tissue plasminogen activator
Meaning of tissue plasminogen activator: The body's own clot-dissolving switch, copied in the laboratory to become the drug given to reopen a blocked artery during a stroke.
Definition of tissue plasminogen activator
Tissue plasminogen activator is an enzyme released by the cells lining blood vessels that begins the breakdown of clots. It converts plasminogen, an inactive protein trapped within the clot, into plasmin, which cuts up the fibrin mesh holding the clot together. Manufactured versions are given as drugs to dissolve clots blocking arteries in the brain, the heart or the lungs.
How does it find the clot?
It does not travel to the clot so much as switch on once it is there. Alone in the bloodstream it converts plasminogen only sluggishly. Both it and plasminogen bind to fibrin, the mesh of protein strands that holds a clot together, and once the two are held side by side on that mesh the reaction accelerates enormously. So most of the dissolving happens where fibrin is, rather than everywhere in the circulation at once. That behavior separates this enzyme from the older clot-busting drugs, which switched on plasminogen indiscriminately and stripped clotting protein from the whole bloodstream.
Where are the manufactured forms used?
| Setting | What the drug is meant to do |
|---|---|
| Stroke from a blocked artery | Reopen the vessel within a narrow window after symptoms begin |
| Large clot in the lung | Relieve the strain on the right side of the heart |
| Heart attack | Restore flow where catheter treatment is unavailable |
| Blocked central line | Clear the clot inside the catheter, at a tiny dose |
The laboratory versions are engineered copies rather than the natural protein, described as recombinant tissue plasminogen activator, and some are altered to last longer so they can be given as one injection. A different member of the same family, the urokinase type, is measured in tumor tissue as a marker of outlook, which is a separate matter from treatment.
What limits its use?
Bleeding, and the clock. The drug cannot tell a useful clot from a harmful one, so it can reopen a healing wound, an ulcer or a recently punctured vessel, and bleeding into the brain is its most feared complication. That is why a stroke is imaged first: a stroke caused by bleeding can look much like one caused by a blockage at the bedside, and dissolving clots in that situation is catastrophic. The window after symptoms begin is narrow because brain tissue starved of blood turns fragile, so late reopening carries more hazard than benefit. Its natural life in the blood is only minutes, and the body makes an inhibitor that shuts it down.
Also known as
Used in a sentence
Tissue plasminogen activator was administered after imaging excluded hemorrhage.
Good to know
Tissue plasminogen activator is an established treatment rather than an experimental one, and the plasminogen activator studied as a tumor marker is the urokinase type, a related but distinct enzyme.