What are D-dimers and when are they measured?

D-dimers are degradation products of a fibre protein called fibrin. When fibrin and blood platelets layer on top of each other, they form a plug. This takes place within the blood vessel in healthy blood clotting (wound healing); it also happens during the pathological formation of a blood clot (thrombus). A thrombus can either obstruct a blood vessel (thrombosis) or it can be swept along in the bloodstream to another location and completely block a vessel (embolism).

Once injuries heal, the body produces the enzyme plasmin, which breaks down the clot into small fragments that can then be removed. These fragments are referred to as fibrin degradation products, and D-dimer is one of these fibrin degradation products.

Small quantities of D-dimer can be found in the plasma of healthy individuals due to continuous physiological turnover (fibrin formation and lysis) of 2-3% of plasma fibrinogen.

In blood clotting disorders, clots may also form when no injury is present and/or when clots are not broken down quickly enough.

Measuring plasma D-dimers is generally the first test performed on patients with a suspected acute pulmonary embolism (PE) or deep vein thrombosis (DVT).

In addition to DVT and pulmonary embolism, there are still other factors that are associated with positive D-dimer results. The medical literature describes a number of these, such as advanced age, rheumatoid arthritis, pregnancy, coronary heart disease, recent surgical procedures, cancer, liver disorders, trauma and infections (D-dimer tests are almost always positive if the CRP value is 6.5 mg/dl or higher).

A D-dimer test does not indicate the type of clotting disorder present or where the clot is located in the body.

D-dimer tests are non-invasive and fast, making it unsurprising that the availability of these tests increases the number of patients that can be examined for a potential DVT or pulmonary embolism.

Its low specificity, however, does limit the benefit of a D-dimer test. Specificity generally lies between 40% and 60%, which leads to a high rate of false-positive results. If the pretest likelihood of a DVT is low, a sensitive test can be performed on patients with normal D-dimer levels to rule out a DVT with certainty.

A positive test result, however, is non-specific, as levels may be elevated for other reasons as well, requiring additional tests.

If the pretest likelihood of a DVT is moderate or high, a D-dimer determination can be performed at the same time as duplex sonography. A positive sonography result confirms the diagnosis regardless of the patient’s D-dimer levels.

If sonography does not indicate the presence of a DVT, a normal D-dimer level can help to rule out a DVT. For patients with elevated D-dimer levels, sonography should be repeated after a few days, or additional imaging methods should be brought to bear.

Even though multiple D-dimer tests are on the market, there is no gold standard for comparing the results – in other words, there is no “normal” D-dimer value.

Physicians must therefore be familiar with the test used and with the manufacturer’s recommended parameters.

The tests may be quantitative, with results given in numerical units such as nanogrammes per millilitre. They may also be non-quantitative, with results given as positive or negative values.

Quantitative tests indicate recommended threshold values for positive results and use units such as nanogrammes per millilitre, milligrammes per litre of fibrinogen equivalent units (FEUs) or D-dimer units. Units are not interchangeable between test products, as each product has its own parameters.