Uses
Tissue plasminogen activator has been used in a study to assess treatment risks of intracranial hemorrhage among patients with acute ischemic stroke. Tissue plasminogen activator has also been used in a study to investigate the successful treatment of early thrombosis of HeartWare left ventricular assist devices with intraventricular thrombolytics. Human tissue plasminogen activator has been used to study the effect of tyrosinase-related protein 2 (TRP-2) expression on melanin production in sheep.
General Description
Recombinant tPA (rtPA), alteplase (Activase), is identicalwith endogenous tPA. rtPA lacks a glycosyl residue atAsn184. At one time, rtPA was produced in two-chain formin CHO cultures. Now, large-scale cultures of recombinanthuman melanoma cells in fermenters are used to produce aproduct that is about 80% single-chain rtPA.
Alteplase is used to improve ventricular function followingan acute myocardial infarction, including reducing the incidenceof congestive heart failure and decreasing mortality.The drug is also used to treat acute ischemic stroke aftercomputed tomography (CT) or other diagnostic imaging hasruled out intracranial hemorrhage. rtPA is also used in casesof acute pulmonary thromboembolism and is being investigatedfor unstable angina pectoris.
Alteplase is supplied as powder for injection, and in reconstitutedform (normal saline or 5% dextrose in water) isintended for IV infusion only. The solution expires in 8 hoursat room temperature and must be prepared just before use.
Biochem/physiol Actions
tPA is a potent activator of fibrinolysis and converts plasminogen into plasmin and also initiates cell signaling. The plasminogen activation system may also be associated with degradation of amyloid fibrils. It is also known to mediate inflammatory and extracellular matrix remodeling processes and is predicted to participate in disease progression of intracranial aneurysm indicating brain vascular malformations. Upregulation of the gene is observed in aortic aneurysms.
