Thrombin

Thrombin is the central enzyme of blood coagulation in humans (including all vertebrates) and one of the blood coagulation factors (factor IIa). Thrombin belongs to the serine proteases and is similar to trypsin in its effect. Thrombin splits fibrinogen into fibrin and other fibrinopeptides. It also activates the blood clotting factors V, VII, VIII, XIII and, together with thrombomodulin, the protein C.

Thrombin has functions in inflammatory processes and wound healing. It is produced in the liver (see prothrombin below) and is found continuously in the blood plasma as a precursor (prothrombin). Defects in the thrombin gene (F2 gene) are the cause of dysprothrombinaemia

Furthermore, thrombin affects numerous cell systems. In order to unfold its effect in these cells, thrombin must bind to one receptor (thrombin receptor), which passes on the signals via coupled G-proteins (G-protein coupled receptors) within the cell. These receptors are called protease-activated receptors (PAR). The subtypes activated by thrombin are PAR 1,3, and 4.

By stimulating the migration of muscle cells from the media to the intima, thrombin stimulates the formation of neointima after damage.

Previously known thrombin activities

• Catalysis of fibrin formation from its precursor fibrinogen
• Activation of factor XIII to XIIIa (stabilization of fibrin into insoluble form)
• Activation of the factors V to Va, VIII to VIIIa, thus accelerating the coagulation process.
• Activation of factor XI to XIa and factor VII
• Promotes platelet aggregation by binding to receptors on the platelet surface. The receptors are activated by platelet receptor activating peptides (TRAP), peptides with 5-16 amino acids.
• Release of phospholipids and growth factors
• Stimulation of the synthesis of prostaglandins, thromboxane and thus platelet activating
• Promotion of the synthesis of prostacyclin (clotting antagonist)
• Inhibition of the activity of t-PA
• Activation of the tissue factor pathway inhibitor (TFPI)
• Inhibition of plasminogen activation
• Activation of protein C to protein Ca after binding to thrombomodulin on the membrane
• Stimulation of fibroblasts and smooth muscle cells for proliferation (mitogenic effect of thrombin) via their own thrombin receptors (protease-activated receptor) or by modulation of other growth factors.
• chemotactic effects on leukocytes and macrophages

Thrombin is bound to thrombin receptors, which belong to the family of G-protein coupled receptors. These receptors are called protease-activating receptors (PAR). The subtypes that are activated by thrombin are PAR 1, 3 and 4. A variety of functions are stimulated via these receptors.
Thrombin also acts on granulocytes, leukocytes, lymphocytes and macrophages. Furthermore, by stimulating the migration of muscle cells from the media to the intima, thrombin stimulates the formation of neointima after damage.

Only small amounts of free thrombin are found in the blood. Thrombin is only formed when tissue is injured by activating the prothrombin (factor II) formed in the liver under the action of vitamin K. Due to the interaction with antithrombin III, thrombin in the blood has only a very short half-life (a few minutes), whereby heparin accelerates this process considerably. Thrombinaemia, the occurrence of free thrombin and thus uncontrolled clotting is prevented by the body's own antithrombins.

1. HA Neumann (2014) The coagulation system. ABW-Wissenschaftsverlag GmbH Berlin pp. 53-54.