What is D-dimer

D-dimer is one of the protein fragments produced when a blood clot gets dissolved in the body (see Figure 1B below – Fibrinolytic Pathway). D-dimer is normally undetectable or detectable at a very low level unless your body is forming and breaking down blood clots. Then, D-dimer level in your blood can significantly rise.

When a blood vessel or tissue is injured and begins to bleed, a process called hemostasis is initiated by the body to create a blood clot to limit and eventually stop the bleeding. This process produces threads of a protein called fibrin, which crosslink together to form a fibrin net. That net, together with platelets, helps hold the forming blood clot in place at the site of the injury until it heals.

Once the area has had time to heal and the clot is no longer needed, the body uses an enzyme called plasmin to break the clot (thrombus) into small pieces so that it can be removed. The fragments of the disintegrating fibrin in the clot are called fibrin degradation products (FDP), which consist of variously sized pieces of crosslinked fibrin. One of the final fibrin degradation products produced is D-dimer, which can be measured in a blood sample when present. The level of D-dimer in the blood can significantly rise when there is significant formation and breakdown of fibrin clots in the body.

For a person who is at low or intermediate risk for blood clotting (thrombosis) and/or thrombotic embolism, the strength of the D-dimer test is that it can be used in a hospital emergency room setting to determine the likelihood of a blood clot’s presence. A negative D-dimer test (D-dimer level is below a predetermined cut-off threshold) indicates that it is highly unlikely that a thrombus is present. However, a positive D-dimer test cannot predict whether or not a blood clot is present. However, a positive D-dimer test does not tell your doctor where the blood clot was or what caused it. Other health problems can also cause the D-dimer level to go up (see High D-dimer levels below for causes). Therefore, the D-dimer test is not the only test used to diagnose a disease or condition. D-dimer test is usually used with other blood tests and imaging scans. Positive D-dimer test indicates that further diagnostic procedures are required (e.g., ultrasound, CT angiography).

There are several factors and conditions associated with inappropriate blood clot formation. One of the most common is deep vein thrombosis (DVT), which involves clot formation in veins deep within the body, most frequently in the lower legs. These clots may grow very large and block blood flow in the legs, causing swelling, pain, and tissue damage. It is possible for a piece of the clot to break off and travel to other parts of the body. This “embolus” can lodge in the lungs, causing a pulmonary embolus or embolism (PE). Pulmonary embolisms from deep vein thrombosis (DVT) affect more than 300,000 people in the U.S. each year.

While blood clots most commonly form in the veins of the legs, they may also form in other areas as well. Measurements of D-dimer can be used to help detect clots in any of these sites. For example, clots in coronary arteries are the cause of myocardial infarction (heart attacks). Clots may form on the lining of the heart or its valves, particularly when the heart is beating irregularly (atrial fibrillation) or when the valves are damaged. Clots can also form in large arteries as a result of narrowing and damage from atherosclerosis. Pieces of such clots may break off and cause an embolus that blocks an artery in another organ, such as the brain (causing a stroke) or the kidneys.

Measurements of D-dimer may also be ordered, along with other tests, to help diagnose disseminated intravascular coagulation (DIC). Disseminated intravascular coagulopathy (DIC) is a condition in which clotting factors are activated and then used up throughout the body. This creates numerous tiny blood clots and at the same time leaves the affected person vulnerable to excessive bleeding. It is a complex, sometimes life-threatening condition that can arise from a variety of situations, including some surgical procedures, sepsis, poisonous snake bites, liver disease, and after childbirth. Steps are taken to support the affected person while the underlying condition resolves. The D-dimer level will typically be very elevated in disseminated intravascular coagulopathy (DIC).

Figure 1. Overview of blood coagulation

D-dimer test

D-dimer test measures the amount of D-dimer, which is normally undetectable, in your blood. A D-dimer test is a blood test usually used to help check for or monitor blood clotting problems. A positive test means the D-dimer level in your body is higher than normal and suggests you might have blood clots.

Blood clots form whenever a blood vessel is damaged, whether that’s by an injury or by atherosclerosis, or when blood flow is restricted, such as by a vessel being compressed for a long time. When you have an injury, your body creates a blot clot to stop blood from leaking out of your blood vessels. D-dimer is a type of protein your body produces to break down the blood clot.

D-dimer testing is not well studied in children.

How is D-dimer test used?

D-dimer tests are used to help rule out the presence of an inappropriate blood clot (thrombus). Your doctor might ask you to have D-dimer test if he or she suspects you have blood clotting problems or wants to rule them out.

