About TPA / Tissue Plasminogen Activator:
TPA or tissue plasminogen activator is a protein that is part of the breakdown blood clots process.
The purpose of TPA (also sometimes called PLAT) is to break down clots that form in blood vessels around the body. It is one of the essential enzymes for healthy cardiovascular function.
When functioning as an enzyme, TPA catalyzes the conversion of plasminogen into plasmin. For this reason, it has a large number of critical medical uses. For instance, TPA is sometimes used in the aftermath of a pulmonary embolism or myocardial infarction. It is also sometimes used in cases of ischaemic stroke.
Medical practitioners inject the compound into the body of the patient in the hope that it will break down the clot and help to restore normal artery function.
The consensus on the administration of TPA is that the benefits outweigh the risks based on the results of a meta-analysis. Reevaluation of that analysis, however, found that it was flawed. Researchers from the NNT Group argued that the studies were too different from one another for them to be collected together and analyzed as a group. Thus, while the overall group of studies showed benefits to patients, analysis of the individual studies painted a very different picture.
Of the twelve studies, only two showed a beneficial effect from the administration of TPA. Four saw significant harm, forcing practitioners to end their trials. The rest showed no benefit at all.
The research indicates, therefore, that the action of TPA on blood vessels is not yet fully understood. While it appears to have an anti-clotting effect, it may also have off-target effects that impinge on a patient’s ability to recover from treatment. These off-target effects could include the interactions we discuss briefly in the next section.
Tissue Plasminogen Activator Interactions
TPA is known to interact with a range of compounds throughout the body, including fibrinogen alpha chain, LRP1, and SERPINI1.
TPA and plasmin are two critical enzymes in the fibrinolytic pathway that generate TPA-mediated plasmin.
Researchers believe that TPA cleaves zymogen plasminogen at the Arg561 - Val 562 peptide bond, creating serine protease plasmin.
If the activity of the enzyme is too high, it can result in hyperfibrinolysis, which leads to excessive vascular bleeding and an increase in the propensity of the blood vessel walls to leak.
If the activity of the enzyme is too low, it cannot break down clots, leading to an increased chance of embolisms. Thus, the blood is thinner when TPA is overactive and thicker when it is less active.
After being produced in the body, TPA takes one of three routes to take its effect on the blood vessels.
First, the liver can absorb TPA and clear it from the body using the LDL receptor-related protein, a particular type of scavenger protein present in the blood.
Second, TPA can bind to the plasminogen activator inhibitor, knocking it out of action. And finally, it can link to plasminogen, cleaving the plasmin.