tPA / Tissue plasminogen activator

tPA / Tissue Plasminogen Activator

tPA or Tissue plasminogen activator is a serine protease which is responsible for breakdown of blood clots. It is found on endothelial cells of  blood vessels. tPA catalyzes the conversion of plasminogen to plasmin, the important enzyme which causes breakdown of clot.

tPA produced by recombinant biotechnology techniques are called as recombinant tissue plasminogen activator (rtPA) and some example are alteplase, reteplase, and tenecteplase which are specific rtPA . In the treatment of embolic or thrombotic stroke, these manufactured tPAs have a major role. These drugs are contraindicated in hemorrhagic stroke and head trauma. Aminocaproic acid is the antidote for tPA toxicity.

Medical uses

tPA is mainly used in pathologies caused by blood clot such as myocardial infarction,  stroke, pulmonary embolism. Treatment with tPA is called thrombolysis. The most common use is for ischemic stroke. tPA can be administered systemically or directly into the site of clot using arterial catheter.  

  • Systemically administration
    • Acute ischemic stroke
    • Acute myocardial infarction 
    • Mmost cases of acute massive pulmonary embolism
  • Administered through an arterial catheter
    • Peripheral arterial thrombi
    • Thrombi in the proximal deep veins of the leg.

Recombinant tPA is commonly called as r-tPA and sold under multiple brand names.

  • Activase (Alteplace)
    • Treatment of  ST-elevation with Myocardial Infarction (STEMI)
    • Acute ischemic stroke (AIS)
    • Acute massive pulmonary embolism
    • Central venous access devices (CVAD
  • Reteplase
    • Acute myocardial infarction – due to easy administration and faster thrombolysis than Alteplase. 
  • Tenecteplase
    • Acute myocardial infarction -Has fewer bleeding complications
  • Desmoteplase Currently under clinical development.

Mechanism of action

tPA and plasmin are two main enzymes of the fibrinolytic pathway in which tPA mediated plasmin conversion occurs. Increased activity  of enzymes causes hyperfibrinolysis, thus causes excessive bleeding and increased permeability of vessels. Hypofibrinolysis occurs due to decreased enzymatic activity that can end up in thrombosis or embolism.

tPA / Tissue plasminogen activator also plays a role in tissue remodeling and cell migration.

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