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Thromb Haemost 1983; 50(02): 591-594
DOI: 10.1055/s-0038-1665263
Original Article
Schattauer GmbH Stuttgart

Measurement of Crosslinked Fibrin Degradation Products – An Immunoassay Using Monoclonal Antibodies

M J Elms
1   The Department of Pathology, Royal Brisbane Hospital, Brisbane, Queensland, Australia
,
I H Bunce
1   The Department of Pathology, Royal Brisbane Hospital, Brisbane, Queensland, Australia
,
P G Bundesen
2   The Centre for Applied Immunology, School of Health Science, Queensland Institute of Technology, Brisbane, Australia
,
D B Rylatt
2   The Centre for Applied Immunology, School of Health Science, Queensland Institute of Technology, Brisbane, Australia
,
A J Webber
2   The Centre for Applied Immunology, School of Health Science, Queensland Institute of Technology, Brisbane, Australia
,
P P Masci
3   The University of Queensland, Department of Medicine, Princess Alexandra Hospital, Brisbane, Australia
,
A N Whitaker
3   The University of Queensland, Department of Medicine, Princess Alexandra Hospital, Brisbane, Australia
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 24. Mai 1983

Accepted 24. Juni 1983

Publikationsdatum:
18. Juli 2018 (online)

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Summary

We have prepared a monoclonal antibody which recognises an antigenic determinant on D dimer, a specific fragment resulting from the degradation of crosslinked fibrin. This antibody has been used in the development of an enzyme-linked immunoassay for D dimer and related degradation products containing crosslinked gamma-gamma chains, to provide a simple assay of circulating crosslinked fibrin degradation products suitable for clinical use. Since these crosslinked fibrin degradation products are characteristic of fibrinolysis, as distinct from fibrinogenolysis, their measurement should aid in the diagnosis, evaluation and monitoring of thrombotic and thrombolytic states. In preliminary studies, low concentrations of crosslinked fibrin derivatives were detected in normal sera. High levels were found in 30/30 patients with disseminated intravascular coagulation .and in the majority of patients having deep venous thrombosis or pulmonary embolism.

Keywords

Fibrinolysis - Fibrin crosslinking - D dimer - Monoclonal antibodies - Enzyme immunoassay - Intravascular coagulation
 

