D-dimer

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D-dimer (or D dimer) is a

dimer that is a fibrin degradation product (or FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two D fragments of the fibrin protein joined by a cross-link, hence forming a protein dimer.[1]

D-dimer concentration may be determined by a

venous thromboembolism.[2][3] While a negative result practically rules out thrombosis, a positive result can indicate thrombosis but does not exclude other potential causes.[3] Its main use, therefore, is to exclude thromboembolic disease where the probability is low.[1][2]

D-dimer levels are used as a predictive

COVID-19 infection.[1][3] A four-fold increase in the protein is an indicator of poor prognosis in people hospitalized with COVID-19.[1][3][4]

Principles

fibrin degradation products (FDPs), the smallest of which are D-dimers, protein fragments with one E and two crosslinked D domains from an original fibrinogen.[1][5]

factor VII by tissue activating factors (extrinsic pathway). Both pathways lead to the generation of thrombin, an enzyme that turns the soluble blood protein fibrinogen into fibrin, which aggregates into protofibrils. Another thrombin-generated enzyme, factor XIII, then crosslinks the fibrin protofibrils at the D fragment site, leading to the formation of an insoluble gel that serves as a scaffold for blood clot formation.[1]

The circulating enzyme

kDa[6] or 195 kDa[7] molecule of two D domains, or a 340 kDa[7] molecule of two D domains and one E domain of the original fibrinogen molecule.[1] The half-life of D-dimer in blood is approximately 6 to 8 hours.[8]

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.[1]

Indications

D-dimer testing is of clinical use when there is a suspicion of

deep venous thrombosis (DVTl), pulmonary embolism (PE) or disseminated intravascular coagulation (DIC).[1][3]

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 is the Wells score.[5]

  • For a 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:[citation needed]

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.

professional organizations recommend that physicians use D-dimer testing as an initial diagnostic.[12][13][14][15]

Interpretation

Reference ranges

The following are reference ranges for D-dimer:[16]

Units Nonpregnant
adult
First trimester Second trimester Third trimester
mg/L or µg/mL < 0.5 0.05 - 0.95 0.32 - 1.29 0.13 -1.7
µg/L or ng/mL < 500 50 - 950 320 - 1290 130 - 1700
nmol/L < 2.7 0.3 - 5.2 1.8 - 7.1 0.7 - 9.3

D-dimer increases with age. It has therefore been suggested to use a cutoff equal to patient’s age in years × 10 µg/L (or x 0.056 nmol/L) for patients aged over 50 years for the suspicion of venous thromboembolism (VTE), as it decreases the

false negative rate.[17][18]

An alternative measurement of D-dimer is in fibrinogen equivalent units (FEU). The molecular weight of the fibrinogen molecule is about twice the size of the D-dimer molecule, and therefore 1.0 mcg/mL FEU is equivalent to 0.5 mcg/mL of d-dimer.[19]

Thrombotic disease

Various kits have a 93 to 95% sensitivity (true positive rate). For hospitalized patients, one study found the specificity to be about 50% (related to false positive rate) in the diagnosis of thrombotic disease.[20]

In interpretation of the D-dimer, for patients over age 50, a value of (patient's age) × 10 μg/L may be abnormal.[23][24]

History

D-dimer was originally described in the 1970s and found its diagnostic application in the 1990s.[1][5]

References

External links