Some of the conditions that the D-dimer test is used to help rule out include:

• Deep vein thrombosis (DVT) — clot formation in the veins, usually in the legs
• Pulmonary embolism (PE) — a blockage in an artery in the lung
• Stroke
• Disseminated intravascular coagulation (DIC) — a condition that prevents your blood clotting normally.
• Blood coagulation caused by venom of certain species of snake, such as brown snake.

D-dimer test may be used to determine if further testing is necessary to help diagnose diseases and conditions that cause hypercoagulability, a tendency to clot inappropriately.

A D-dimer level may be used to help diagnose disseminated intravascular coagulation (DIC) and to monitor the effectiveness of disseminated intravascular coagulation (DIC) treatment.

When is D-dimer test ordered?

D-dimer testing is often ordered when someone goes to the emergency room with symptoms of a serious condition (e.g., chest pain and difficulty in breathing).

A D-dimer test may be ordered when someone has symptoms of deep vein thrombosis (DVT), such as:

• Leg pain or tenderness, usually in one leg
• Leg swelling, edema
• Discoloration of the leg

D-dimer test may be ordered when someone has symptoms of pulmonary embolism (PE) such as:

• Sudden shortness of breath, labored breathing
• Coughing, hemoptysis (blood present in sputum)
• Lung-related chest pain
• Rapid heart rate

D-dimer is especially useful when a healthcare practitioner thinks that something other than deep vein thrombosis or pulmonary embolism is causing the symptoms. It is a quick, non-invasive way to help rule out abnormal or excess clotting as the underlying cause. However, it should not be used when the probability of pulmonary embolism is high based on clinical assessment.

When a person has symptoms of disseminated intravascular coagulation (DIC), such as bleeding gums, nausea, vomiting, severe muscle and abdominal pain, seizures, and decreased urine output, a D-dimer test may be ordered, along with a prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, and platelet count, to help diagnose the condition. D-dimer may also be ordered at intervals when someone is undergoing treatment for disseminated intravascular coagulation (DIC) to help monitor its progress.

D-dimer levels

There are several different methods of testing for D-dimer. The currently available D-dimer tests that yield quantitative results are typically done in a hospital lab. Since different tests are used in different units, the results of one cannot be extrapolated to another.

• Less than or =250 ng/ml D-Dimer Units (DDU)
• Less than or =500 ng/mL (< or =0.50 mcg/mL) Fibrinogen Equivalent Units (FEU)

D-dimer values < or =250 ng/mL D-Dimer Units (DDU) (< or =0.50 mcg/mL Fibrinogen Equivalent Units [FEU]) are normal. Within the reportable normal range (110-250 ng/mL DDU; 0.22-0.50 mcg/mL FEU), measured values may reflect the activation state of the procoagulant and fibrinolytic systems, but the clinical utility of such quantitation is not established.

A normal D-dimer result (< or =250 ng/mL D-Dimer Units (DDU); < or =0.50 mcg/mL Fibrinogen Equivalent Units [FEU]) has a negative predictive value of approximately 95% for the exclusion of acute pulmonary embolism (PE) or deep vein thrombosis (DVT) when there is low or moderate pretest pulmonary embolism or deep vein thrombosis probability. In other words, a normal or “negative” D-dimer result (< or =250 ng/mL D-Dimer Units (DDU); < or =0.50 mcg/mL Fibrinogen Equivalent Units [FEU]) means that it is most likely that the person tested does not have an acute condition or disease causing abnormal clot formation and breakdown. Most health practitioners agree that a negative D-dimer is most valid and useful when the test is done for people who are considered to be at low to moderate risk for thrombosis. The D-dimer test is used to help rule out clotting as the cause of symptoms.

D-dimer concentrations increase with age and, thus, the specificity for deep vein thrombosis (DVT) and pulmonary embolism (PE) exclusion decreases with age. For deep vein thrombosis (DVT) or pulmonary embolism (PE) exclusion, in addition to clinical pretest probability, age-adjusted D-dimer cutoffs are suggested for patients more than 50 years of age.

Recent evidence suggests using clinical pretest probability and age-adjusted cutoffs to improve the performance of D-dimer testing in patients greater than 50 years of age. In recent studies, when compared to a fixed D-dimer cutoff, age adjusted D-dimer cutoff values (calculated as follows: age [years] x 10 ng/mL) resulted in equivalent outcomes and no additional false negative findings ¹⁾.

