Tissue plasminogen activator

  • CAS Number: 105857-23-6

The tissue-specific plasminogen activator ( Sheet tissue-type plasminogen activator, t -PA) is an enzyme which is released from the endothelial cells of the vessel wall and acts as an endogenous activator of fibrinolysis. It is a serine protease that converts plasminogen directly to plasmin, thus inhibiting blood clotting. Blood formed inhibitors of t-PA are known as plasminogen activator inhibitor.

A genetically engineered variant of alteplase ( recombinant tissue - type plasminogen activator, rt- PA) is used therapeutically for the resolution of thrombus ( thrombolysis ).

Alteplase

Alteplase is the proprietary name of the recombinant tissue plasminogen activator (rt -PA). The drug is used as a fibrinolytic agent to dissolve blood clots (thrombi ) in various vascular diseases ( thrombolysis ).

The drug alteplase mimics the action of natural tissue-specific plasminogen activator. Related directly acting fibrinolytic substances are tenecteplase and reteplase. Similar, but indirectly also affect fibrinolytic streptokinase and urokinase.

A special feature of tPA based on the fact that it can still circulate systemically, but its activity fully developed only after binding to a fibrin clot. In addition, it is mined there after some time itself proteolytically. Thus it is regulated, in contrast to bacterial enzymes highly locally -acting and effective, what was originally promised a superior therapeutic concept. The recombinant r -tPA also showed exactly this behavior in pre-clinical animal studies. All the greater was the disappointment when in the clinical tests, the 1000x relative dose (→ relative = relative to body weight ) had to be used in humans. It can be assumed that this is to the rest of the activity of tPA, which is not subject to the above -mentioned scheme, which the superiority of the r -tPA compared with the bacterial enzymes is gone. Given the higher costs by a multiple of r -tPA compared with the classical bacterial enzymes, this should have been the end for an r- tPA based therapy. The company Genentech, depended on the existence at that time exclusively by their product r -tPA, however, was able to demonstrate in an extensive clinical trial that, based on a large cohort patients after treatment with the alternative product 100 patients died after treatment with r- tPA "only" 99 patients.

Indications

Applies alteplase in the following syndromes:

  • Heart attack (if a coronary intervention with appropriate recanalization within acceptable periods of time is not available)
  • Acute ischemic stroke
  • Acute massive pulmonary embolism

Basically need to distinguish between local and systemic thrombolytic therapy. With local thrombolysis the fibrinolytic is injected by catheter intervention close to the site of action, eg an acutely occluded by a blood clot leg artery. In the systemic fibrinolytic the thrombolysis is injected via a peripheral vein in the systemic circulation.

The use of all fibrinolytic substances a strict risk - benefit analysis must be carried out, since serious side effects may occur in the form of uncontrollable and potentially fatal bleeding.

Trade names

The enzyme rt -PA ( alteplase ) is available in Germany, Austria and Switzerland under the name of alteplase in the trade.

Protein isoform Human Genome Organisation CAS registry number Anatomical Therapeutic Chemical Classification System MEROPS Trypsin Organism Endothelium Hemostasis Plasminogen activator inhibitor-1 International Nonproprietary Name Active ingredient
28383
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