Tissue plasminogen activator (abbreviated tPA or PLAT) is a protein involved in the breakdown of blood clots. Specifically, it is a serine protease () found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown. Because it works on the clotting system, tPA is used in clinical medicine to treat stroke.

Function

A simplified illustration demonstrates clot breakdown (fibrinolysis), with blue arrows denoting stimulation, and red arrows inhibition.

The classic role of tPA is in the clotting system. Specifically, tPA catalyzes the conversion of plasminogen into plasmin. It does so by cleaving the single-chained plasminogen into two chains. These two chains are linked by a disulfide bond and the resulting molecule is called plasmin.

Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding. Decreased activity leads to hypofibrinolysis which can result in thrombosis or embolism.

Tissue plasminogen activator also plays a role in cell migration and tissue remodeling.

Genetics

Tissue plasminogen activator is a protein encoded by the PLAT gene, which is located on chromosome 8. The primary transcript produced by this gene undergoes alternative splicing, producing three distinct messenger RNAs.

Clinical applications

Recombinant tPA is used in diseases that feature blood clots, such as pulmonary embolism, myocardial infarction and stroke. To be effective, tPA must be administered within the first three hours of the event to be given intravenously, or within six hours to be administered through an arterial catheter directly to the site of occlusion. The guideline in Ontario, Canada hospitals for ischemic strokes is that tPA must be given within 3 hours of the onset of symptoms. Because of this, only about 3% of patients qualify for this treatment. tPA appears to show benefit not only for large artery occlusions but also for lacunar strokes. Since tPA dissolves blood clots, there is risk of hemorrhage with its use.

Recently tPA has been used to dissolve thrombi associated with ischemic strokes and brain injury.

In addition, people with frostbite that were treated with tPA had fewer amputations than those that were not.^[1]

See also

• Thrombolysis
• Ultrasound-Enhanced Systemic Thrombolysis

References

Further reading

External links

• http://www.americanheart.org/presenter.jhtml?identifier=4751
• Widening the Window : Strategies to buy time in treating ischemic stroke - Scientific American Magazine (August 2005)

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