Fibrinolysis

Fibrinolysis occurs after coagulation, and is the process where a fibrin clot is broken down.

Physiological fibrinolysis

The main enzyme of fibrinolysis is plasmin. Plasmin cleaves fibrin in multiple locations and acts to dissolve a fibrin clot.

Plasmin is produced in an inactive form, plasminogen, in the liver. Although plasminogen cannot cleave fibrin, it still has an affinity for it, and is incorporated into the clot when it is formed.

Tissue plasminogen activator (tPA) is what converts plasminogen to plasmin. Thus allowing fibrinolysis to occur. This is released into the blood by the cells of the healthy endothelium neighbouring the clot.

tPA cleaves plasminogen, which starts fibrinolysis, though tPA is inhibited by other chemicals in the bloodstream. Alpha-2-antiplasmin, and plasminogen activator inhibitor (PAI) serve to turn off tPA.

When plasmin breaks down fibrin, a number of soluble parts are produced. These are called fibrin degradation products (FDPs). FDPs compete with thrombin, and so slow down the conversion of fibrinogen to fibrin (and thus slows down clot formation). This effect can be seen in the TCT or thrombin clotting time test, which is longer in a person who has recently undergone fibrinolysis.

FDPs, and a specific FDP, the D-dimer, can be measured using antibody-antigen technology. This is more specific than the TCT, and virtually confirms that fibrinolysis has occurred.

It is important to know if fibrinolysis has recently happened, as this can indicate deep vein thrombosis or a pulmonary embolism.

Treatment using fibrinolysis

Fibrinolytic drugs are given after a heart attack to dissolve the thrombus blocking the coronary artery or in stroke to reperfuse the affected part of the brain. The process is called thrombolysis.

The two main drugs that are used are:

• Streptokinase - produced by alpha-haemolytic Streptococcus species. This is very effective and cheap, though since it is a bacterial product, the body will build up an immunity to it. For this reason, it is usually given only for a person's first heart attack. It binds to plasminogen, forms enzyme complex. Complex catalyzes conversion of plasminogen to active plasmin.
• Recombinant tPA - also very effective, but very expensive. It does not have the immune problems that streptokinase is associated with. It binds to fibrin first, then complex binds plasminogen forming triad.

Other drug:

• Urokinase - synthesized by tubular epithelial cells in human kidney. It directly cleaves circulating plasminogen to plasmin. However, it lacks specificity like streptokinase and expensive.