FDA-approved indications for alteplase include pulmonary embolism, myocardial infarction with ST-segment elevation (STEMI), ischemic stroke when given within 3 hours of the start of symptoms, and re-establishment of patency in occluded intravenous (IV) catheters.
Common off-label indications include:
The dosing and administration of tPA are specific to the indication.
FDA Approved Indications
Ischemic Stroke: The only blood test that should be done before tPA usage is the blood glucose level. If the patient is on anticoagulation like coumadin then only we should do PT, PTT, and INR etc. The benefit of tPA depends a lot on time. The sooner tPA is given, the better are the outcomes.
IV Catheter Occlusion
Pediatric Pleural Effusions
Prosthetic Valve Thrombosis
Alteplase is administered intravenously as a bolus injection or infusion. In emergency situations, it is reasonable to administer tPA through intraosseous access.
Bleeding associated with alteplase therapy can be divided into two broad categories. Internal bleeding includes intracranial bleeding (0.4% to 15.4%), retroperitoneal bleeding (less than 1%), gastrointestinal (GI) bleeding (5%), genitourinary bleeding (4%), and respiratory bleeding. Superficial or surface bleeding is observed mainly at invaded or disturbed sites such as venous cutdowns, arterial punctures, and recent surgical intervention sites. Less serious spontaneous bleeding includes ecchymosis (1%), gingival bleeding (less than 1%), and epistaxis (less than 1%). In clinical studies of adult patients with acute ischemic stroke (n = 624), a higher incidence of intracranial bleeding, especially symptomatic intracranial bleeding, was seen in patients receiving alteplase compared to placebo (total intracranial bleeding 15.4% versus 6.4%, p < 0.01; symptomatic intracranial bleeding 8% versus 1.3%, p < 0.01). However, there was no increase in the incidence of 90-day mortality or severe disability in patients receiving alteplase. Studies indicate that the incidence of intracranial bleeding is dose-related, with the greatest percentage occurring at a dosage of 150 mg (1.3%) compared to 100 mg (0.4%). Rates of adverse events including bleeding are related to the total exposure of tPA.
Cardiac dysrhythmias may be noted when tPA is administered for NSTEMI and is related to re-establishment of tissue perfusion rather than drug exposure.
Allergic reactions including anaphylactic-type reactions are possible following exposure to tPA. Various sources of tPA have varying levels of antigenicity. See “streptokinase” for further discussion. The rapid conversion of plasminogen to plasmin signals a complement cascade leading to mast cell degranulation and subsequent anaphylactic reaction.
A 2016 update was published by the American Heart Association to guide tPA inclusion and exclusion criteria for the management of ischemic stroke. The following list includes the most recent absolute and relative contraindications for therapy as determined by the AHA.
Relative Exclusion Criteria
Recent experience suggests that under some circumstances, with careful consideration and weighing of risk to benefit, patients may receive fibrinolytic therapy despite 1 or more relative contraindications. Consider risk to the benefit of intravenous rtPA administration carefully if any of these relative contraindications are present:
There are no therapeutic drug monitoring recommendations that pertain to the efficacy of tPA therapy. If prolonged off-label therapy is occurring in the event of catheter-directed therapy or repeated dosing in valve thrombosis serial imaging of the thrombus is reasonable. The safety profile is best monitored by prothrombin time (PT), partial thromboplastin time (PTT), Hemoglobin, and hematocrit to assess ongoing bleeding. Of note, fibrinogen levels may be an indicator of increased bleed risk for values less than 150mg/dL.
There is no direct reversal agent for the potentially major bleeding that may occur during tPA therapy. Commonly employed strategies include anti-fibrinolytic therapy such as tranexamic acid or aminocaproic acid though no specific dosages have been studied. If fibrinogen levels are less than 150mg/dL, there may be added benefit from fresh frozen plasma or cryoprecipitate. Cryoprecipitate should be used without any delay and monitor the fibrinogen level closely.
There is no longer any question about the effectiveness of thrombolytic agents for the treatment of several medical disorders, but it is vital that nurses, pharmacists, and radiologists be fully aware of their indications and contraindications. For these agents to be effective not only do they have to be administered within a certain time period, but one also has to ensure that the patient has no condition that contraindicates the therapy. In addition, the nurse should educate the patient about the procedure, the need to remain at bed rest for several hours after the procedure and the need to constantly monitor for bleeding. Plus, the pharmacist must be familiar with the recent novel anticoagulants and any possible interactions with the thrombolytic drugs. Only through close communication and constant vigilance between the various healthcare professionals can the serious complications of these drugs be prevented. (Level V)
Many clinical trials have been undertaken to determine the effectiveness of thrombolytic agents in patients with acute myocardial infarction, pulmonary embolism, acutely ischemic limb, and an embolic stroke. When used to treat acute MI, embolic stroke and pulmonary embolism, the outcomes are fair to good. The biggest drawback to this therapy is patient delay in arriving at the emergency room or a delay in diagnosis. These drugs have saved many lives and are cost-effective and reduce hospital stays. (Level II)
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