Fibrinogen

What is being analysed?
Fibrinogen is a clotting factor, a protein essential for clot formation. It is produced by the liver and released into the blood together with about 20 other clotting factors. Normally, when tissues or blood vessels are injured, a sequential (cascade) activation of the clotting factors is triggered. At the end of the coagulation cascade, soluble fibrinogen is converted into insoluble fibrin, which forms a dense mesh and is stabilised at the site of the injury by clotting factor XIII. The stabilised fibrin mesh, together with other cellular elements, especially platelets, forms a stable clot. The barrier created in this way prevents further blood from leaking out of the vessel and stays in place until the wound has fully healed.

Fibrinogen is one of the acute phase factors or proteins. This means that its concentration can rise rapidly in all inflammatory or traumatic conditions

How is it used?
When is it requested?
What does the test result mean?
Is there anything else I should know?

How is it used?
Fibrinogen is usually requested together with other laboratory tests. This test assesses the blood’s ability to clot. Fibrinogen can help with further investigation when the prothrombin time (PT) and/or activated partial thromboplastin time (APTT) are prolonged, in people with prolonged or unexplained bleeding episodes. The test may also be requested to help diagnose disseminated intravascular coagulation (DIC), together with PT, APTT, platelet count and D-dimer. Occasionally fibrinogen can help monitor the progression of some chronic diseases (for example liver disease) or the response to treatment in serious acquired conditions (for example DIC).

Fibrinogen is sometimes requested together with other markers, such as C-reactive protein (CRP), to better assess the risk of developing cardiovascular disease. There is no unanimous agreement on measuring fibrinogen for this purpose, both because its association with cardiovascular disease has not been definitively established and because there is no effective treatment to lower it. Nevertheless, some doctors believe that fibrinogen can provide additional information to justify treating more aggressively people who have other important risk factors that can be modified by treatment (for example total cholesterol, LDL and HDL cholesterol).

When is it requested?
Fibrinogen may be requested in patients with unexplained or prolonged bleeding or when the PT and/or APTT are prolonged. The test may also be requested when there are symptoms of DIC, or to monitor treatment of DIC.

Fibrinogen may also be requested together with other clotting factors when an inherited qualitative or quantitative deficiency is suspected, or to monitor over time the haemostatic function of a patient with an acquired bleeding disorder (for example uraemia).

In some circumstances fibrinogen may be requested together with other tests to assess the risk of developing cardiovascular disease.

What does the test result mean?
Fibrinogen levels reflect the body’s haemostatic capacity and activity. Low fibrinogen levels can reduce the ability to form a stable clot. Persistently low fibrinogen levels may be due to an inherited production defect, as in hereditary afibrinogenaemia, or to acquired conditions such as liver failure or malnutrition (hypofibrinogenaemia). An acute fall in fibrinogen is often due to increased consumption, as in disseminated intravascular coagulation (DIC) and, more rarely, in some advanced cancers. In these situations there is initially heavy consumption of clotting factors, with abnormal clot (thrombus) formation, followed by bleeding as levels progressively fall. In very rare cases (primary hyperfibrinolysis), the proteins of the fibrinolytic system, which normally break down the stabilised clot, can lower fibrinogen levels by breaking it down directly or by dissolving fibrin too quickly.

Even when there are qualitative fibrinogen abnormalities, some laboratory methods may give normal values, which usually reflect normal clotting. This is a very rare condition characterised by the production of abnormal fibrinogen molecules (dysfibrinogenaemia). It is generally due to a rare inherited mutation in the fibrinogen gene, which leads to the production of an abnormal protein. When there are clinical signs suggesting qualitative fibrinogen abnormalities, further tests (immunological fibrinogen measurement) are indicated to better characterise the nature of the defect.

Fibrinogen is an acute phase protein: this means that its concentration can rise considerably with inflammation or tissue damage. High fibrinogen concentrations are not a specific finding and give no information about the cause or location of the disease. Doctors often do not request fibrinogen in these situations, precisely because they expect to find raised levels. These increases are generally temporary and return to baseline once the condition has resolved. High levels may be found with:

• Acute infections
• Cancer in general
• Cardiovascular disease and heart attack
• Chronic DIC (in this case fibrinogen may be requested for monitoring)
• Inflammatory diseases (such as rheumatoid arthritis and glomerulonephritis)
• Stroke
• Injuries

Raised fibrinogen levels are associated with a slight to moderate increase in the risk of thrombosis in patients with cardiovascular disease. For this reason fibrinogen is often requested together with other cardiovascular risk markers.

Is there anything else I should know?
Recent blood transfusions can affect fibrinogen results. Some medicines can lower fibrinogen levels: anabolic steroids, androgens, streptokinase, urokinase and some antiepileptic medicines. Small increases in fibrinogen are sometimes seen during pregnancy, in smokers and in people taking oral contraceptives or oestrogens
Dysfibrinogenaemia is a rare clotting disorder caused by a mutation in the fibrinogen gene. This produces an abnormal fibrinogen molecule that is more resistant to breakdown once it has been converted into fibrin. Dysfibrinogenaemia can be associated with episodes of venous thromboembolism (deep vein thrombosis and pulmonary embolism). PT, APTT and thrombin time are useful screening tests for this condition, but specific blood tests are needed for a definite diagnosis. Patients with fibrinogen deficiency or dysfibrinogenaemia may sometimes have difficulty with wound healing

1. What can I do to lower my fibrinogen levels?
2. What is the difference between fibrinogen, D-dimer and fibrin degradation products?

1. What can I do to lower my fibrinogen levels?
If the raised fibrinogen is due to pregnancy or an acute inflammatory disease, it will resolve on its own. If high fibrinogen is due to an acquired disease, such as rheumatoid arthritis, there are no effective measures to change it. If the doctor thinks that high fibrinogen levels are responsible for an increased cardiovascular risk, it will be advisable to make lifestyle changes and act on other modifiable risk factors, for example by lowering total cholesterol and raising HDL cholesterol. There is also some evidence that a diet rich in omega-3 and omega-6 fatty acids (found in fish oil) can lower fibrinogen levels.

2. What is the difference between fibrinogen, D-dimer and fibrin degradation products (FDPs)?
The fibrinogen test measures soluble clotting factor I, before it is converted into insoluble fibrin and trapped in the fibrin mesh. D-dimer and fibrin degradation products (FDPs) help assess the activity of the fibrinolytic system, which breaks down clots when they are no longer needed so that they can be removed. The FDP test measures all the fragments of the dissolving clot, while the D-dimer test measures a group of breakdown fragments of cross-linked fibrin.