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FIBRINOLYTIC SYSTEM

FIBRINOLYTIC SYSTEM

What does the fibrinolytic system do? fibrin clot

The fibrinolytic system is the other component of haemostasis. As the picture alongside shows, haemostasis results in the formation of a fibrin clot at the site of a wound; the ingredients of a fibrin clot include red blood cells, platelets and cross-linked fibrin (which is string-like) that holds the clot together.

The fibrinolytic system is the regulatory system which is responsible for returning the blood vessel to normal: it does this by repairing the injured site and dissolving the fibrin of the clot.

How does the fibrinolytic system work? 

Smart Art Graphic: Original
Smart Art Graphic: Original

The fibrinolytic system is influenced by the activation of plasmin.  Plasmin, as the Smart Art Graphic alongside demonstrates, is designed to degrade fibrin from the clot into soluble products which can be taken away in the circulation and are ultimately excreted by the kidneys and the liver. The fibrin degradation products serve several functions:

  • Work against thrombin, hence they prevent the formation of fibrin
  • Interferes with the cross-linkage of fibrin molecules, hence it cannot form the net-like structure seen above.
  • Prevents primary haemostasis by preventing platelets from gathering together at the site of a wound
  • May destroy F1 (fibrinogen), FV (5) and FVIII (8)

How is plasmin activated? 

Smart Art Graphic: Original
Smart Art Graphic: Original

Like its counterpart fibrin within clotting, plasmin is a zymogen: a zymogen  requires an enzyme to be converted from the inactivated product (often indicated with the suffix -ogen) to the active form. The Smart Art Graphic alongside demonstrates how the inactivated product of fibrinogen requires thrombin to be converted into fibrin. Plasmin acts the same way: it requires plasminogen activators to be successfully converted into plasmin, and this plasmin then can act on fibrin unless something puts on the brakes.

 

Smart Art Graphic: Original
Smart Art Graphic: Original

What puts the brakes on the fibrinolytic system? 

Smart Art Graphic: Original
Smart Art Graphic: Original

There are several products that help put the brakes on the fibrinolytic system: plasminogen activator inhibitors or PAIs, alpha-2-antiplasmin and thrombin-activated fibrinolysis inhibitor or TAFI. They all act on different levels to prevent the fibrinolytic system from working.

  • As the Smart Art Graphic below demonstrates, PAIs stop the action of plasminogen activators, thereby stopping the formation of plasmin. These inhibitors are made on endothelial and smooth muscle cells or in white blood cells.
    Smart Art Graphic: Original
    Smart Art Graphic: Original
  • Alpha-2-antiplasmin neutralizes free plasmin.
  • TAFI controls the fibrinolytic system by preventing the breakdown of fibrin into fibrin degradation products.