Tissue plasminogen activator

Overview
Tissue plasminogen activator (abbreviated PLAT or tPA) is a serine protease normally found on the surface of endothelial cells of veins, capillaries, the pulmonary artery, heart, and uterus, and is secreted after vascular injury. It converts the proenzyme plasminogen to plasmin, a fibrinolytic enzyme. Plasminogen is synthesized as a single chain, which is cleaved by PLAT into the two chain disulfide linked plasmin.

Function
This enzyme plays a role in cell migration and tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding; decreased activity leads to hypofibrinolysis which can result in thrombosis or embolism.



Gene
Alternative splicing of the PLAT gene, PLAT, produces three transcripts.

Clinical applications
Recombinant PLAT is used in diseases that feature blood clots, such as myocardial infarction and stroke. To be effective, PLAT 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 PLAT 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.