  • References

  • 1 Merskey C, Johnson AJ. The clinical significance of fibrinogen-fibrin- related antigen in serum. Scand J Haematol 1971; Suppl 13: 313-315
    PubMedGoogle Scholar
  • 2 Marder VJ, Shulman NR, Carroll WR. High molecular weight derivatives of human fibrinogen produced by plasmin: I. Physicochemical and immunological characterization. J Biol Chem 1969; 244: 2111-2119
    PubMedGoogle Scholar
  • 3 Gaffney PJ. Breakdown products of fibrin and fibrinogen: Molecular mechanisms and clinical implications. J Gin Pathol 1980; 33 Suppl 10-17
    PubMedGoogle Scholar
  • 4 Francis CW, Marder VJ, Martin SE. Structural analysis of the particulate clot and identification of new macromolecular-soluble complexes. Blood 1980; 56: 456-464
    PubMedGoogle Scholar
  • 5 Francis CW, Marder VJ, Barlow GH. Plasmic degradation of cross- linked fibrin: Characterization of new macromolecular soluble complexes and a model of their structure. J Gin Invest 1980; 66: 1033-1043
    PubMedGoogle Scholar
  • 6 Gaffney PJ, Brasher M. Subunit structure of the plasmin-induced degradation products of crosslinked fibrin. Biochim Biophys Acta 1973; 295: 308-313
    CrossrefPubMedGoogle Scholar
  • 7 Gaffney PJ, Lane DA, Kakkar VV, Brasher M. Characterisation of a soluble D dimer-E complex in crosslinked fibrin digests. Thromb Res 1975; 7: 89-99
    CrossrefPubMedGoogle Scholar
  • 8 Gaffney PJ. Subunit relationships between fibrinogen and fibrin degradation products. Thromb Res 1973; 2: 201-218
    CrossrefPubMedGoogle Scholar
  • 9 Olexa SA, Budzynski AZ, Marder VJ. Modification of high molecular weight plasmic degradation products of human crosslinked fibrin. Biochim Biophys Acta 1979; 576: 39-50
    CrossrefPubMedGoogle Scholar
  • 10 Haverkate F, Timan G. Protective effect of calcium in the plasmin degradation of fibrinogen and fibrin fragments D. Thromb Res 1977; 10: 803-812
    CrossrefPubMedGoogle Scholar
  • 11 Matsushima A, Takahama Y, Inada Y. Preparation of guinea pig antiserum to quantitate serum fragment D-dimer derived from crosslinked fibrin. Thromb Res 1982; 27: 111-115
    CrossrefPubMedGoogle Scholar
  • 12 Gaffney PJ. Distinction between fibrinogen and fibrin degradation products in plasma. Clin Chim Acta 1975; 65: 109-115
    CrossrefPubMedGoogle Scholar
  • 13 Lane DA, Preston FE, VanRoss ME, Kakkar VV. Characterization of serum fibrinogen and fibrin fragments produced during disseminated intravascular coagulation. Br J Haematol 1978; 40: 609-615
    CrossrefPubMedGoogle Scholar
  • 14 Whitaker AN, Rowe EA, Masci PP, Gaffney PJ. Identification of D dimer-E complex in disseminated intravascular coagulation. Thromb Res 1980; 18: 453-459
    CrossrefPubMedGoogle Scholar
  • 15 Merskey C, Johnson AJ, Harris JU, Wang MT, Swain S. Isolation of fibrinogen-fibrin related antigen from human plasma by immuno- affinity chromatography: Its characterization in normal subjects and in defibrinating patients with abruptio placentae and disseminated cancer. Br J Haematol 1980; 44: 655-670
    CrossrefPubMedGoogle Scholar
  • 16 Graeff H, Hafter R. Detection and relevance of crosslinked fibrin derivatives in blood. Sem Thromb Hemostas 1982; 8: 57-68
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 17 Yoshioka K, Mizuno S, Miyata H, Maki S. Distinction between fibrinogen and fibrin degradation products produced during disseminated intravascular coagulation in childhood. Eur J Pediatr 1982; 138: 46-48
    CrossrefPubMedGoogle Scholar
  • 18 Lee-Own V, Gordon YB, Chard T. The detection of neoantigenic sites on the D-dimer peptide isolated from plasmin digested cross linked fibrin. Thromb Res 1979; 14: 77-84
    CrossrefPubMedGoogle Scholar
  • 19 Clausen NT, Gormsen J. γ1-dimer antibody and its specificity against fibrinogen, FR-a and carboxymethylated chains from fibrinogen and cross-linked fibrin. Thrombos Diathes Haemorrh 1975; 34: 326
