Tissue-type plasminogen activator

1A5H, 1BDA, 1PK2, 1PML, 1RTF, 1TPG, 1TPK, 1TPM, 1TPN, 5BRR532718791ENSG00000104368ENSMUSG00000031538P00750P11214NM_033011NM_000930NM_000931NM_001319189NM_008872NP_000921NP_001306118NP_127509NP_032898Tissue-type plasminogen activator, short name tPA, is a protein that facilitates the breakdown of blood clots.

Human tPA is encoded by the PLAT gene, and has a molecular weight of ~70 kDa in the single-chain form.

tPA is used in some cases of diseases that feature blood clots, such as pulmonary embolism, myocardial infarction, and stroke, in a medical treatment called thrombolysis.

[7][8] Many national guidelines including the AHA have interpreted this cohort of studies as suggesting that there are specific subgroups who may benefit from tPA and thus recommend its use within a limited time window after the event.

[10] Similarly in the United States, the window of administration used to be 3 hours from onset of symptoms, but the newer guidelines also recommend use up to 4.5 hours after symptom onset, depending on the patient's presentation, past medical history, current comorbidities and medication usage.

[12][13] Use of tPA in the United States in treatment of patients who are eligible for its use, have no contraindications, and arrival at the treating facility less than 3 hours after onset of symptoms, is reported to have doubled from 2003 to 2011.

There is significant debate mainly in the emergency medicine community regarding recombinant tPA's effectiveness in ischemic stroke.

The NNT Group on evidence-based medicine concluded that it was inappropriate to combine these twelve trials into a single analysis, because of substantial clinical heterogeneity (i.e., variations in study design, setting, and population characteristics).

[19] The NNT Group notes that the case for the 3-hour time window arises largely from analysis of two trials: NINDS-2 and subgroup results from IST-3.

[20] In the UK, concerns by stroke specialists have led to a review by the Medicines and Healthcare products Regulatory Agency.

[21] Pulmonary embolism (blood clots that have moved to the lung arteries) is usually treated with heparin generally followed by warfarin.

[25] Tissue-type plasminogen activators were initially identified and isolated from mammalian tissues after which a cDNA library was established with the use of reverse transcriptase and mRNA from human melanoma cells.

In patients with ischemic strokes, decreased tPA activity was reported to be associated with an increase in plasma P-selectin concentration.

A simplified illustration demonstrates clot breakdown ( fibrinolysis ), with blue arrows denoting stimulation, and red arrows inhibition.
In vivo mechanism of action of tPA within the fibrinolytic system. tPA can go one of three ways in the body; (1) uptaken by the liver and cleared through receptors therein, (2) inhibited by a plasminogen activator inhibitor (PAI) and subsequently cleared from the liver, or (3) through the activation of plasminogen to plasmin for degradation to result in fibrin degradation product. [ 37 ] [ 38 ]
A theoretical full-length model of t-PA. The finger domain is in red, the EGF-like domain in green, the kringle 1 and 2 domains in blue and yellow respectively, and the serine protease domain in magenta.
A 360 view of t-PA showing its structure.