 38: 899 1965;
20 Tagnon H. J, Shulman P, Whitmore W. F, Kravitz S. C. The “hemorrhagic syndrome of metastatic prostatic cancer and it’s treatment. J. clin. Invest 31: 666 1952;
21 Zeh H, Ott H. Klinische Gesichtspunkte zur Entstehung der erworbenen Afibrinogenämie und Fibrinogenopenie mit hämorrhagischer Diathese. Acta haemat. (Basel) 12: 106 1954;
22 Frick P. G. Acute hemorrhagic syndrome with hypofibrinogenemia in metastatic cancer. Acta haemat. (Basel) 16: 12 1956;
23 Meikle W. A, Graybill J. R. Fibrinolysis and hemorrhage in a fatal case of heat stroke. New Engl. J.Med 276: 911 1967;
24 Ferreira H. C, Murat L. G. An immunological method for demonstrating fibrin degradation products in serum and its use in the diagnosis of fibrinolytic states. Brit. J. Haemat 9: 299 1963;
25 Nhehn 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 1: 313 1964;
26 Merskey C, 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;
27 Brinkhous K. M, Wright I. S, Koller F, Streuli F, Duckert F. (Ed.) Diffuse intravascular clotting. F. K. Schattauer; Stuttgart: 1969
28 Catt K. J, Hirsh J, Castelan D. J, Niall H. D, Tregear G. I. F. Radioimmunoassay of fibrinogen and its proteolysis products. Thrombos. Diathes. haemorrh. (Stuttg.) 20: 1 1968;
29 Nussenzweig V, Seligmann M, Pelmont J, Grabar P. Les produits de dégradation du fibrinogène humain par la plasmine. I. Séparation et propriétés physiochimiques. Ann. Inst. Pasteur 200: 377 1961;
30 Lewis J. H, Wilson J. H. Fibrinogen breakdown products. Amer. J. Physiol 207: 1053 1964;
31 Fletcher A. P, Alkjaersig N, Fisher S, Sherry S. The proteolysis of fibrinogen by plasmin: the identification of thrombin-clottable fibrinogen dervatives which polymerize abnormally. J. Lab. clin. Med 68: 780 1966;
32 Niléhn J.-E. Split products of fibrinogen after prolonged interaction with plasmin. Thrombos. Diathes. haemorrh. (Stuttg.) 18: 89 1967;
33 Triantaphyllopoidos E, and Triantaphyllopoulos D. C. Micromolecular fragments split from fibrinogen. Thrombos. Diathes. haemorrh. (Stuttg.) 18: 300 1967;
34 Kowalski E, Kopeć M, Wegrzynowicz Z. Influence of fibrinogen degradation products (FDP) on platelet aggregation, adhesiveness and viscous metamorphosis. Thrombos. Diathes. haemorrh. (Stuttg.) 10: 406 1964;
35 Jerushalmy Z, Zucker M. B. Some effects of fibrinogen degradation products (FDP) on blood platelets. Thrombos. Diathes. haemorrh. (Stuttg.) 15: 413 1966;
36 Kopeć M, Budzyński A, Stachurska J, Wegrzynowicz Z, Kowalski E. Studies on mechanism of interference by fibrinogen degradation products (FDP) with platelet function: role of fibrinogen in platelet atmosphere. Thrombos. Diathes. haemorrh. (Stuttg.) 15: 476 1966;
37 Niewiarowski S, Batallo Z, Stachurska J. Apparition d’un inhibiteur de la thromboplastino-formation au cours de la protéolyse du fibrinogène. Rév. Hémat 14: 118 1959;
38 Triantaphyllopoulos D. C, Triantaphyllopoulos E. Evidence of antithrombic activity of the anticoagulant fraction of incubated fibrinogen. Brit. J. Haemat 12: 145 1966;
39 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;
40 Salmon J. Étude immunochimique du fibrinogène et de ses dérivés. Clin. chim. Acta 4: 767 1959;
41 Nussenzweig V, Seligmann M. Analyse par des méthodes immunochimiques, de la dégradation par la plasmine du fibrinogène humain et de la fibrine a différantes stades. Rév. Hémat 15: 451 1960;
42 Nussenzweig V, Seligmann M, Grabar P. Les produits de dégradation du fibrinogène humain par la plasmine. II. Étude immunochimique: mise en évidence d’anticorps antifibri-nogène natif possédant des spécifités différantes. Ann. Inst. Pasteur 100: 491 1961;
43 Niléhn J. E. Separation and estimation of “split products” of fibrinogen and fibrin in human serum. Thrombos. Diathes. haemorrh. (Stuttg.) 18: 487 1967;
44 Lipiński B, Wegrzynowicz Z, Budzyński A. Z, Kopeć M, Batallo Z. S, Kowalski E. Soluble unclottable complexes formed in the presence of fibrinogen degradation products (FDP) during the fibrinogen-fibrin conversion and their potential significance in pathology. Thrombos. Diathes. haemorrh. (Stuttg.) 17: 65 1967;
45 Fox Jr. F. J, Wide L, Killander J, Gemzell G. Determination of fibrinogen and fibrinolysis products in human plasma by an immunological method. Scand. J. clin. Lab. Invest 17: 341 1965;
