Fibrin

How is fibrin formed? (Stages)

The process of converting soluble fibrinogen into an insoluble fibrin gel takes place in several successive stages:

• Formation of monomers: The enzyme thrombin acts on fibrinogen, cleaving negatively charged A and B peptides (fibrinopeptides) from it. The loss of negative charge eliminates the electrostatic repulsion of molecules, resulting in the formation of fibrin monomer.
• Polymerization (aggregation): Complementary binding sites open up in the monomers. With the participation of $Ca^{2+}$ ions, weak non-covalent bonds arise between them. Self-assembly of molecules into a fibrin polymer (soluble fibrin) occurs. At this stage, the clot is still fragile.
• Stabilization (formation of insoluble fibrin): Enzymatic "cross-linking" is necessary to transform the gel into a dense thrombus. Transglutaminase (factor XIIIa, activated by thrombin) forms strong covalent amide bonds between glutamine and lysine radicals of adjacent monomers, as well as between fibrin and fibronectin. Tissue fibrinasess also participate in stabilization.
• Retraction: Final compression and compaction of the clot with the release of serum. It occurs with the participation of the platelet contractile protein (thrombostenin) and requires the presence of ATP.

How does fibrin cleavage occur?

The process of dissolving a fibrin thrombus is called fibrinolysis. It is necessary to clear the vessel lumen of fibrin deposits and prevent its occlusion.

• The main active enzyme is plasmin.
• Under the influence of plasmin, the peptide bonds of fibrin are broken.
• As a result, breakdown products are formed — peptides and amino acids.

Clinical significance and role in pathologies

In addition to normal hemostasis, fibrin and fibrin-like masses play a role in a number of pathological and physiological processes:

• Hyaline membranes: In respiratory distress syndrome of the newborn, fibrin forms the basis of membranes that form directly on the basement membrane at sites of epithelial damage. The membranes also contain tyrosine-α_1-antitrypsin and the $C_3$ complement component.
• Rheumatic diseases: Fibrin is an obligatory component of fibrinoid, a complex comprising proteins and polysaccharides of decaying collagen fibers, ground substance components, blood plasma, and cellular nucleoproteins. Fibrin is formed from fibrinogen under the action of tissue thrombokinase.
• Amniotic fluid embolism (AFE): In AFE, platelet-fibrin microclots form, blocking pulmonary capillaries and increasing pulmonary vascular resistance. AFE is accompanied by the development of disseminated intravascular coagulation (DIC) and blood clotting disorders; the clinical picture may include hypofibrinogenemia and depletion of clotting factors, leading to massive hemorrhage.
• Inflammatory processes: Fibrin deposits are found on the surface of abscesses, for example in ovarian pyovarium, and in alveolar exudate in chlamydial pneumonia.

Role of fibrinoid in pregnancy

Fibrinoid is a non-cellular fibrin-like mass formed from blood components and tissue breakdown products.

• Normal condition: During physiological pregnancy in the spiral arteries of the uterus, the muscle and elastic membranes are destroyed and replaced by a wide layer of fibrinoid. Langhans fibrinoid is localized on the surface of chorionic villi, while Rohr fibrinoid is located on the surface of septa bordering the blood lacunae.
• Pathology (gestosis): Atherosis develops — an excessive accumulation of fibrinoid in the arterial wall with the presence of numerous lipid-laden foamy macrophages. Pathology of the spiral arteries leads to insufficient blood supply to the placenta.

Class and exam questions

What else to study on this topic

• Fibrinogen and its structure
• Thrombin and the prothrombinase complex
• Fibrinolysis and functions of plasmin
• DIC syndrome and coagulopathies

Other topics in "Physiology concepts"

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