The fibrin is a threadlike protein present in blood in its precursor form, fibrinogen, readily polymerizable to form fibrin filaments. These filaments form a fine mesh network capable of retaining blood cells during the formation of a clot.
Fibrinogen is part of the so-called plasma proteins, along with albumin and globulins. It is a fibrous protein that is transformed into fibrin in the presence of the enzyme thrombin.
Fibrin is currently used in regenerative medicine, together with other blood protein elements, such as growth factor, to promote tissue regeneration.
In the composition of fibrinogen, three globular domains are involved, two D, at the ends, and one E, in the center. Basically, it is made up of three polypeptide chains, with a total length of 46 nm and that wind up to form an alpha helix.
Due to the action of the thrombin enzyme, fibrinogen loses fibrinopeotides A and B, which are terminal and responsible for repelling other fibrinogen molecules. Thus a fibrin monomer is formed.
Fibrin monomers polymerize to form a polymer called a fibrin filament. This filament is stabilized thanks to the action of a factor called FXIIIa, forming an insoluble polymer.
The function of fibrin is to act as a binder in charge of forming a mesh around the platelet plug, forming a fibrin clot.
It is also responsible for keeping the scab attached to the lesion until the formation of new epithelial tissue.
Numerous substances are involved in the formation of the blood clot that interact in a complex and sequential way called the coagulation cascade. A simplified explanation of this process is as follows:
An inactive complex of two combined substances circulates freely in the blood: prothrombin and antiprothrombin. When injury occurs, damaged tissue cells and platelets in contact with the injury release a substance called thromboplastin.
Thromboplastin displaces prothrombin from the junction they form with antiprothrombin, thereby freeing prothrombin. This, in the presence of calcium ions from the blood, is transformed into a more active molecule called thrombin.
Thrombin acts as an organic catalyst on one of the soluble plasma proteins, fibrinogen. This is transformed into fibrin, which is insoluble, polymerizes into long filaments and then precipitates. Fibrin filaments form a network or mesh that traps platelets and blood cells, partially blocking blood loss.
Platelets trapped in the fibrin network bind to it and in a short time begin to contract. Due to this, the clot also contracts, releasing the excess liquids within the fibrin network; this is the exudate seen in healing wounds.
When the clot contracts, the edges of the wound tend to come together. When the clot is in contact with air, it causes the clot to dry out and to form what is known as a scab. The fibrinogen will keep this scab attached to the wound for the duration of healing.
A more recent hypothesis of blood clot formation is called the cellular model of coagulation. According to this model, the process is carried out in three phases, one for initiation, another for amplification and one for propagation.
While it is true that fibrin is essential for hemostasis, excessive or deficient production of this molecule can cause adverse effects in the body. Excess fibrin production can lead to thrombosis. At the other extreme, poor fibrin production can lead to bleeding.
Fibrinogen, the precursor of fibrin, is found in normal concentrations of 200-400 mg / dl; in women, the concentration is slightly higher than in men. Kidney and / or liver failure and other liver damage, as well as some infections can raise fibrinogen levels in the blood.
The concentrations of this plasma protein can also be elevated by diseases such as lupus erythematosus, leprosy, leukemia, diabetes, or by factors such as obesity, smoking, stress, among others.
In contrast, very low fibrinogen levels cause, as already noted, the propensity to bleed, and can also be due to multiple factors, including bacterial infections, burns, and cancer.
Afibrinogenesis is a disease that can be congenital or acquired, characterized by the absence or very low concentration of fibrinogen in the blood. Because of this, the sufferer is unable to form blood clots in wounds.
It can also be due to inadequate release of thromboplastin into the bloodstream, causing fibrinogen to transform into fibrin without forming thrombi, decreasing the availability of fibrinogen in the blood.
Dysibrinogenesis, on the other hand, is another disease caused, in this case, by a malfunction of fibrinogen. It is a genetic disease and those who suffer from it may not show clinical evidence or may have a tendency to bleed, and / or suffer from thrombosis.
Other fibrin- or fibrinogen-related diseases include hypofibrinogenemia, low levels of fibrinogen in the blood, and hypodysfibrinogenemia, low and dysfunctional fibrinogen levels.
Regenerative medicine is a branch of alternative medicine that uses novel methods to treat different types of injuries that are difficult to treat with traditional medicine. Protein elements from the blood or blood products have allowed promising advances in this type of treatment.
One of these blood products is, precisely, fibrin. This substance is used in the form of fibrin patches for the repair of skin lesions. It is generally used with platelet rich plasma (PRP).
These substances are extracted from autologous blood (from the same patient), which reduces the risk of transmitting diseases such as hepatitis or HIV.
One of the first areas to apply this type of therapy is dentistry, where these treatments have shown their ability to enhance the reduction of edema and postoperative pain, as well as to decrease the time required for healing.
They have also been used with encouraging or successful results in cases of maxillary and mandibular osteonecrosis and rhytidectomy. Tests are currently being carried out in other areas such as otorhinolaryngology, sports medicine, orthopedics and ophthalmology, among others.
In veterinary medicine they have been used successfully for fractures and skin wounds in racehorses.
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