46 Ouchterlony O. Antigen-antibody reactions in gels. Acta pathol. microbiol. scand 26: 507 1949;
47 Scheidegger J. J. Une microméthode de l’immunoelectrophorèse. Int. Arch. Allergy 7: 103 1955;
48 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta haemat. (Basel) 17: 237 1957;
49 Gitlin D. Use of ultraviolet absorbtion spectroscopy in the quantitative precipitin reaction. J. Immunology 62: 437 1949;
50 Nichol J. G, Deutsch H. F. Biophysical studies of blood plasma proteins. VII. Separation of gammaglobulins from the sera of various animals. J. Amer. ehem. Soc 70: 80 1948;
51 Campbell D. H, Garvey J. S, Cremer N. E, Sussdorf D. H. (Ed.) Methods in Immunology. W. A. Benjamin Inc.; New York, Amsterdam: 1964
52 Singer J. M, Plotz C. M. The latex fixation test. I. Application to the serologic diagnosis of rheumatoid arthritis. Amer. J. Med 21: 88 1956;
53 Singer J. M, Altmann G, Oreskes J, Plotz C. M. The mechanism of paticulate carrier reactions. III. The stabilizing effect of serum proteins. Amer. J. Med 30: 772 1961;
54 Dean H. R, Webb R. A. The influence of optimal proportions of antigen and antibody in the serum precipitation reaction. J. Path. Bact 29: 473 1926;
55 Isizaka T, Isizaka K. Biological activities of aggregated gamma globulin I. Skin reactive and complement-fixing properties of heat denaturated gammaglobulin. Proc. Soc. exper. Biol. (N. Y.) 101: 845 1959;
56 Singer J. M, Altmann G, Goldenberg A, Plotz C. M. The mechanism of particulate carrier reactions with rheumatoid sera. II. Sensitizing capacity of various human gamma globulins for latex paticles. Arthr. Rheum 3: 515 1960;
57 Dresner E, Trombly P. The latex-fixation reaction in non-rheumatic diseases. New. Engl. J. Med 261: 981 1959;
58 Howell D. S, Malcolm J. M, Rike P. The F-II-agglutinating factors in serums of patients with non-rheumatic diseases. Amer. J. Med 29: 662 1960;
59 Bartfeld H. Incidence and significance of seropositive tests for rheumatoid factor in non-rheumatic disease. Ann. intern. Med 52: 1059 1960;
60 Ropartz C, Memet Y, Hurei R, Lenoir J. Présence d’une antiglobuline humaine dans le serum de sujets tuberculeux. Rév. franç. Étud. clin. Biol 3: 1083 1958;
61 Singer J. M, Plotz C. M, Peralta F. M, Lyons H. C. Presence of anti-gamma globulin factors in sera of patients with active pulmonary tuberculosis. Ann. int. Med 56: 545 1962;
62 Harter F, Dickgiesser F. Agglutination reactions with sensitized erythrocytes in chronic polyarthritis and other diseases. Deutsch. Arch, kl in. Med 200: 202 1953;
63 Peltier A, Christian C. L. The presence of the “rheumatoid factor” in sera from patients with syphilis. Arthr. and Rheum 2: 1 1959;
64 Cathcart E. S, Williams Jr. R. C, Ross S. H, Calkins E. Relationship of the latex fixation test to the clinical and serological manifestations of leprosy. Amer. J. Med 31: 758 1961;
65 Dresner E, Trombly P, O’Brien G. F. Latex fixation in nonrheumatic diseases. Clin. Res 7: 49 1959;
66 Ziff M. The agglutination reaction in rheumatoid arthritis. J. chron. Dis 5: 644 1957;
67 Williams R. C, Kunkel H. G. Rheumatoid factor, complement and conglutinin aberrations in patients with subacute bacterial endocarditis. J. clin. Invest 41: 666 1962;
68 Kunkel H. G, Simon H. J, Fudenberg H. Observations concerning positive serologic reactions for rheumatoid factor in certain patients with sarcoidosis and other hyperglobulinaemic states. Arthr. and Rheum 1: 289 1958;
69 Vierucci A. Gm groups and anti-Cm antibodies in children with Cooley’s anaemia. Vox Sang. (Basel) 10: 82 1965;
70 Ropartz C, Vierucci A, Rivat L, Rousseau P.-Y. Simultaneous presence of ant i-Gm and anti-Inv in a poly transfused patient. Rév. franç. Étud. clin. Biol 9: 977 1964;
71 Allen J. C, Kunkel H. G. Antibodies against gammaglobulin after repeated blood transfusions in man. J. clin. Invest 45: 29 1966;
72 Speiser P. Über Antikörperbildung von Säuglingen und Kleinkindern gegen mütterliches gamma-2-Globulin. Ein bisher unbekanntes, dem Erythroblastosemechanismus konträres Phänomen mit anscheinend immunogenetisch obligatem Charakter. Wien. med. Wschr 113: 966 1963;
73 Steinberg A, Wilson J. A. Hereditary globulin factors and immunotolerance in man. Science 140: 303 1963;
74 L’Oudin J. “Allotypic” de certains antigènes protéidiques du sérum. C. R. Ac ad. Sci. (Paris) 242: 2606 1956;