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Tissue‐type plasminogen activator: a historical perspective and personal account
Author(s) -
Collen D.,
Lijnen H. R.
Publication year - 2004
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7933.2004.00645.x
Subject(s) - medicine , plasminogen activator , fibrinolysis , tissue plasminogen activator , thrombosis , pulmonary embolism , fibrin , t plasminogen activator , deep vein , myocardial infarction , cardiology , immunology
Summary. Over the past two decades tissue‐type plasminogen activator (t‐PA), the main physiological plasminogen activator, has been developed as a fibrin‐specific thrombolytic agent for the treatment of various thromboembolic diseases. Milestones in this development include: first purification of human t‐PA from uterine tissue, elucidation of the interactions regulating physiological fibrinolysis, thus providing a molecular basis for the concept of fibrin‐specific plasminogen activation, first animal models of thrombosis and pilot studies in patients supporting the therapeutic potential of t‐PA, cloning and expression of recombinant t‐PA providing sufficient amounts for large scale clinical use, and demonstration of its therapeutic benefit in large multicenter clinical trials, mainly in patients with acute myocardial infarction (AMI), but also in patients with massive pulmonary embolism, ischemic stroke, deep vein thrombosis and peripheral arterial occlusion. Genetically modified variants of t‐PA have been developed for bolus administration in patients with AMI.