    PubMedGoogle Scholar
  • 20 Budzynski AZ, Marder VJ, Parker ME, Shames P, Brizuela BS, Olexa SA. Antigenic markers on fragment DD: A unique plasmic derivative of human crosslinked fibrin. Blood 1979; 54: 794-804
    PubMedGoogle Scholar
  • 21 Purves LR, Lindsey GG, Franks JJ. Sites of D-domain interaction in fibrin-derived D-dimer. Biochemistry 1980; 19: 4051-4058
    CrossrefPubMedGoogle Scholar
  • 22 Gaffney PJ. Molecular aspects of fibrinolysis. Ann NY Acad Sci 1981; 370: 551-567
    CrossrefPubMedGoogle Scholar
  • 23 Cierniewski CS, Janiak A, Nowak P, Augustyniak W. Reactivity of fibrinogen derivatives with antisera to human fibrin D-dimer and its γ - γ chain remnant. Thromb Haemostas 1982; 48: 33-37
    PubMedGoogle Scholar
  • 24 Whaun JM, Oski FA. Experience with disseminated intravascular coagulation in a children’s hospital. Can Med Assoc J 1972; 107: 963-967
    PubMedGoogle Scholar
  • 25 Lane DA, Scully MF, Kakkar VV. A method for characterising serum fibrinogen and fibrin degradation products. Thromb Res 1976; 9: 191-200
    CrossrefPubMedGoogle Scholar
  • 26 Laki K. The polymerization of proteins: The action of thrombin on fibrinogen. Arch Biochem 1951; 32: 317-324
    CrossrefPubMedGoogle Scholar
  • 27 Deutsch DG, Mertz ET. Plasminogen: Purification from human plasma by affinity chromatography. Science 1970; 170: 1095-1096
    CrossrefPubMedGoogle Scholar
  • 28 Bajaj SP, Mann KG. Simultaneous purification of bovine prothrombin and factor X: Activation of prothrombin by trypsin-activated factor X. J Biol Chem 1973; 248: 7729-7741
    CrossrefPubMedGoogle Scholar
  • 29 Chung SI, Folk JE. Kinetic studies with transglutaminase: The human blood enzymes (activated coagulation factor XIII) and the guinea pig hair follicle. J Biol Chem 1972; 247: 2798-2807
    PubMedGoogle Scholar
  • 30 Nilehn J-E. Split products of fibrinogen after prolonged interaction with plasmin. Thrombos Diathes Haemorrh 1967; 18: 89-100
    PubMedGoogle Scholar
  • 31 Catanzaro A, Hathaway G, Strathern J, Edgington T. Structure and in vivo behaviour of human fibrinogen fragment-D. Proc Soc Exp Biol Med 1972; 139: 1401-1406
    CrossrefPubMedGoogle Scholar
  • 32 Gaffney PJ, Lane DA, Brasher M. Soluble high-molecular-weight E fragments in the plasmin-induced degradation products of crosslinked human fibrin. Clin Sci Mol Med 1975; 49: 149-156
    PubMedGoogle Scholar
  • 33 Olexa SA, Budzynski AZ. Primary soluble plasmic degradation product of human cross-linked fibrin. Isolation and stoichiometry of the (DD)E complex Biochemistry 1979; 18: 991-995
    CrossrefPubMedGoogle Scholar
  • 34 Kelly KA, Lang PG, Bundesen PG, Holford-Stevens V, Bottcher R, Sehon AH. The development of radioallergosorbent test (RAST) for murine IgE antibodies. J Immunol Methods 1985; 39: 317-333
    PubMedGoogle Scholar
  • 35 Nakane PK, Kaiwoi A. Peroxidase-labelled antibody. A new method of conjugation J Histiochem Cytochem 1974; 22: 1084-1091
    PubMedGoogle Scholar
  • 36 Barbour HM. Development of an enzyme immunoassay for human placental lactogen using labelled antibodies. J Immunol Methods 1976; 11: 15-23
    CrossrefPubMedGoogle Scholar
  • 37 Lahiri B, Koehn JA, Canfield RA, Birken S, Lewis J. Development of an immunoassay for the COOH-terminal region of the gamma chains of human fibrin. Thromb Res 1981; 23: 103-112
    CrossrefPubMedGoogle Scholar
  • 38 Sobel JH, Birken S, Ehrlich P, Friedman R, Moustafa Z, Canfield RE. Characterization of a crosslink-containing fragment derived from the a polymer of human fibrin and its application in immunologic studies using monoclonal antibodies. Thromb Haemostas 1981; 46: 240 (Abstr.)
    PubMedGoogle Scholar
  • 39 Bynum LJ, Crotty CM, Wilson III JE. Diagnostic value of tests of fibrin metabolism in patients predisposed to pulmonary embolism. Arch Intern Med 1979; 139: 283-285
    CrossrefPubMedGoogle Scholar