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Encyclopedia > Thrombin

Thrombin (activated Factor II) is a coagulation protein that has many effects in the coagulation cascade. It is in fact an enzyme of the serine protease type (EC 3.4.21.5 (http://www.expasy.org/cgi-bin/nicezyme.pl?3.4.21.5)), and therefore acts by cleaving proteins at certain locations. Its main action is to turn fibrinogen into fibrin.

Contents

Generation

Thrombin is produced from prothrombin, which is essentially the inactive state of this protein and produced in the liver. Activated coagulation factors X and V are responsible for the conversion of prothrombin to thrombin. Prothrombin is also called factor II and requires vitamin K to be produced. Deficiency of vitamin K or administration of warfarin impair thrombin function.


Genetics

The prothrombin gene is located on the eleventh chromosome (11p11-q12).


Action

Coagulation cascade

The active form of factor II, thrombin, has a number of effects on other coagulation proteins. Its most direct effect on clot production is its conversion of fibrinogen into fibrin, but it also feeds back on a number of locations in the coagulation cascade.


Thrombin activates factor XI and factor VIII, increasing the flow through the intrinsic pathway of coagulation. Thrombin also activates factor V of the common pathway, which quickly increases its own production from prothrombin.


Factor XIII, the coagulation protein that stabilises the fibrin clot, is also activated. This increases the speed the fibrin in the clot is covalently linked to itself.


Platelets

As well as the coagulation pathways, thrombin also promotes platelet aggregration.


Inhibitors and fibrinolysis

Interestingly, thrombin activates protein C, which inhibits coagulation. This happens on the surface of the endothelium, on a protein called thrombomodulin. The formation of activated protein C is important in the digestion of coagulation factors Va and VIIIa, thus thrombin both cleaves fibrinogen to form fibrin and slows down the clotting process (presumably so it doesnt get out of hand).


Apart from this, thrombin also initiates fibrinolysis (together with Factor XII).


Role in disease

Activation of prothrombin into thrombin is crucial in physiological and pathological coagulation. Various rare diseases of prothrombin have been described.


An apparently quite common disorder (up to 5% in Western patients) is the substitution of adenine for guanine at position 20210 of the prothrombin gene. Although this falls outside the reading frame for the protein, it leads to high levels of prothrombin and a possibly increased risk of thrombosis (Poort et al 1996).


References

  • Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3' untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996;88:3698-703. PMID 8916933.


Cardiovascular system - Blood
Red blood cells - White blood cells - Platelets - Blood plasma
White blood cells
Granulocytes (Neutrophil granulocytes, Eosinophil granulocytes, Basophil granulocytes) - Lymphocytes - Monocytes
Coagulation
Coagulation factors: - Fibrin - Thrombin - FVII - FVIII - FIX - FXII - FXIII - HMWK - vWF
Inhibitors: Antithrombin - Protein C - Protein S - TFPI
Fibrinolysis: Plasmin - tPA/uPA - PAI-1/2 - α2-AP

  Results from FactBites:
 
Thrombin (1143 words)
This was further confirmed by the ability of thrombin to mimic LPS toxicity when infused in the portal vein (5) or when added to the perfusate in the isolated liver model (preliminary results), and by the ability of antithrombin III to reduce the symptoms and improve the survival rate of patients with septic shock (29).
Thus, thrombin appears to be an important mediator of the LPS-induced hepatocellular necrosis that acts after the accumulation of inflammatory cells in the liver and the release of certain inflammatory mediators (TNF-a).
The earliest identified function of thrombin is the cleavage of fibrinogen into fibrin monomers and the activation of the fibrin-stabilizing factor (factor XIII) and protein C. Clotted blood is a meshwork of insoluble fibrin threads that traps blood cells and serum.
Thrombin - Wikipedia, the free encyclopedia (585 words)
Thrombin (activated Factor II (IIa)) is a coagulation protein that has many effects in the coagulation cascade.
Thrombin is produced by the enzymatic cleavage of two sites on prothrombin by activated Factor X (Xa).
Thrombin activates protein C, an inhibitor of the coagulation cascade.
  More results at FactBites »

 
 

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