Fibrinolysis: tPA, plasminogen and plasmin
Fibrinolysis, the breakdown of fibrin (the protein strands forming a clot's meshwork), happens when activators such as tissue plasminogen activator (tPA) convert inactive plasminogen into plasmin, which digests fibrin.
Remember
Fibrinolysis clears an existing clot: tPA converts plasminogen to plasmin, and plasmin digests the fibrin. tPA is the activator and does not cut fibrin itself.
Memory aid
plasmin is the pair of scissors and tPA is the hand that picks them up
Picture plasmin as the scissors that cut fibrin and tPA as the hand that picks them up, so tPA starts the process but does not cut fibrin itself.
A clot should not outlast its usefulness. Once the vessel has healed, the body removes the clot by fibrinolysis, the breakdown of fibrin. Plasminogen is an inactive precursor (a form that stays switched off until it is needed). The liver mainly makes it, and it circulates in the blood.
Endothelial cells (the cells lining the blood vessels) release tissue plasminogen activator (tPA), which converts plasminogen into plasmin. Fibrin enhances this activation at the clot, so plasmin is made mainly where it is needed. Plasmin is a protease (an enzyme that cuts other proteins), and it breaks fibrin into fibrin degradation products, which are fragments swept away in the circulation.
tPA is an activator: plasminogen is what gets converted, not tPA, and tPA does not cut fibrin itself. Thrombin (the enzyme that makes fibrin from fibrinogen) and factor XIII (which chemically joins fibrin strands) build and strengthen the clot, whereas plasmin takes it apart.
Natural anticoagulants, such as antithrombin (which inhibits thrombin and factor Xa, another clotting enzyme), work differently. They oppose the formation of new fibrin in the first place, and they do not destroy a clot that already exists.
As a drug, tPA can dissolve thrombi (clots inside a vessel), but unwanted bleeding is a recognised side effect.
Key facts
- Enzyme
- plasmin digests fibrin into fibrin degradation products.
- Activator
- tPA from endothelial cells converts plasminogen to plasmin.
- Precursor
- plasminogen is inactive and is made mainly by the liver.
- Local action
- fibrin enhances the activation of plasminogen at the clot, so plasmin is made mainly where the clot is.
- Contrast
- natural anticoagulants oppose the formation of fibrin, whereas fibrinolysis removes fibrin already laid down.
- Clot builders
- thrombin makes fibrin from fibrinogen and factor XIII cross-links it, so both build and strengthen the clot.
- Drug use
- tPA can be given as a drug to dissolve thrombi, and bleeding is a recognised side effect.
Exam traps
- tPA does not cut fibrin itself, because it acts on plasminogen to make plasmin, and plasmin is the enzyme that digests fibrin.
- tPA is not converted into plasmin, because it is the activator and plasminogen is the inactive precursor that becomes plasmin.
- Factor XIII does not dissolve a clot, because it cross-links fibrin strands, which strengthens the clot and makes it harder to break down.
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