D-Dimer, Quantitative

D-dimer is a product of fibrin clot digestion and therefore is an indicator of recent or current clot formation and lysis. It is the most frequently used marker of coagulation and fibrinolysis.¹

D-dimer concentrations are increased in all conditions associated with enhanced fibrin formation and fibrinolysis, such as the following²:

• Venous thromboembolism (VTE); eg, deep vein thrombosis and pulmonary embolism
• Myocardial infarction and stroke
• Disseminated intravascular coagulation
• Malignancy
• Trauma or surgery within the previous 4 weeks
• Liver cirrhosis or disease
• Pregnancy
• Advanced age (>60 years)
• Sickle cell disease
• Large hematoma
• Fibrinolytic therapy within the previous 7 days
• Sepsis, severe infections, pneumonia
• Other atherosclerotic vascular disease

The utility of the assay lies in its negative predictive value, since a high D-dimer value is a non-specific finding. A negative result (D-dimer concentration below the cutoff) can be used to assist in the exclusion of VTE in certain patient populations.

D-dimer testing is often utilized in a diagnostic algorithm that combines clinical decision rules and imaging studies. If the clinical decision rule categorizes a patient as low risk or unlikely to have VTE and the patient has a negative D-dimer test (using a sensitive assay), then the diagnosis is excluded.^3,4 Examples of clinical decision rules can be found at http://asheducationbook.hematologylibrary.org/content/2013/1/457/T1.large.jpg.

Quest Diagnostics reports D-dimer results in µg/mL (mcg/mL) fibrinogen equivalent units (FEU). Other laboratories report D-dimer results using a D-dimer unit (DDU).

An FEU reflects the quantity of fibrinogen that was initially present that leads to the observed D-dimer. The molecular weight of a D-dimer fragment is approximately one-half the molecular weight of the fibrinogen molecule. Therefore 1.0 µg/mL FEU is equivalent to 0.5 µg/mL DDU.

Laboratories variously express results as ng/mL, mcg/mL, µg/L, etc. When comparing results obtained from different laboratories it is important to note the type and magnitude of units in order to make accurate conclusions.¹

In contrast to most other laboratory assays, a reference interval is not reported with the D-dimer assay. As the utility of the assay lies in its ability to assist in VTE exclusion, only the cutoff value is reported.

The cut-off value is 0.5 µg/mL (mcg/mL) FEU. In patients with a low to moderate clinical risk assessment and a D-dimer result below the cutoff value, the likelihood of a thrombotic event is very low. However, a thromboembolic event should not be excluded solely on the basis of the D-dimer level.⁵

Age-adjusted D-dimer thresholds (rather than a fixed cut-off value) have been recommended by the Clinical Guidelines Committee of the American College of Physicians. For patients older than 50 years with suspected pulmonary embolism, the age-adjusted cutoff can be used to determine whether imaging is warranted; the following formula would be used: age x 0.01 µg/mL FEU. For example, the D-dimer threshold for a 57-year-old individual would be 57 x 0.01 µg/mL FEU, or 0.57 µg/mL FEU.⁶

Not yet.  Clinical prediction rules that incorporate D-dimer testing have been proposed for use in predicting recurrent VTE and justifying continued anticoagulation. However, these need further validation to determine their safety, as recurrent VTE risk also depends on clinical variables.^7-9