D-Dimers and Fibrin Degradation Products [CO002700]
Related Information
Synonyms D-Dimers; FBP; FDP; Fibrin Breakdown Products;
Fibrin Split Products; FSP
Applies to Fibrinolysis; Plasmin; Thrombin; Thrombolysis
Abstract Fibrinolysis is mediated by plasmin, which degrades
fibrin clots into D-dimers and fibrin degradation products (FDP).
Plasmin can also degrade intact fibrinogen, generating fibrinogen
degradation products (FDP) that are detected in FDP assays.
Specimen Plasma (some FDP assays require serum; the SimpliRed®
D-dimer assay uses whole blood)
Container One blue top (citrate) tube (some FDP serum assays
require special tubes that contain thrombin to clot the blood, and
a fibrinolysis inhibitor to prevent FDP formation in the test tube)
Collection Routine venipuncture. If multiple tests are being
drawn, draw blue top tubes after any red top tubes but before any
lavender top (EDTA), green top (heparin), or gray top (oxalate/fluoride)
tubes. Immediately invert tube gently at least 4 times to mix. Tubes
must be appropriately filled. Deliver tubes immediately to the laboratory.
Storage Instructions Separate plasma from cells as soon as
possible. Store plasma at room temperature for up to 8 hours, on
ice for up to 24 hours, or store frozen. (Serum: Once serum is obtained,
it may be refrigerated for up to 1 week, or it may be stored frozen.)
Causes for Rejection Clotted specimens are unsuitable for
plasma-based tests.
Turnaround Time Less than 1 day (latex agglutination methods
take less than 1 hour; standard ELISA methods take 5 hours; rapid
ELISA methods have been developed)
Reference Interval D-dimer: approximately <0.5 microg/mL;
FDP: approximately <5 microg/mL
Use D-dimers or FDP are part of a panel of tests required
for diagnosing DIC. In DIC, both thrombin and plasmin are generated,
causing an elevation in D-dimers and FDP. See Disseminated
Intravascular Coagulation Screen.
D-dimers assist with the diagnosis of deep venous thrombosis (DVT)
and pulmonary embolism (PE), but only if a very sensitive method
is used. If the test is positive in a patient suspected to have
DVT or PE, clinicians proceed with further diagnostic tests for
DVT or PE. If the test is negative, depending on the clinical situation
and the sensitivity of the D-dimer assay, DVT or PE is considered
unlikely and further diagnostic tests for DVT or PE might not be
pursued.1,2
Monitoring thrombolytic therapy is not routinely required. However,
if monitoring is desired, D-dimers or FDP are one of several tests
that can be performed to confirm that thrombolysis (fibrinolysis)
is occurring. D-dimers and FDP should become increased with thrombolytic
therapy.
Limitations D-dimers and FDP can become elevated whenever
the coagulation and fibrinolytic systems are activated. This occurs
in a variety of conditions, and therefore the tests are not specific
for any one diagnosis.
Manual latex agglutination and certain other methods are not sufficiently
sensitive to exclude the diagnosis of DVT or PE when the test result
is negative. Even with the most sensitive methods (eg, ELISA assays),
a patient with PE or DVT may test negative for D-dimers.
High rheumatoid factor (RF) levels may cause false-positive results
with some assays.
Methodology Assays are semiquantitative or quantitative immunoassays.
Latex agglutination: Patient plasma is mixed with latex
particles which are coated with monoclonal anti-FDP antibodies.3
If FDP are present in the patient plasma, the latex particles agglutinate
as FDP bind to the antibodies on the particles. These large agglutinated
clumps are detected visually by the technologist. Various dilutions
of patient plasma can be tested to provide an estimation of the
FDP titer (semiquantitative result). Latex agglutination assays
are also available for D-dimers. Automated, quantitative versions
of this assay are commercially available for D-dimers (MDA®
D-dimer, Organon Teknika; STA Liatest®, Diagnostica Stago),
in which the agglutination is detected turbidimetrically by a coagulation
analyzer rather than visually by a technologist.4,5
Enzyme-linked immunosorbent (ELISA) assays: Quantitative
ELISA assays are available for FDP, D-dimers, or fibrinogen degradation
products. An automated, rapid ELISA assay for D-dimers is available
(VIDAS®, bioMerieux Inc).1,2,6
Other methods: SimpliRed® D-dimer (American Diagnostica)
is a semiquantitative red blood cell agglutination assay that can
be performed on whole blood. Other methods have been developed that
are not yet available in the United States.
