As one of the 12 factors responsible for blood clotting, fibrinogen is essential for the body’s healing processes that we often take for granted. Read on to understand how fibrinogen functions in the body, why doctors test its levels, and what the normal range of fibrinogen is.
What is Fibrinogen?
Fibrinogen is a protein produced in the liver that is essential for a variety of processes, including blood clot formation, wound healing, inflammation, and blood vessel growth [1, 2].
It circulates throughout the bloodstream in concentrations of 2 g/L to 4 g/L, by far the highest concentration of any blood clotting factor. Fibrinogen breaks down after about 6 days in the bloodstream .
Fibrinogen is a positive acute phase protein, which means that its production is increased during injury, infection, and inflammation. This is mainly mediated by cytokines, such as IL-6 [3, 4, 5, 6].
1) Helps Blood Clotting
Blood clots are extremely important to our health because they stop excessive blood loss and initiate wound healing .
In the process of coagulation (clotting), protein strands and cell fragments (platelets) combine together to form a hardened clot. This newly formed clot plugs the site of the wound, preventing further bleeding while the blood vessel continues to bend and stretch around the site .
Blood clot formation occurs through a series of steps:
- During injury, fibrinogen is cut by the enzyme thrombin into fibrin strands .
- Next, enzyme factor XIII (activated by thrombin) cross-links the fibrin strands to create a net that, along with platelets, forms a blood clot .
- The fibrin strands also bind to thrombin to prevent it from cutting up more fibrinogen, thereby inhibiting continuous clot formation .
- Fibrinogen further contributes to clot formation by binding to receptors on the surface of platelets and bridging them together [9, 10].
2) Regulates the Breakdown of Blood Clots
Fibrinogen and its successor fibrin both affect the breakdown of clots (fibrinolysis) .
While fibrin activates plasmin (the enzyme that degrades clots), fibrinogen inhibits it. These opposing actions ensure that clots are broken down only after they are no longer needed .
This activity is significant because clots become detrimental when they block blood vessels, leading to heart attack and stroke .
3) Is Involved in Immune Defense and Healing
Fibrinogen binds to and activates specific white blood cells (U937, THP-1, Mac-1) in mice and in the lab, indicating that it plays a role in the immune response to infection or injury [14, 15, 16, 17].
In a gene association study of 631 sepsis patients, genetic mutations that resulted in increased blood fibrinogen levels were correlated with faster recovery and lower mortality .
Similarly, a study in mice with acetaminophen-induced liver damage found that fibrinogen enhanced liver repair by activating white blood cells .
Common Clotting Tests
These popular tests measure how long it takes blood to clot. Abnormally long times indicate a problem in clot formation, such as low levels of functional fibrinogen .
However, these tests measure a number of different protein interactions, so their results do not necessarily correlate with fibrinogen levels, nor are they sensitive to mild fibrinogen deficiency or dysfunction .
- Prothrombin Time (PT) measures the time it takes blood to clot after stimulating it with proteins that are released by damaged cells .
- A normal range for the PT is usually 10 to 14 seconds .
- Partial Thromboplastin Time (PTT) measures the time it takes blood to clot after adding a protein called factor XII, which stimulates the internal clotting pathway .
- A normal range for the PTT is around 25 to 35 seconds .
Fibrinogen-Specific Clotting Tests
- Thrombin Time (TT) measures the time it takes fibrinogen to be converted into fibrin by adding thrombin. It is sensitive to mild fibrinogen deficiency and dysfunction but is affected by other factors that inhibit thrombin, such as medication .
- A normal range for the TT is usually 12 to 14 seconds, with longer times indicating a deficiency in properly functioning fibrinogen .
- Reptilase Time (RT) also measures the conversion of fibrinogen to fibrin but using snake venom instead of thrombin. It is therefore as sensitive as the thrombin time test and not affected by medication .
- A normal range for the RT is around 18 to 22 seconds with longer times indicating functional fibrinogen deficiency .
Fibrinogen Level Tests
A Fibrinogen Activity test measures the conversion of fibrinogen into fibrin. It is measured by the two methods described above and converted into fibrinogen concentration in the blood (mg/dL) .
The Fibrinogen Antigen Test (or Immunological Fibrinogen Assay) measures how much fibrinogen is present in the blood by the presence of fibrinogen antibodies .
