Thromb Haemost 2004; 91(04): 812-818
DOI: 10.1160/TH03-09-0577
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Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score

Carl-Erik Dempfle
1   University Hospital of Mannheim, I.Department of Medicine, Mannheim, Germany
,
Michael Wurst
1   University Hospital of Mannheim, I.Department of Medicine, Mannheim, Germany
,
Mathias Smolinski
1   University Hospital of Mannheim, I.Department of Medicine, Mannheim, Germany
,
Stephan Lorenz
1   University Hospital of Mannheim, I.Department of Medicine, Mannheim, Germany
,
Alexandra Osika
2   University Hospital of Mannheim, Institute for Anaesthesiology and Operative Intensive Care, Mannheim, Germany
,
Daniela Olenik
2   University Hospital of Mannheim, Institute for Anaesthesiology and Operative Intensive Care, Mannheim, Germany
,
Fritz Fiedler
2   University Hospital of Mannheim, Institute for Anaesthesiology and Operative Intensive Care, Mannheim, Germany
,
Martin Borggrefe
1   University Hospital of Mannheim, I.Department of Medicine, Mannheim, Germany
› Author Affiliations
Further Information

Publication History

Received 16 September 2003

Accepted after resubmission 23 March 2003

Publication Date:
06 December 2017 (online)

Summary

The overt DIC score of the DIC subcommittee of the ISTH includes a fibrin-related marker (FRM) as indicator of intravascular fibrin formation. The type of marker to be used has not been specified, but D-dimer antigen, or fibrin degradation products are used by most investigators. Soluble fibrin complexes have been suggested as more specific indicators of acute intravascular fibrin formation. The aim of the present study was to compare the predictive value of the overt DIC score concerning clinical outcome in a surgical intensive care cohort, using either D-dimer antigen, or soluble fibrin antigen as FRM. The cutoff values for 2 and 3 score points for the FRM were assigned on the basis of the 25% and 75% quartiles of 1870 plasma samples obtained from 359 ICU patients during a period of 6 months. For 331 patients with complete diagnostic workup and day 1 blood samples, the Iatro SF as FRM component of the overt DIC score displayed the highest prognostic power concerning clinical outcome. The 28-day mortality of patients with overt DIC at day 1, using Iatro SF as FRM assay was 50.0%, whereas 28-day mortality of patients without overt DIC was 14.0% (p <0.0001). Using MDA D-dimer, and TINAquant D-dimer, 28-day mortality was between 35.5% and 39.3% in patients with overt DIC, and 15.5% to 15.6% in patients without overt DIC. Selection of the FRM as component of the DIC score has a small, but relevant impact on the prognostic performance of the overt DIC score. The present data on the distribution of values may provide a basis for the selection of appropriate cutoff points for assigning 2, and 3 points in the score.

