Thromb Haemost 2003; 89(05): 832-836
DOI: 10.1055/s-0037-1613469
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Measurement of soluble fibrin monomer-fibrinogen complex in plasmas derived from patients with various underlying clinical situations

Kunihiko Nakahara
1   Iatron Laboratories, Inc., Chiba, Japan
,
Yumiko Kazahaya
1   Iatron Laboratories, Inc., Chiba, Japan
,
Yuichi Shintani
1   Iatron Laboratories, Inc., Chiba, Japan
,
Kensuke Yamazumi
2   First Department of Surgery, Kagoshima University, Kagoshima, Japan
,
Yutaka Eguchi
3   Intensive Care Unit, Shiga University of Medical Science, Shiga, Japan
,
Shin Koga
4   Division of Hematology and Immunology, Amakusa Chuo General Hospital, Kumamoto, Japan
,
Hideo Wada
5   Department of Clinical Laboratory, Mie University School of Medical, Mie, Japan
,
Michio Matsuda
6   Ogata Institute for Medical and Chemical Research, Tokyo, Japan
› Author Affiliations
Further Information

Publication History

Received 01 November 2002

Accepted after revision 18 February 2003

Publication Date:
09 December 2017 (online)

Summary

We previously reported a monoclonal antibody named IF-43 that specifically recognizes thrombin-modified fibrinogen (desAA- and desAABB- fibrin monomer) bound with fibrinogen or other D1 domain-containing plasmic fragments such as fragments X, Y, and D1, but not intact fibrinogen or cross-linked fibrin degradation products (XDP). Here, we tentatively named such complexes, soluble fibrin monomer (FM) -fibrinogen complex.

By utilizing IF-43, we have developed a kit to measure soluble FM-fibrinogen complex and compared the profiles with those of two established molecular markers for thrombo-embolic disorders: i.e. the thrombin-antithrombin complex (TAT) and the D-dimer in plasma of patients who underwent surgery without any thrombo-embolic complications. The result indicated that soluble FM-fibrinogen complex is a distinct entity from the two established molecular markers. We have also attempted to observe their profiles in patients with the disseminated intravascular coagulation syndrome (DIC). Although the profiles of soluble FM-fibrinogen complex in individual patients appeared to vary from one patient to the other, the plasma level of soluble FM-fibrinogen complex was found to be increased at the initial phase of disseminated intravascular coagulation syndrome. Thus, the soluble FM-fibrinogen complex may serve as an independent molecular marker for the detection of thrombin generation and the diagnosis of thrombosis. The soluble FM-fibrinogen complex may also serve as a risk factor for thrombosis, because it may precipitate as insoluble complexes beyond its threshold in plasma, or when it is modified by thrombin.

Part of this paper was originally presented at the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

 
  • References

  • 1 Blombäck B, Hessel B, Hogg D, Thelkildsen L.. A two-step fibrinogen-fibrin transition in blood coagulation. Nature 1978; 275: 501-5.
  • 2 Doolittle RF, Bouma IIIBA, Strong D, Watt KWK.. The covalent structure of human fibrinogen. In: The Chemistry and Physiology of the Human Plasma Proteins. Bing DH.. ed New York: Pergamon Press; 1989: 77-95.
  • 3 Olexa SA, Budzynski AZ.. Evidence for four different polymerization sites involved in human fibrin formation. Proc Natl Acad Sci USA 1980; 77: 1374-8.
  • 4 Kudryk B, Collen D, Woods KR, Blombäck B.. Evidence for localization of polymerization sites in fibrinogen. J Biol Chem 1974; 249: 3322-5.
  • 5 Shainoff JR, Page IH.. Significance of cryopro-fibrin in fibrinogen-fibrin conversion. J Exp Med 1962; 116: 687-707.
  • 6 Brass EP.. et al. Fibrin formation: The role of the fibrinogen-fibrin complexes. Thromb Haemost 1976; 36: 37-48.
  • 7 Graeff H, Hafter R, Von Hugo R.. On soluble fibrinogen-fibrin complexes. Thromb Res 1979; 16: 575-6.
  • 8 Soe G, Kohno I, Inuzuka K, Itoh Y, Matsuda M.. A monoclonal antibody that recognizes a neo-antigen exposed in the E domain of fibrin monomer complexed with fibrinogen or its derivatives: Its application to the measurement of soluble fibrin in plasma. Blood 1996; 88: 2109-17.
  • 9 Matsuda M, Terukina S, Yamazumi K, Maekawa H, Soe G... A monoclonal antibody that recognizes the NH2-terminal conformation of fragment D. In: Fibrinogen 4. Current basic and clinical aspects. Matsuda M, Iwanaga S, Takada A, Henschen A.. eds Amsterdam, The Netherlands: Excerpta medica; 1990: 43-8.
  • 10 Shimada K, Ozawa T.. Evidence that cell surface heparan sulfate is involved in the high affinity thrombin binding to cultured porcine aortic endothelial cells. J Clin Invest 1985; 75: 1308-16.
  • 11 Suenson E, Bjerrum P, Holm A.. et al. The role of fragment X polymers in the fibrin enhancement of tissue plasminogen activator-catalyzed plasmin formation. J Biol Chem 1990; 265: 22228-37.
  • 12 Nieuwenhuizen W.. Fibrin-mediated plasminogen activation. Ann N Y Acad Sci 2001; 936: 237-46.
  • 13 Francis CW, Marder VJ, Barlow GH.. Plasmic degradation of crosslinked fibrin: Characterization of new macromolecular soluble complexes and a model of their structure. J Clin Invest 1980; 66: 1033-43.
  • 14 Marder VJ, Francis CW.. Plasmin degradation of cross-linked fibrin. Ann NY Acad Sci 1983; 408: 397-406.
  • 15 Olexa SA, Budzynski AZ.. Primary soluble plasmic degradation products of human cross-linked fibrin. Isolation and stoichiometry of the (DD)E. Biochemistry 1979; 18: 991-5.
  • 16 Olexa SA.. et al. Structure of fragment E species from human cross-linked fibrin. Biochemistry 1981; 20: 6139-45.
  • 17 McCarron BI, Marder VJ, Francis CW.. Reactivity of soluble fibrin assays with plasmic degradation products of fibrin and in patients receiving fibrinolytic therapy. Thromb Haemost 1999; 82: 1722.