Lipemia can interfere with this assay, occasionally causing an under-estimation of the D-dimer level. Therefore, results from lipemic specimens should be interpreted with caution.

High D-dimer levels

Elevated D-dimer values are abnormal but do not indicate a specific disease state. A higher than normal D-dimer level might mean you have had a significant blood clot. A positive D-dimer result may indicate the presence of an abnormally high level of fibrin degradation products. Elevated D-dimer value indicates that there may be significant blood clot (thrombus) formation and breakdown in the body, but it does not tell the location of the clot or what caused it. For example, it may be due to a venous thromboembolism (VTE) or disseminated intravascular coagulation (DIC). Typically, the D-dimer level is very elevated in disseminated intravascular coagulation (DIC).

However, an elevated D-dimer does not always indicate the presence of a clot because a number of other factors can cause an increased level. Elevated D-dimer levels may be seen in conditions in which fibrin is formed and then broken down, such as recent surgery, trauma, infection, heart attack, and some cancers or conditions in which fibrin is not cleared normally, such as liver disease. Therefore, D-dimer is typically not used to rule out venous thromboembolism (VTE) in hospitalized patients (inpatient setting).

Fibrin is also formed and broken down during pregnancy, so that may result in an elevated D-dimer level. However, if disseminated intravascular coagulation (DIC) is suspected in a woman who is pregnant or is in the immediate postpartum period, then the D-dimer test may be used, along with a prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, and platelet count to help diagnose her condition. If the woman has disseminated intravascular coagulation (DIC), her D-dimer level will be very elevated.

D-dimer is recommended as an adjunct test. Since D-dimer is a sensitive test but has a poor specificity, it should only be used to rule out deep vein thrombosis (DVT), not to confirm a diagnosis. D-dimer test should not be used for pulmonary embolism when the clinical probability of that condition is high. Both increased and normal D-dimer levels may require follow-up and can lead to further diagnostic testing. People with positive D-dimer tests and those with moderate to high risk for DVT require further study with diagnostic imaging (e.g., CT angiography).

When used to monitor DIC treatment, decreasing levels indicate that treatment is effective while increasing levels may indicate that treatment is not working.

D-dimer values may be elevated as a result of:

• Clinical or subclinical disseminated intravascular coagulopathy (DIC) or intravascular coagulation and fibrinolysis.
• Other conditions associated with increased activation of the procoagulant and fibrinolytic mechanisms such as:
  • Recent surgery,
  • Active or recent bleeding,
  • Hematomas,
  • Trauma,
  • Thromboembolism.
• D-dimer levels can be positive due to:
  • Pregnancy,
  • Liver disease,
  • Inflammation,
  • Cancer,
  • Hypercoagulable (procoagulant) states,
  • High lipid or triglyceride levels (lipidemia)
  • Heart disease
  • Being over 80 years old

Other health problems outlined above can also cause the D-dimer level to go up. This makes the D-dimer test mostly useful when it is negative, when many of the above causes can be ruled out.

Therefore, the D-dimer test is not the only test used to diagnose a disease or condition. It is usually used with other blood tests and imaging scans. And the degree of D-dimer increase does not definitely correlate with the clinical severity of associated disease states.

Common risk factors for inappropriate blood clotting

Some risk factors include:

• Major surgery or trauma
• Hospitalization or living in a nursing home
• Prolonged immobility—this can include long trips by plane, car, etc. or prolonged bed rest
• Use of birth control or hormone replacement therapy
• Broken bone, cast
• Pregnancy or recent childbirth
• Antiphospholipid syndrome
• Certain cancers
• Inherited clotting disorder such as factor V Leiden mutation
• History of prior venous thromboembolism (VTE)
• Obesity
• Smoking

If the D-dimer test is positive, then you might be sent for imaging. A normal D-dimer level usually indicates a clotting problem is unlikely.

The presence of rheumatoid factor (a protein seen in people with rheumatoid arthritis) at a level above 50 IU/mL may lead to an overestimation of the D-dimer level.

What other procedures might my healthcare practitioner order if my D-dimer is positive?

In an emergency room setting, if you are found to be at low to intermediate risk for thrombosis and/or venous thromboembolism and when you have a positive D-dimer test, your healthcare practitioner will likely order a non-invasive scanning procedure, such as a venous ultrasound, multi-detector helical computed axial tomography (CT), direct pulmonary angiography, or ventilation-perfusion (V/Q) scan.