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Thromb Haemost 2001; 85(04): 671-678
DOI: 10.1055/s-0037-1615652
Review Articles
Schattauer GmbH

The Fibrin Assay Comparison Trial (FACT)

Evaluation of 23 Quantitative D-dimer Assays as Basis for the Development of D-dimer Calibrators
Carl-Erik Dempfle
1   University of Heidelberg, Mannheim University Hospital, I. Department of Medicine, Mannheim, Germany
,
Sybille Zips
1   University of Heidelberg, Mannheim University Hospital, I. Department of Medicine, Mannheim, Germany
,
Hanimsah Ergül
1   University of Heidelberg, Mannheim University Hospital, I. Department of Medicine, Mannheim, Germany
,
Dieter L. Heene
1   University of Heidelberg, Mannheim University Hospital, I. Department of Medicine, Mannheim, Germany
,
FACT study group › Author Affiliations
Further Information

Publication History

Received 28 September 2001

Accepted after revision 27 November 2000

Publication Date:
08 December 2017 (online)

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Summary

Although D-dimer has gained widespread clinical use as a parameter for detection of in vivo fibrin formation, the issue of standardization of D-dimer assays remains to be resolved. The FACT study was performed to generate basic data for development of calibrators and standard preparations.

A set of 86 samples, including plasma samples from patients with DIC, DVT, and other clinical conditions, serial dilutions of pooled plasma samples, and plasma samples containing fibrinogen- and fibrin derivatives, were distributed to 12 manufacturers of D-dimer assays.

D-dimer assays differ concerning specificity for crosslinked fibrin, and preference for either high molecular weight fibrin complexes, or low molecular weight fibrin degradation products. Terminal plasmin digests of fibrin clots for calibration produce aberrant results in some assays, especially those with preference for high molecular weight crosslinked fibrin derivatives. The best conformity is achieved by the use of pooled plasma samples from patients with high levels of D-dimer antigen in plasma. In vitro preparations containing a comparable composition of fibrin derivatives to clinical plasma samples may also serve as reference material.

Keywords

Fibrinogen-fibrin degradation products - D-dimer - fibrinogen - fibrin - standardization
 