Fibrinogen blood levels vary in the general population and range from 175 – 425 mg/dL, with average levels varying by geographical region .
The normal level may vary between labs. For example, some labs have 150 to 500 mg/dL as the normal range.
Your doctor will interpret your fibrinogen test, taking into account your symptoms, medical history, and other test results.
Genes and Fibrinogen
People with dysfibrinogenemia have normal levels of fibrinogen but structural abnormalities that do not allow the molecule to function properly .
Approximately 55% of people with this disorder are without symptoms, 25% suffer from excessive bleeding, and the remaining 20% have excessive clotting .
Other symptoms include delayed wound healing, arterial blood clots, pregnancy complications, and skin necrosis (tissue death) [26, 27].
Congenital dysfibrinogenemia is typically autosomally dominant, meaning that only one parent needs to have the disorder for their child to inherit the disorder. Afflicted individuals are typically diagnosed as adults, possibly after they have passed it on to their children [28, 25].
Because of this and the large percentage of asymptomatic carriers, scientists suggest it may affect up to one in 100 people .
Though dysfibrinogenemia is typically caused by inherited mutations, there have been rare cases of acquired dysfibrinogenemia [30, 31].
Hereditary Renal Amyloidosis
Hereditary renal amyloidosis describes the harmful build-up of proteins (amyloid fibrils) in the kidneys, which can lead to kidney failure and death [32, 33].
Hereditary renal amyloidosis is caused by a variety of inherited mutations (including a mutation in fibrinogen’s Aα amino acid chain) [34, 35, 32].
SNPs in Fibrinogen Genes
Fibrinogen levels are influenced by your genes. If you’re not interested in genetics, skip this part.
Three different genes encoding fibrinogen (FGA, FGB, and FGG) are used to produce the three chains that compose fibrinogen, Aα, Bβ, and γ .
Common alternative expressions of the FGA and FGG genes result in the functional fibrinogen subtypes AαE and γ’, respectively .
rs2070006 (T>C) has been associated with high blood fibrinogen levels .
rs2070011 (T>C) has been associated with high blood fibrinogen levels, possibly by increasing interleukin-6 production of the fibrinogen gene [37, 38].
rs146387238 (C>A / C>G) has been linked to afibrinogenemia (very low blood fibrinogen levels) .
rs6050 (G>A) (major allele) is associated with high blood fibrinogen levels [40, 41].
rs1800787 (C>T) is associated with low fibrinogen, slow initiation of the coagulation cascade, and possibly childhood pneumonia [38, 42].
rs1800790 (G>A) (minor allele) is associated with high fibrinogen, as well as reduced inflammatory response and increased risk of heart disease, likely because this sequence affects the production of the entire FGB gene [40, 43, 44, 37].
rs1800791 (G>A) is associated with high blood fibrinogen levels [45, 38].
rs2227399 (G>T) is associated with high blood fibrinogen levels .
rs4220 (G>A) is associated with high blood fibrinogen levels and clots resistant to degradation [37, 38].
rs4463047 (T>C) is associated with low blood fibrinogen levels [46, 47].
rs7439150 (G>A) influences fibrinogen concentration [45, 48].
rs1049636 (T>C) is associated with higher blood fibrinogen levels, likely by increasing the production of the fibrinogen gene by IL-6 [45, 38].
rs148685782 (G>C) is associated with low blood fibrinogen levels and hypofibrinogenemia [47, 49].
rs2066865 (C>T) (minor allele) is associated with an increased risk of harmful blood clots .
So far, we have only been able to identify 3% of the estimated 34 to 46% of the variation in blood fibrinogen levels between individuals that are controlled by genes [37, 51, 52].
Fibrinogen is a blood-clotting protein produced in the liver in response to injury, infection, and inflammation. Your body requires it to close and heal wounds and grow new blood vessels. A balance of fibrinogen and its breakdown product fibrin helps you get rid of unneeded blood clots that block blood vessels. Fibrinogen may also enhance tissue regeneration by increasing your immune defense. Doctors usually assess fibrinogen levels indirectly by measuring your clotting time (Prothrombin Time or Partial Thromboplastin Time). A longer clotting time points to low fibrinogen levels. Thrombin time and reptilase time are more sensitive clotting tests that can detect mild fibrinogen deficiency. More precise tests like the Functional Fibrinogen Assay and Fibrinogen Antigen Test measure your actual fibrinogen levels.