Tissue Plasminogen activator (t-PA)

Most important kind of plasminogen activator.

Synthesized primarily by endothelial cells.

Most active when attached to fibrin.

Targets fibrinolytic enzymatic activity to sites of recent clotting making it useful therapy for thromboembolism.

A serine protease that acts by enhancing the conversion of the inactive plasminogen to active plasmin.

Plasmin acts on fibrin clots, causing lysis.

Activity of t-PA is greatly enhanced in the presence of fibrin with increased fibrinolysis, particularly at the site of thrombosis.

In vivo released by endothelial cells and when administered exogenously it is derived from recombinant DNA technology.

Unlike first generation plasminogen activators streptokinase and urokinase, recombinant rt-PA is fibrin-selective and preferentially activates fibrin bound plasmnogen.

rt-PA is inhibited by plasminogen activator inhibitor type I (PAI-1) in plasma.

PAI-1 capacity to bind rt-PA is rapidly exceeded when the drug is administered systemically, thereby increasing the risk of bleeding.

Half-life of rt-PA in the circulation is about four minutes.

Intravenous t-PA is the only effective treatment to improve the outcomes for acute ischemic stroke.

tPA is the only level 1A treatment for acute ischemic stroke.

TPA given intravenously for acute ischemic stroke carries the risk of symptomatic intracranial hemorrhage.

Intravenous tissue plasminogen activator is the only proven therapy for reperfusion in ischemic stroke.

Intravenous t-PA for stroke is associated with potentially life-threatening complications in 2.4-8.8% of cases.

IV TPA compared with no reperfusion has been demonstrated in randomized trials to improve three month functional outcomes after acute ischemic stroke, and one year-1.5 year functional outcomes.

In a retrospective study of 61,426 patients with acute ischemic stroke treated with intravenous tissue plasminogen activator, longer door-to-needle times were significantly associated with higher all-cause mortality at one year and a higher likelihood of all-cause readmission at one year (Man S).

Of patients with acute ischemic stroke only 2-8% receive this therapy.

There is relatively low rate of symptomatic cerebral hemorrhage with the use of TPA, typically 4-5%.

Following treatment with intravenous TPA the rate of symptomatic intracerebral hemorrhage is about 1% higher among patients receiving warfarin with an INR of 1.7 or less, compared with patients that were nottaking warfarin ( 5.7% versus 4.6%, respectively.

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