The Fibrin Assay Comparison Trial (FACT): Correlation of Soluble Fibrin Assays with D-dimer

Summary

Soluble fibrin (SF) is regarded as an indicator of acute fibrin formation and a precursor of fibrin thrombi. Using a set of clinical plasma samples, and fibrin derivatives, five assays for measurement of SF, including two chromogenic assays, two ELISA systems, and one latex-enhanced photometric immunoassay were compared. Correlation between SF assays was moderate (Spearman’s rho values between 0.344 and 0.805). Re-calibration with serial dilutions of desAABBfibrin monomer resulted in adjustment of the numerical scale of the assays without improving correlation.

All SF assays reacted with purified crosslinked fibrin derivatives. Using clinical plasma samples, Spearman’s rho of SF assays with D-dimer consensus values based upon results of 23 quantitative D-dimer assays were between 0.491 and 0.911.

Although all SF assays react with desAABB-fibrin monomer complexes, SF assays are heterogeneous concerning reactivity with fibrin compounds observed in clinical plasma samples. The prospect of a common calibrator for SF assays therefore seems to be remote.

Since SF assays react with crosslinked fibrin derivatives, it is not possible to clearly distinguish between acute fibrin formation, and fibrin dissolution on the basis of the results of current SF assays.

Keywords

Fibrin - fibrinogen degradation products - fibrin monomer - assay - standardization

• References

• 1 Wiman B, Ranby M. Determination of soluble fibrin in plasma by a rapid and quantitative spectrophotometric assay. Thromb Haemost 1986; 55: 189-93.
• 2 Lill H, Spannagl M, Trauner A, Schramm W, Schuller D, Ofenloch Haehnle B, Draeger B, Naser W, Dessauer A. A new immunoassay for soluble fibrin enables a more sensitive detection of the activation state of blood coagulation in vivo. Blood Coagul Fibrinolysis 1993; 4: 97-102.
• 3 Dempfle CE, Dollman M, Lill H, Puzzovio D, Dessauer A, Heene DL. Binding of a new monoclonal antibody against N-terminal heptapeptide of fibrin a-chain to fibrin polymerization site “A”: effects of fibrinogen and fibrinogen derivatives, and pretreatment of samples with NaSCN. Blood Coagul Fibrinolysis 1993; 4: 79-86.
• 4 Schielen WJ, Voskuilen M, Tesser GI, Nieuwenhuizen W. The sequence A a-(148-160) in fibrin, but not in fibrinogen, is accessible to monoclonal antibodies. Proc Natl Acad Sci USA 1989; 86: 8951-4.
• 5 Schielen WJ, Adams HP, Van Leuven K, Voskuilen M, Tesser GI, Nieuwenhuizen W. The sequence γ-(312-324) is a fibrin-specific epitope. Blood 1991; 77: 2169-73.
• 6 Nieuwenhuizen W, Hoegee-de Nobel E, Laterveer R. A rapid monoclonal antibody-based enzyme immunoassay (EIA) for the quantitative determination of soluble fibrin in plasma. Thromb Haemost 1992; 68: 273-7.
• 7 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 complexes with fibrinogen or its derivatives: Its application to the measurement of soluble fibrin in plasma. Blood 1996; 88: 2109-17.
• 8 Dempfle CE, Pfitzner SA, Dollman M, Huck K, Stehle G, Heene DL. Comparison of immunological and functional assays for measurement of soluble fibrin. Thromb Haemost 1995; 74: 673-9.
• 9 Dempfle CE, Zips S, Ergül H, Heene DL. The fibrin assay comparison trial (FACT): Evaluation of 23 quantitative D-dimer assays as basis for the development of D-dimer calibrators. Thromb Haemost 2001; 85: 671-8.
• 10 McCarron BI, Marder VJ, Kanouse JJ, Francis CW. A soluble fibrin standard: comparable dose-response with immunologic and functional assays. . Thromb Haemost 1999; 82: 145-8.
• 11 Dempfle CE. The use of soluble fibrin in evaluating the acute and chronic hypercoagulable state. Thromb Haemost 1999; 82: 673-83.
• 12 Gargan PE, Gaffney PJ, Pleasants JR, Ploplis VA. A monoclonal antibody which recognizes an epitopic region unique to the intact fibrin polymeric structure. Fibrinolysis 1993; 7: 275-83.
• 13 Carville DG, Dimitrijevic N, Walsh M, Digirolamo T, Brill EM, Drew N, Gargan PE. Thrombus precursor protein (TpP): marker of thrombosis early in the pathogenesis of myocardial infarction. Clin Chem 1996; 42: 1537-41.
• 14 Greenberg CS, Achyuthan KE, Fenton JW. Factor XIIIa formation promoted by complexing of a-thrombin, fibrin, and plasma factor XIII. Blood 1987; 69: 867-71.
• 15 Suenson E, Petersen LC. Fibrin and plasminogen structures essential to stimulation of plasmin formation by tissue-type plasminogen activator. Biochim Biophys Acta 1986; 870: 510-9.
• 16 Brummel KE, Butenas S, Mann KG. An integrated study of fibrinogen during blood coagulation. J Biol Chem 1999; 274: 22862-70.
• 17 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.
• 18 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.
• 19 Suenson E, Bjerrum P, Holm A, Lind B, Meldal M, Selmer J, Petersen LC. The role of fragment X polymers in the fibrin enhancement of tissue plasminogen activator-catalyzed plasmin formation. J Biol Chem 1990; 265: 22228-37.
• 20 Mosesson MW, Siebenlist KR, Voskuilen M, Nieuwenhuizen W. Evaluation of the factors contributing to fibrin-dependent plasminogen activation. Thromb Haemost 1998; 79: 796-801.
• 21 Haddeland U, Bennick A, Brosstad F. Stimulating effect on tissue-type plasminogen activator-a new and sensitive indicator of denatured fibrinogen. Thromb Res 1995; 77: 329-36.
• 22 Stewart RJ, Fredenburgh JC, Rischke JA, Bajzar L, Weitz JI. Thrombinactivable fibrinolysis inhibitor attenuates DD(E)-mediated stimulation of plasminogen activation by reducing the affinity of DD(E) for tissue plasminogen activator. J Biol Chem 2000; 275: 36612-20.