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The specific degradation of fibrin (ie, fibrinolysis) is the reactive mechanism responding to the formation of fibrin. Plasmin is the fibrinolytic enzyme derived from inactive plasminogen. Plasminogen is converted into plasmin by plasminogen activators. The main plasminogen activators are tissue plasminogen activator (tPA) and pro-urokinase, which is activated into urokinase (UK) by, among others, the contact system of coagulation. In the bloodstream, plasmin is rapidly and specifically neutralized by alpha-2-antiplasmin, thereby restricting its fibrinogenolytic activity and localizes the fibrinolysis on the fibrin clot. On the fibrin clot, plasmin degrades fibrin into various products (ie, D-dimers). Antibodies specific for these products, which do not recognize fibrinogen, have been developed. The presence of these various fibrin degradation products, among which D-dimer is the terminal product, is the proof that the fibrinolytic system is in action in response to coagulation activation. Elevated D-dimer levels are found in association with disseminated intravascular coagulation (DIC), pulmonary embolism (PE), deep vein thrombosis (DVT), trauma, and bleeding. D-dimer may also be increased in association with pregnancy, liver disease, malignancy, inflammation, or a chronic hypercoagulable state.

About

D-dimer is one of the protein fragments produced when a blood clot gets dissolved in the body. It is normally undetectable or detectable at a very low level unless the body is forming and breaking down blood clots. Then, its level in the blood can significantly rise. This test detects D-dimer in the blood.


When a blood vessel or tissue is injured and begins to bleed, a process called haemostasis 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 crosslinks 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 are 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 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 clot is present. It 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 DVT affect more than 300,000 people in the U.S. each year.


While 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). 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 DIC.

Preparation

The D-dimer blood involves taking a simple blood sample and sending it to the lab for testing. No preparation is needed before the test.

Indications

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, such as:

  • Leg pain or tenderness, usually in one leg
  • Leg swelling, oedema
  • Discolouration of the leg


It may be ordered when someone has symptoms of pulmonary embolism such as:

  • Sudden shortness of breath, laboured 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 PT, PTT, fibrinogen, and platelet count, to help diagnose the condition. D-dimer may also be ordered at intervals when someone is undergoing treatment for DIC to help monitor its progress.

Interpretation

A normal or "negative" D-dimer result (D-dimer level is below a predetermined cut-off threshold) 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 test is used to help rule out clotting as the cause of symptoms.


A positive D-dimer result may indicate the presence of an abnormally high level of fibrin degradation products. It indicates that there may be a significant blood clot (thrombus) formation and breakdown in the body, but it does not tell the location or cause. For example, it may be due to venous thromboembolism (VTE) or disseminated intravascular coagulation (DIC). Typically, the D-dimer level is very elevated in 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 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 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 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 PT, PTT, fibrinogen, and platelet count to help diagnose her condition. If the woman has 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. It 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.

Disclaimer

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario. Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider of the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

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