Additional Information A D-dimer is a specific FDP that is
formed only by plasmin degradation of fibrin, and not by plasmin
degradation of intact fibrinogen. Thus, the presence of D-dimers
indicates that fibrin has been formed and degraded. In contrast,
a positive FDP assay indicates that fibrin and/or fibrinogen is
being degraded by plasmin, because the FDP assay detects fibrin
degradation products, including D-dimers, and fibrinogen degradation
products. D-dimers and FDP can be positive with DIC or thrombosis,
including DVT, PE and myocardial infarction. They also may be positive
in liver disease due to decreased hepatic clearance. They can become
elevated postoperatively, and with significant bleeding, hemodialysis,
eclampsia, sickle cell crisis, and other conditions. Cancer patients
often have positive D-dimers and FDP, usually representing low-grade,
chronic DIC. D-dimers and FDP mildly increase in pregnancy.
In the past, FDP had to be performed on serum samples, because
the polyspecific antibodies cross-react with fibrinogen in plasma.
Fibrinogen is not present in serum because it has been converted
into fibrin clot, centrifuged, and discarded. Currently, monoclonal
antibodies specific for FDP, without cross-reactivity against fibrinogen,
allow the test to be performed in plasma. There is some evidence
that the older, serum-based assays are not as reliable as the newer,
plasma-based assays, because serum-based FDP may give low values
due to trapping of FDP in the clot, or high values due to generation
of FDP during clot formation.7
Footnotes
1. van der Graaf F, van den Borne H, van der Kolk M, et al, "Exclusion
of Deep Venous Thrombosis With D-Dimer testing. Comparison of 13
D-Dimer Methods in 99 Outpatients Suspected of Deep Venous Thrombosis
Using Venography as Reference Standard,"Thromb Haemost, 2000,
83(2):191-8.
2. Perrier A, Desmarais S, Miron MJ, et al, "Noninvasive Diagnosis
of Venous Thromboembolism in Outpatients,"Lancet, 1999, 353(9148):190-5.
3. Mirshahi M, Soria J, Soria C, et al, "A Latex Immunoassay of
Fibrin/Fibrinogen Degradation Products in Plasma Using a Monoclonal
Antibody,"Thromb Res, 1986, 44(6):715-28.
4. Escoffre-Barbe M, Oger E, Leroyer C, et al, "Evaluation of a
New Rapid D-Dimer Assay for Clinically Suspected Deep Venous Thrombosis
(Liatest® D-Dimer),"Am J Clin Pathol, 1998, 109(6):748-53.
5. Bates SM, Grand'Maison A, Johnston M, et al, "A Latex D-Dimer
Reliably Excludes Venous Thromboembolism,"Thromb Haemost,
1999, 82(Suppl):258.
6. Pittet JL, de Moerloose P, Reber G, et al, "VIDAS® D-Dimer:
Fast Quantitative ELISA for Measuring D-Dimer in Plasma,"Clin
Chem, 1996, 42(3):410-15.
7. Gaffney PJ and Perry MJ, "Unreliability of Current Serum Fibrin
Degradation Product (FDP) Assays,"Thromb Haemost, 1985, 53(3):301-302.
References
Freyburger G, Trillaud H, and Labrouche S, "D-Dimer Strategy in
Thrombosis Exclusion. A Gold Standard Study in 100 Patients Suspected
of Deep Venous Thrombosis or Pulmonary Embolism: 8 DD Methods Compared,"Thromb
Haemost, 1998, 79(1):32-7.
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