Fibrin glue (also called fibrin sealant) is a surgical formulation used to create a fibrin

clot A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...

for

hemostasis In biology, hemostasis or haemostasis is a process to prevent and stop bleeding, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. This involves coagulation, ...

, cartilage repair surgeries or

wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...

. It contains separately packaged human

fibrinogen Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood cl ...

and human

thrombin Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma- ...

Medical uses

This glue is used as a

supportive treatment Symptomatic treatment, supportive care, supportive therapy, or palliative treatment is any medical therapy of a disease that only affects its symptoms, not the underlying cause. It is usually aimed at reducing the signs and symptoms for the comfo ...

in surgery (such as liver surgery) for the improvement of

where standard surgical techniques are insufficient or impractical. It is also used for repairing

dura mater In neuroanatomy, dura mater is a thick membrane made of dense irregular connective tissue that surrounds the brain and spinal cord. It is the outermost of the three layers of membrane called the meninges that protect the central nervous system. ...

tears and bronchial

fistula A fistula (plural: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") in anatomy is an abnormal connection between two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other hollow or ...

s and for achieving hemostasis after

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

and liver trauma, in "no sutures" corneal transplantation,

pterygium Pterygium (plural ''pterygia'' or ''pterygiums'') refers to any wing-like triangular membrane occurring in the neck, eyes, knees, elbows, ankles or digits. The term comes from the Greek word ''pterygion'' meaning "wing". Types * Popliteal pter ...

excision with amniotic membrane or

conjunctiva The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epithelium ...

autograft Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person ('' auto-'' meaning "self" in Greek). The autologous tissue (also called autogenous, autogen ...

, and in eye trauma for corneal or conjunctival defects, as well as for

skin graft Skin grafting, a type of graft surgery, involves the transplantation of skin. The transplanted tissue is called a skin graft. Surgeons may use skin grafting to treat: * extensive wounding or trauma * burns * areas of extensive skin loss du ...

donor site wounds to reduce postoperative pain. It can also be used to treat

pilonidal sinus Pilonidal disease is a type of skin infection which typically occurs as a cyst Intergluteal cleft, between the cheeks of the buttocks and often at the upper end. Symptoms may include pain, swelling, and redness. There may also be drainage of flui ...

disease but it is of unclear benefit as of 2017, due to insufficient research.

Contraindications

The glue must not get into blood vessels, as this could lead to clotting in the form of

thromboembolism Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (t ...

or disseminated intravascular coagulation, or to

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the foll ...

(a severe allergic reaction).

Side effects

Possible adverse effects include

bleeding disorder Coagulopathy (also called a bleeding disorder) is a condition in which the blood's ability to coagulate (form clots) is impaired. This condition can cause a tendency toward prolonged or excessive bleeding (bleeding diathesis), which may occur spo ...

and allergic reactions such as flushing, stinging, generalised

urticaria Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-last ...

angioedema Angioedema is an area of swelling (edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which are ...

bronchospasm Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylatoxins. It causes di ...

, and anaphylaxis. Other adverse effects in studies occurred in roughly equal proportions in treatment and

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...

groups.

Interactions

As fibrin glue contains proteins, it may be denatured by

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...

, iodine and heavy metals. These substances are frequently found in

antiseptic An antiseptic (from Greek ἀντί ''anti'', "against" and σηπτικός ''sēptikos'', "putrefactive") is an antimicrobial substance or compound that is applied to living tissue/skin to reduce the possibility of infection, sepsis, or putre ...

solutions.

Pharmacology

Mechanism of action

Thrombin Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma- ...

is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

that splits

into fibrin monomers in 10 to 60 seconds, which aggregate to form a three-dimensional gel-like structure. Thrombin also activates

factor XIII Factor XIII or fibrin stabilizing factor is a zymogen found in blood of humans and some other animals. It is activated by thrombin to factor XIIIa. Factor XIIIa is an enzyme of the blood coagulation system that crosslinks fibrin. Deficiency of X ...

from the human body to factor XIIIa, which then cross-links the fibrin monomers to form a stable clot. Both these processes need

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

to work. As the wound heals, the clot is slowly degraded by the enzyme

plasmin Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encode ...

Pharmacokinetics

In rabbit studies, only 1 to 2% of the applied thrombin dose reached the bloodstream. It reached highest

blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intr ...

concentrations after 6 to 8 hours.

Chemistry

Composition

Fibrin glue comes in two vials, respectively containing * fibrinogen: lyophilised pooled human concentrate and * thrombin: This used to be of

bovine Bovines (subfamily Bovinae) comprise a diverse group of 10 genera of medium to large-sized ungulates, including cattle, bison, African buffalo, water buffalos, and the four-horned and spiral-horned antelopes. The evolutionary relationship betwe ...

origin; modern formulations contain human thrombin. The two components are mixed immediately before application. The formulations also contain calcium salts. Formulations from different manufacturers may also contain

aprotinin The drug aprotinin (Trasylol, previously Bayer and now Nordic Group pharmaceuticals), is a small protein bovine pancreatic trypsin inhibitor (BPTI), or basic trypsin inhibitor of bovine pancreas, which is an antifibrinolytic molecule that inhibits ...

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as collage ...

plasminogen Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encode ...

, and factor XIII.

Factors affecting structure

Factors that influence dimensional structure of fibrin gel giving rise to fine or coarse gel: # Changing concentration of fibrinogen # Changing concentration of thrombin – increased concentration increases ultimate

tensile strength Ultimate tensile strength (UTS), often shortened to tensile strength (TS), ultimate strength, or F_\text within equations, is the maximum stress that a material can withstand while being stretched or pulled before breaking. In brittle materials t ...

and

Young modulus Young's modulus E, the Young modulus, or the modulus of elasticity in tension or compression (i.e., negative tension), is a mechanical property that measures the tensile or compressive stiffness of a solid material when the force is applied le ...

of gel # Changing concentration of calcium # pH # Temperature

History

A formulation with human thrombin was approved for medical use in the United States in March 2003, and in the European Union in October 2008.

References

External links

* {{DEFAULTSORT:Fibrin Glue Blood Surgery Adhesives