D-dimer

What is being tested?
When veins or arteries are injured, blood starts to leak from the vessel. Normally this triggers a series of clotting reactions in the blood involving the clotting factors in sequence. This process, commonly known as the coagulation “cascade”, culminates in the formation of a stable clot at the site of the injury, which stops the bleeding. The clotting process ends with the formation of a fibrous mesh, as thrombin converts fibrinogen into soluble fibrin. Through the action of factor XIII, the soluble fibrin is stabilised and made insoluble by cross-links between adjacent fibres, forming a stable mesh (the clot) that traps platelets and other blood cells.

Once the clot (thrombus) has formed at the site of the injury, a protein called plasmin breaks it down, removing it completely once it has done its job of stopping the bleeding. The fragments produced when the clot breaks down are called fibrin degradation products (FDPs). One of the degradation products of stabilised fibrin is D-dimer, which consists of fibrin molecules containing two cross-linked D units. The concentration of D-dimer in the blood is usually very low in healthy people, as it is normally produced only when an existing clot (thrombus) breaks down. A raised D-dimer concentration therefore reflects excessive activity of the clotting system.

How is it used?
D-dimer is requested, sometimes with other imaging and laboratory tests, to help diagnose or monitor hypercoagulable conditions or diseases, i.e. conditions characterised by an abnormal or excessive tendency of the blood to form clots (thrombi). The most common hypercoagulable condition is deep vein thrombosis (DVT), in which clots form in the deep veins of the body, especially in the legs. In this situation the clots can grow considerably, blocking blood flow in the veins and damaging the tissues, which shows up as a series of clinical signs or symptoms, including swelling of the affected area (limb), pain and redness of the skin. A fragment of the clot can also break off, forming an embolus that travels in the blood through the body’s vessels. The embolus often lodges in the vessels of the lung (pulmonary arteries or distal arteries of the lung), where it can cause a serious condition called pulmonary embolism. Deep vein thrombosis and pulmonary embolism are therefore two different clinical manifestations of the same disease process, called venous thromboembolism.

Although most clots and emboli originate in the veins, arteries can sometimes be affected too. Thrombosis or, less often, emboli lodging in arteries that carry oxygen and other nutrients to vital organs such as the brain, heart and kidneys can cause infarction, irreversible damage and dysfunction of the organ involved. D-dimer is usually requested to check that its blood concentration is not too high, in order to rule out conditions characterised by excessive or abnormal clot formation; it is therefore used mainly to rule out DVT or PE.

When is it requested?
D-dimer may be requested, together with other tests, to help diagnose suspected disseminated intravascular coagulation (DIC). DIC is a complex secondary clotting disorder that can complicate some conditions, including septicaemia, surgery, liver disease, complications of pregnancy (eclampsia, foetal death, placental abruption), cancer and venomous snake bites. DIC is characterised by abnormal, excessive activation of clotting, which leads to widespread clots in the blood vessels. The excessive clot formation is progressively accompanied by consumption of clotting factors and platelets, putting the patient at risk of bleeding. The most effective treatment for DIC is to remove the underlying cause; however, supportive treatment can be used until the responsible condition has been identified and removed. D-dimer can also help assess the progression of DIC and the effectiveness of treatment.

What does the test result mean?
A D-dimer result above the reference range indicates excess fibrin degradation products in the blood. It therefore reflects increased formation and breakdown of clots (thrombi) in the vessels, but gives no specific indication of their location or cause. High D-dimer values may reflect venous thromboembolism or DIC, but can also follow surgery, injury or infection. High concentrations are often found in pregnancy and in patients with severe liver disease, eclampsia and other obstetric problems, heart disease and cancer.

A normal D-dimer value usually rules out acute or chronic conditions characterised by increased formation and breakdown of clots in the vessels. There is broad agreement that a non-diagnostic D-dimer value is more valid and diagnostically efficient in patients at low risk of thrombotic disease. The test is most helpful for ruling out thrombosis as the cause of symptoms.

D-dimer is recommended as a supporting test, not a decisive one. Its result should therefore not be used as the only parameter for making a definite diagnosis. Both high and non-diagnostic concentrations require patient follow-up and may suggest requesting other, more specific tests.

Is there anything else I should know?
Antithrombotic and/or anticoagulant treatment can sometimes cause false negative D-dimer results, while fibrinolytic treatment can cause considerable rises in its concentration. Many methods are now available for measuring D-dimer in blood and plasma. Most methods that give quantitative results are used in hospitals, while rapid qualitative or semi-quantitative methods are available for use at the bedside, including outside hospital.

D-dimer can rise in some normal situations, such as pregnancy or old age. Occasionally false positives can be seen with some laboratory techniques when rheumatoid factors are present, especially in patients with rheumatoid arthritis. The test can be affected by samples from patients who have not fasted or that contain high triglycerides, and by incorrect or unsuitable blood collection (especially haemolysed samples).