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 is necessary 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 the patient receives tPA; 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 emergencies, 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, correlate to the total exposure of tPA.
Cardiac dysrhythmias may occur when tPA is administered for NSTEMI and is related to the 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 the 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 treatment 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 there is no research on specific dosages. 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 nurses, pharmacists, and radiologists must be fully aware of their indications and contraindications. For these agents to be effective, not only do they require administration within a certain timeframe, but one also has to ensure that the patient has no condition that contraindicates the therapy. Also, 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]
There have been many clinical trials 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 a 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]
|||Grossberg JA,Rebello LC,Haussen DC,Bouslama M,Bowen M,Barreira CM,Belagaje SR,Frankel MR,Nogueira RG, Beyond Large Vessel Occlusion Strokes: Distal Occlusion Thrombectomy. Stroke. 2018 Jul [PubMed PMID: 29915125]|
|||Benoit JL,Khatri P,Adeoye OM,Broderick JP,McMullan JT,Scheitz JF,Vagal AS,Eckman MH, Prehospital Triage of Acute Ischemic Stroke Patients to an Intravenous tPA-Ready versus Endovascular-Ready Hospital: A Decision Analysis. Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors. 2018 May 30 [PubMed PMID: 29847193]|
|||Mac Grory B,Yaghi S, Updates in Stroke Treatment. Rhode Island medical journal (2013). 2018 Mar 1 [PubMed PMID: 29490322]|
|||Imbarrato G,Bentley J,Gordhan A, Clinical Outcomes of Endovascular Thrombectomy in Tissue Plasminogen Activator versus Non-Tissue Plasminogen Activator Patients at Primary Stroke Care Centers. Journal of neurosciences in rural practice. 2018 Apr-Jun [PubMed PMID: 29725176]|
|||Knecht T,Story J,Liu J,Davis W,Borlongan CV,Dela Peña IC, Adjunctive Therapy Approaches for Ischemic Stroke: Innovations to Expand Time Window of Treatment. International journal of molecular sciences. 2017 Dec 19 [PubMed PMID: 29257093]|
|||Liu H,Zheng H,Cao Y,Pan Y,Wang D,Zhang R,You S,Zhang X,Li S,Tong X,Liu CF,Wang Y, Low- versus Standard-Dose Intravenous Tissue-Type Plasminogen Activator for Acute Ischemic Stroke: An Updated Meta-Analysis. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2018 Apr [PubMed PMID: 29224744]|
|||Gilliland C,Shah J,Martin JG,Miller MJ Jr, Acute Limb Ischemia. Techniques in vascular and interventional radiology. 2017 Dec [PubMed PMID: 29224661]|
|||Vivien D, Can the benefits of rtPA treatment for stroke be improved? Revue neurologique. 2017 Nov [PubMed PMID: 28797689]|
|||Kepplinger J,Barlinn K,Deckert S,Scheibe M,Bodechtel U,Schmitt J, Safety and efficacy of thrombolysis in telestroke: A systematic review and meta-analysis. Neurology. 2016 Sep 27 [PubMed PMID: 27566746]|
|||Aoki J,Suzuki K,Suda S,Okubo S,Mishina M,Nishiyama Y,Sakamoto Y,Kimura K, In Hyperacute Recanalization Therapy, Early Hospital Arrival Improves Outcome in Patients with Large Artery Occlusion. European neurology. 2018 [PubMed PMID: 29986341]|
|||Man S,Zhao X,Uchino K,Hussain MS,Smith EE,Bhatt DL,Xian Y,Schwamm LH,Shah S,Khan Y,Fonarow GC, Comparison of Acute Ischemic Stroke Care and Outcomes Between Comprehensive Stroke Centers and Primary Stroke Centers in the United States. Circulation. Cardiovascular quality and outcomes. 2018 Jun [PubMed PMID: 29794035]|