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Alteplase is a thrombolytic agent that is manufactured by recombinant DNA technology.It is FDA approved for use in acute ischemic stroke, pulmonary embolism, acute myocardialinfarction, and occluded catheters. Off-label indications include catheter-directed thrombolysis inthe treatment of peripheral arterial occlusive disease and deep vein thrombosis. (Reed, Kerndt, & Nicolas, 2020).
Mechanism of Action
Alteplase is a fibrinolytic agent; it also is referred to as tissue plasminogen activator(tPA). Alteplase converts plasminogen to the proteolytic enzyme plasmin, which lyses fibrin aswell as fibrinogen. Intravenous alteplase is cleared primarily by the liver with an initial half-life of fewer than 5 minutes and a terminal half-life of 72 minutes. When alteplase 2 mg is instilled into occluded catheters to restore catheter function, it is unlikely that plasma will attain pharmacologic concentrations of alteplase. (Reed, Kerndt, & Nicolas, 2020).
Monitoring
Patients require assessment for bleeding and hypersensitivity reactions. Neurological status and blood pressure require monitoring during intravenous therapy. Laboratory parameters to follow include hemoglobin, hematocrit, platelets, fibrinogen, and activated partial thromboplastin time. If serious bleeding occurs, stop the alteplase therapy and provide supportive care. If a hypersensitivity reaction occurs, stop the alteplase and provide supportive therapy such as antihistamines and corticosteroids. Coagulation tests may be unreliable during alteplase therapy because alteplase may degrade fibrinogen in blood samples. (Reed, Kerndt, & Nicolas, 2020).
Side Effects
Side effects of alteplase include bleeding, angioedema, anaphylaxis, and fever. The risk of bleeding is highest in patients with the following conditions: recent intracranial hemorrhage, major surgery, cerebrovascular disease, recent trauma or major bleeding, uncontrolled hypertension, acute pericarditis, hemorrhagic ophthalmic conditions, advanced age, concurrent anticoagulant or antiplatelet agents, and any coagulopathy that makes patients more susceptible to bleeding. There have been case reports of cholesterol embolization in patients treated with thrombolytics, including alteplase. (Reed, Kerndt, & Nicolas, 2020).
Drug Interactions
Alteplase breaks down clots and thereby interferes with the body’s ability to stop bleeding. Therefore, drugs which also interfere with the body’s ability to form blood clots (or the clot-promoting effects of platelets) increase the risk of bleeding in patients receiving alteplase. Such drugs include:
Warfarin (Coumadin, Jantoven).
Aspirin, and
nonsteroidal anti-inflammatory drugs (NSAIDs), for example,
Ibuprofen (Motrin, Advil)
Naproxen (Naprosyn, Aleve)
Nabumetone (Relafen), and
platelet inhibitors such as clopidogrel (Plavix), prasugrel (Effeint), cangrelor (Kengreal), ticagrelor (Brilinta). (Ogbru & Marks, 2020).