 
  • References

  • 1 Taylor Jr FB, Toh CH, Hoots WK. et al. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 2001; 86: 1327-30.
  • 2 Greenberg CS, Achyuthan KE, Rajagopalan S. et al. Characterization of the fibrin polymer structure that accelerates thrombin cleavage of plasma factor XIII. Arch Biochem Biophys 1988; 262: 142-8.
  • 3 Yakovlev S, Makogonenko E, Kurochkina N. et al. Conversion of fibrinogen to fibrin: mechanism of exposure of tPA-and plasminogen-binding sites. Biochemistry 2000; 39: 15730-41.
  • 4 Mosesson MW, Siebenlist KR, Voskuilen M. et al. Evaluation of the factors contributing to fibrin-dependent plasminogen activation. Thromb Haemost 1998; 79: 796-801.
  • 5 Shainoff JR, DiBello PM. The circulatory half-lives of alpha-profibrin and alpha-fibrin monomer, and comparisons with other fibrin(ogen) derivatives. Thromb Haemost 2003; 89: 48-52.
  • 6 Pfitzner SA, Dempfle CE, Matsuda M. et al. Fibrin detected in plasma of patients with disseminated intravascular coagulation by fibrinspecific antibodies consists primarily of high molecular weight factor XIIIa-crosslinked and plasmin-modified complexes partially containing fibrinopeptide A. Thromb Haemost 1997; 78: 1069-78.
  • 7 Gaffney PJ, Edgell T, Creighton-Kempsford LJ. et al. Fibrin degradation product (FnDP) assays: analysis of standardization issues and target antigens in plasma. Br J Haematol 1995; 90: 187-94.
  • 8 Soe G, Kohno I, Inuzuka K. et al. 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 Nakahara K, Kazahaya Y, Shintani Y. et al. Measurement of soluble fibrin monomerfibrinogen complex in plasmas derived from patients with various underlying clinical situations. Thromb Haemost 2003; 89: 832-6.
  • 10 Bone RC, Balk RA, Cerra FB. et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992; 101: 1644-55.
  • 11 Levy MM, Fink MP, Marshall JC. et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31: 1250-6.
  • 12 Godal HC, Abildgaard U. Gelation of soluble fibrin in plasma by ethanol. Scand J Haematol 1966; 03: 342-50.
  • 13 Lipinski B, Worowski K. Detection of soluble fibrin monomer complexes in blood by means of protamine sulphate test. Thromb Diath Haemorrh 1968; 20: 44-49.
  • 14 Largo R, Heller V, Straub PW. Detection of soluble intermediates of the fibrinogen-fibrin conversion using erythrocytes coated with fibrin monomers. Blood 1976; 47: 991-1002.
  • 15 Oehler G, Klaus H, Stotzer KE, Spanuth E. Detection of soluble fibrin monomer complexes. Comparison of a haemagglutination assay with the ethanol gelation test. Folia Haematol Int Mag Klin Morphol Blutforsch 1988; 115: 278-83.
  • 16 Halvorsen S, Skjonsberg OH, Godal HC. The stimulatory effect of soluble fibrin on plasminogen activation by tissue plasminogen activator as studied by the Coa-set Fibrin Monomer test. Thromb Res 1991; 61: 453-61.
  • 17 Scheefers-Borchel U, Muller-Berghaus G, Fuhge P. et al. Discrimination between fibrin and fibrinogen by a monoclonal antibody against a synthetic peptide. Proc Natl Acad Sci U S A 1985; 82: 7091-5.
  • 18 Lill H, Spannagl M, Trauner A. et al. A new immunoassay for soluble fibrin enables a more sensitive detection of the activation state of blood coagulation in vivo . Blood Coagul Fibrinolysis 1993; 04: 97-102.
  • 19 Dempfle CE, Dollman M, Lill H. et al. Binding of a new monoclonal antibody against N-terminal heptapeptide of fibrin alpha-chain to fibrin polymerization site ‘A’: effects of fibrinogen and fibrinogen derivatives, and pretreatment of samples with NaSCN. Blood Coagul Fibrinolysis 1993; 04: 79-86.
  • 20 Nieuwenhuizen W, Hoegee-De Nobel E, Laterveer R. A rapid monoclonal antibodybased enzyme immunoassay (EIA) for the quantitative determination of soluble fibrin in plasma. Thromb Haemost 1992; 68: 273-277.
  • 21 Okajima K, Uchiba M, Murakami K. et al. Determination of plasma soluble fibrin using a new ELISA method in patients with disseminated intravascular coagulation. Am J Hematol 1996; 51: 186-91.
  • 22 Hamano A, Tanaka S, Takeda Y. et al. A novel monoclonal antibody to fibrin monomer and soluble fibrin for the detection of soluble fibrin in plasma. Clin Chim Acta 2002; 318: 25-32.
  • 23 Carville DG, Dimitrijevic N, Walsh M. et al. Thrombus precursor protein (TpP): marker of thrombosis early in the pathogenesis of myocardial infarction. Clin Chem 1996; 42: 1537-41.
  • 24 Gargan PE, Ploplis VA, Scheu JD. A fibrin specific monoclonal antibody which interferes with the fibrinolytic effect of tissue plasminogen activator. Thromb Haemost 1988; 59: 426-31.