D-dimer is a fibrin degradation product, a small protein fragment present in the blood
after a blood clot is degraded by fibrinolysis.
It is so named because it contains two crosslinked D fragments of the fibrin protein.
D-dimer concentration may be determined by a blood test to help diagnose thrombosis.
Since its introduction in the 1990s, it has become an important test performed in patients
with suspected thrombotic disorders.
While a negative result practically rules out thrombosis, a positive result can indicate
thrombosis but does not rule out other potential causes.
Its main use, therefore, is to exclude thromboembolic disease where the probability is low.
In addition, it is used in the diagnosis of the blood disorder disseminated intravascular
coagulation.
Principles
Coagulation, the formation of a blood clot or thrombus, occurs when the proteins of the
coagulation cascade are activated, either by contact with damaged blood vessel wall
or by activation of factor VII by tissue activating factors.
Both pathways lead to the generation of thrombin, an enzyme that turns the soluble blood protein
fibrinogen into fibrin, which aggregates into proteofibrils.
Another thrombin-generated enzyme, factor XIII, then crosslinks the fibrin proteofibrils
at the D fragment site, leading to the formation of an insoluble gel which serves as a scaffold
for blood clot formation.
The circulating enzyme plasmin, the main enzyme of fibrinolysis, cleaves the fibrin gel in
a number of places.
The resultant fragments, "high molecular weight polymers", are digested several times more
by plasmin to lead to intermediate and then to small polymers.
The cross-link between two D fragments remains intact, however, and these are exposed on
the surface when the fibrin fragments are sufficiently digested.
The typical D-dimer containing fragment contains two D domains and one E domain of the original
fibrinogen molecule.
D-dimers are not normally present in human blood plasma, except when the coagulation
system has been activated, for instance because of the presence of thrombosis or disseminated
intravascular coagulation.
The D-dimer assay depends on the binding of a monoclonal antibody to a particular epitope
on the D-dimer fragment.
Several detection kits are commercially available; all of them rely on a different monoclonal
antibody against D-dimer.
For some of these, the area of the D-dimer to which the antibody binds is known.
The binding of the antibody is then measured quantitatively by one of various laboratory
methods.
Indications D-dimer testing is of clinical use when there
is a suspicion of deep venous thrombosis, pulmonary embolism or disseminated intravascular
coagulation.
It is under investigation in the diagnosis of aortic dissection.
For DVT and PE, there are possible various scoring systems that are used to determine
the a priori clinical probability of these diseases; the best-known were introduced by
Wells et al..
For a very high score, or pretest probability, a D-dimer will make little difference and
anticoagulant therapy will be initiated regardless of test results, and additional testing for
DVT or pulmonary embolism may be performed.
For a moderate or low score, or pretest probability:A negative D-dimer test will virtually rule
out thromboembolism: the degree to which the D-dimer reduces the probability of thrombotic
disease is dependent on the test properties of the specific test used in the clinical
setting: most available D-dimer tests with a negative result will reduce the probability
of thromboembolic disease to less than 1% if the pretest probability is less than 15-20%
If the D-dimer reads high, then further testing is required to confirm the presence of thrombus.
Anticoagulant therapy may be started at this point or withheld until further tests confirm
the diagnosis, depending on the clinical situation.
In some hospitals, they are measured by laboratories after a form is completed showing the probability
score and only if the probability score is low or intermediate.
This reduces the need for unnecessary tests in those who are high-probability.
Performing the D-dimer test first can avoid a significant proportion of imaging tests
and is less invasive.
Since the D-dimer can exclude the need for imaging, specialty professional organizations
recommend that physicians use D-dimer testing as an initial diagnostic.
Test properties Various kits have a 93-95% sensitivity and
about 50% specificity in the diagnosis of thrombotic disease.
False positive readings can be due to various causes: liver disease, high rheumatoid factor,
inflammation, malignancy, trauma, pregnancy, recent surgery as well as advanced age.
False negative readings can occur if the sample is taken either too early after thrombus formation
or if testing is delayed for several days.
Additionally, the presence of anti-coagulation can render the test negative because it prevents
thrombus extension.
False values may be obtained if the specimen collection tube is not sufficiently filled.
This is due to the dilutional effect of the anticoagulant.
Likelihood ratios are derived from sensitivity and specificity to adjust pretest probability.
In interpretation of the d-dimer, for patients over age 50 a value of ageX10 may be abnormal.
History D-dimer was originally described in the 1970s,
and found its diagnostic application in the 1990s.
References
External links D-dimer - Lab Tests Online