  • References

  • 1 Marder VJ, Francis CW. Plasmin degradation of cross-linked fibrin. Ann N Y Acad Sci 1983; 408: 397-406.
    CrossrefPubMedGoogle Scholar
  • 2 Whitaker AN, Rowe EA, Masci PP, Gaffney PJ. Identification of D-dimerE complex in disseminated intravascular coagulation. Thromb Res 1980; 18: 453-9.
    CrossrefPubMedGoogle Scholar
  • 3 Brenner B, Francis CW, Marder VJ. The role of soluble cross-linked fibrin in D dimer immunoreactivity of plasmic digests. J Lab Clin Med 1989; 113: 682-8.
    PubMedGoogle Scholar
  • 4 Pfitzner SA, Dempfle CE, Heene DL. Fibrin detected in plasma of patients with disseminated intravascular coagulation by fibrin-specific antibodies consists primarily of high molecular weight factor XIIIa-crosslinked and plasmin-modified complexes partially containing fibrinopeptide A. Thromb Haemost 1997; 78: 1069-78.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Walker JB, Nesheim ME. The molecular weights, mass distribution, chain composition, and structure of soluble fibrin degradation products released from fibrin clot perfused with plasmin. J Biol Chem 1999; 274: 5201-12.
    CrossrefPubMedGoogle Scholar
  • 6 Hillyard CJ, Blake AS, Wilson K, Rylatt DB, Miles S, Bunch R, Elms MJ, Barnes A, Bundesen PG. A latex agglutination assay for D dimer: evaluation and application to the diagnosis of thrombotic disease. Clin Chem 1987; 33: 1837-40.
    PubMedGoogle Scholar
  • 7 Rylatt DB, Blake AS, Cottis LE, Massingham DA, Fletcher WA, Masci PP, Whitaker AN, Elms M, Bunce I, Webber AJ. An immunoassay for human D dimer using monoclonal antibodies. Thromb Res 1983; 31: 767-78.
    CrossrefPubMedGoogle Scholar
  • 8 Elms MJ, Bunce IH, Bundesen PG, Rylatt DB, Webber AJ, Masci PP, Whitaker AN. Measurement of crosslinked fibrin degradation products - an immunoassay using monoclonal antibodies. Thromb Haemost 1983; 50: 591-4.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Pittet JL, de Moerloose P, Reber G, Durand C, Villard C, Piga N, Rolland D, Comby S, Dupuy G. VIDAS D-dimer: fast quantitative ELISA for measuring D-dimer in plasma. Clin Chem 1996; 42: 410-5.
    PubMedGoogle Scholar
  • 10 Villa P, Ferrando F, Serra J, Faus H, Mira Y, Vaya A, Aznar J. Quantification of D-dimer using a new fully automated assay: its application for the diagnosis of deep vein thrombosis. Haematologica 2000; 85: 520-4.
    PubMedGoogle Scholar
  • 11 Keeling DM, Wright M, Baker P, Sackett D. D-dimer for the exclusion of venous thromboembolism: comparison of a new automated latex particle immunoassay (MDA D-dimer) with an established enzyme-linked fluorescent assay (VIDAS D-dimer). Clin Lab Haematol 1999; 21: 359-62.
    CrossrefPubMedGoogle Scholar
  • 12 Duet M, Benelhadj S, Kedra W, Vilain D, Ajzenberg C, Elkharrat D, Drouet L, Soria C, Mundler O. A new quantitative D-dimer assay appropriate in emergency: reliability of the assay for pulmonary embolism exclusion diagnosis. Thromb Res 1998; 91: 1-5.
    CrossrefPubMedGoogle Scholar
  • 13 Knecht MF, Heinrich F. Clinical evaluation of an immunoturbidimetric D-dimer assay in the diagnostic procedure of deep vein thrombosis and pulmonary embolism. Thromb Res 1997; 88: 413-7.
    CrossrefPubMedGoogle Scholar
  • 14 Gogstad GO, Dale S, Brosstad F, Brandsnes O, Holtlund J, Mork E, Gartner E, Borch SM. Assay of D-dimer based on immunofiltration and staining with gold colloids. Clin Chem 1993; 39: 2070-6.
    PubMedGoogle Scholar
  • 15 Vissac AM, Grimaux M, Chartier S, Chan FA, Chambrette B, Amiral J. A new sensitive membrane based ELISA technique for instantaneous D-Dimer evaluation in emergency. Thromb Res 1995; 78: 341-52.
    CrossrefPubMedGoogle Scholar
  • 16 Gaffney PJ, Edgell T, Creighton Kempsford LJ, Wheeler S, Tarelli E. Fibrin degradation product (FnDP) assays: analysis of standardization issues and target antigens in plasma. Br J Haematol 1995; 90: 187-94.
    CrossrefPubMedGoogle Scholar
  • 17 Nieuwenhuizen W. A reference material for harmonisation of D-dimer assays. Fibrinogen Subcommittee of the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis. Thromb Haemost 1997; 77: 1031-3.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Bradford M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-54.
    CrossrefPubMedGoogle Scholar
  • 19 Haddox MK, Russell DH. Increased nuclear conjugated polyamines and transglutaminase during livere regeneration. Proc Natl Acad Sci USA 1981; 78: 1712-6.
    CrossrefPubMedGoogle Scholar
  • 20 Freyburger G, Trillaud H, Labrouche S, Gauthier P, Javorschi S, Bernard P, Grenier N. D-dimer strategy in thrombosis exclusion. A gold standard study in 100 patients suspected of venous thrombosis or pulmonary embolism: 8 DD methods compared. Thromb Haemost 1998; 79: 32-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 van der Graaf F, Van den Borne H, Van der Kolk M, De Wild PJ, Janssen GWT, Van Uum SHM. Exclusion of Deep venous thrombosis with D-Dimer testing. Comparison of 13 D-Dimer methods in 99 outpatients suspected of venous thrombosis using venography as reference standard. Thromb Haemost 2000; 83: 191-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Ellis DR, Eaton AS, Plank MC, Butman BT, Ebert RF. A comparative evaluation of ELISAs for D-dimer and related fibrin(ogen) degradation products. Blood Coagul Fibrinolysis 1993; 4: 537-49.
    CrossrefPubMedGoogle Scholar
  • 23 Lorente JA, Garcia Frade LJ, Landin L, de Pablo R, Torrado C, Renes E, Garcia Avello A. Time course of hemostatic abnormalities in sepsis and its relation to outcome. Chest 1993; 103: 1536-42.
    CrossrefPubMedGoogle Scholar
  • 24 Kornberg A, Francis CW, Marder VJ. Plasma crosslinked fibrin polymers: Quantitation based on tissue plasminogen activator conversion to D-dimer and measurement in normals and patients with acute thrombotic disorders. Blood 1992; 80: 709-17.
    PubMedGoogle Scholar
  • 25 Adema E, Gebert U. Pooled patient samples as reference material for D-Dimer. Thromb Res 1995; 80: 85-8.
    CrossrefPubMedGoogle Scholar