D-Dimer Assays for the Exclusion of Venous Thromboembolism

ABSTRACT

Many assay systems for D-dimer measurement are available. Their intended use is mainly the exclusion of venous thromboembolism (VTE). Despite standardization attempts, an important variability in assay results is observed, and therefore data obtained by use of one assay cannot be extrapolated to another assay. As a consequence, each assay must be validated in appropriate clinical trials to determine its cut-off value for VTE exclusion. The differences observed can be explained by the heterogeneity of fibrin degradation products present in patient samples, by the reactivity of the various antibodies and their combinations, and by the differences in calibrators and in the format of assays. Among the different assay systems available, the use of automated, observer-independent tests having good analytical sensitivity is highly recommended. The assay should also exhibit a high sensitivity for VTE exclusion to be used as the first step of any diagnostic strategy.

Fibrin degradation products - fibrinogen - D-dimer - analysis - deep venous thrombosis - pulmonary embolism

REFERENCES

• 1 Eisenberg P R, Jaffe A S, Stump D C. Validity of enzyme-linked immunoadsorbent assays of cross-linked fibrin degradation products as a measure of clot lysis.  Circulation . 1990;  82 1159-1168
• 2 Caliezi C, Reber G, Lämmle B. Agreement of D-dimer results, measured by a rapid ELISA (VIDAS) before and after storage during 24 hours or transportation of the original whole blood samples.  Thromb Haemost . 2000;  83 177-178
• 3 Steiner J, Braun P, Byrd P. A comparison of three quantitative assays for fibrin degradation products and D-dimer (abstract).  Thromb Haemost . 1993;  69 835
• 4 Wylie F G, Walsh T P. Variable immunoreactivity of D-dimer preparations for monoclonal antibody DD-3B6/22.  Blood Coag Fibrinolysis . 1995;  6 738-742
• 5 Hart R, Bate I, Dihn D. The detection of d-dimer in plasma by enzyme immunoassay: improved discrimination is obtained with more specific signal antibody.  Blood Coag Fibrinolysis . 1994;  5 227-232
• 6 Elms M J, Bundesen P G, Rowbury D. Automated determination of cross-linked fibrin derivatives in plasma.  Blood Coag Fibrinolysis . 1993;  4 159-164
• 7 Amiral J, Minard F, Plassart V. Reactivity of D-dimer assays with the fibrinogen-fibrin split products generated by thrombolytic agents.  Blood Coag Fibrinolysis . 1990;  1 525-530
• 8 Ellis D R, Eaton A S, Plank M C. A comparative evaluation of ELISAs for D-dimer and related fibrin(ogen) degradation products.  Blood Coag Fibrinolysis . 1993;  4 537-549
• 9 Gogstad G O, Dale S, Brosstad F. Assay of D-dimer based on immunofiltration and staining with gold colloids.  Clin Chem . 1993;  30 2070-2076
• 10 Pittet J L, de Moerloose P, Reber G. VIDAS D-dimer: fast quantitative ELISA for measuring D-dimer in plasma.  Clin Chem . 1996;  42 410-415
• 11 Amiral J, Grosley M, Mimilla F. Monoclonal antibodies to different neo-epitopes on fibrinogen and fibrin degradation products.  Blood Coag Fibrinolysis . 1990;  1 447-452
• 12 Koppert P W, Koopman J, Haverkate F, Nieuwenhuizen W. Production and characterization of a monoclonal antibody reactive with a specific neoantigenic determinant (comprising Bβ 54-118) in degradation products of fibrin and fibrinogen.  Blood . 1986;  68 437-441
• 13 Koppert P W, Hoegee-de-Nobel E, Nieuwenhuizen W. A monoclonal antibody-based enzyme immunoassay for fibrin degradation products in plasma.  Thromb Haemost . 1988;  31 310-315
• 14 Koppert P W, Kuipers W, Hoegee-de-Nobel E. A quantitative enzyme immunoassay for primary fibrinogenolysis products in plasma.  Thromb Haemost . 1987;  57 25-28
• 15 Perrier A, Bounameaux H, Morabia A. Diagnosis of pulmonary embolism by a decision analysis-based strategy including clinical probability, D-dimer levels, and ultrasonography: a management study.  Arch Intern Med . 1996;  156 531-536
• 16 Perrier A, Desmarais S, Miron M J. Noninvasive diagnosis of venous thromboembolism in outpatients including clinical probability, D-dimer and ultrasonography.  Lancet . 1999;  353 190-195
• 17 Vissac A M, Grimaux M, Chartie S. A new sensitive membrane based ELISA technique for instantaneous D-dimer evaluation in emergency.  Thromb Res . 1995;  78 341-352
• 18 John M A, Elms M J, O'Reilly E J. The SimpliRed D-dimer test: a novel assay for the detection of cross-linked fibrin degradation products in whole blood.  Thromb Res . 1990;  58 273-278
• 19 Gaffney P J, Edgell T, Creighton-Kempsford L J. Fibrin degradation products assays: analysis of standardization issues and target antigens in plasma.  Br J Haematol . 1995;  90 187-194
• 20 Nieuwenhuizen W. A reference material for harmonisation of D-dimer assays.  Thromb Haemost . 1997;  77 1031-1033
• 21 Adema E, Gebert U. Pooled patient samples as reference material for D-dimer.  Thromb Res . 1995;  80 85-88
• 22 Bounameaux H, de Moerloose P, Perrier A, Miron M-J. D-dimer testing in suspected venous thromboembolism: an update.  Q J Med . 1997;  90 437-442
• 23 Ginsberg J S, Wells P S, Kearon C. Sensitivity and specificity of a rapid whole-blood assay for D-dimer in the diagnosis of pulmonary embolism.  Ann Intern Med . 1998;  129 1006-1011
• 24 Turkstra F, van Beek R J, Büller H R. Observer and biological variation of a rapid whole blood D-dimer.  Thromb Haemost . 1998;  79 91-93
• 25 Mauron T, Baumgartner I, Z'Brun A. SimpliRed D-dimer assay: comparability of capillary and citrated venous whole blood, between-assay variability, and performance of the test for exclusion of deep vein thrombosis in symptomatic outpatients.  Thromb Haemost . 1998;  79 1217-1219
• 26 Kraaijenhagen R A, te Lintelo O M, Vink R. The introduction of the SimpliRed D-dimer assay and a clinical decision rule in a general practise setting. A pilot study (abstract).  Thromb Haemost . 1999;  (Suppl) 174