alteplase (Activase)
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Introduction
Tradename: Activase.
Indications
- arterial thrombosis
- post myocardial infarction clot lysis
- within 4-6 hours of symptom onset
- ongoing symptoms
- unstable angina
- benefit over streptokinase in middle aged men with anterior myocardial infarction
- acute ischemic stroke: within 4.5 hours of onset[7][8][10][12]
- recent use of direct-acting oral anticoagulants not associated with increased risk or intracranial hemorrhage among patients with acute ischemic stroke treated with alteplase[20]
- occluded AV cannula[18]
- post myocardial infarction clot lysis
- venous thrombosis
- hemolytic uremic syndrome[18]
Contraindications
- absolute contraindications
- previous hemorrhagic stroke within 1 year
- known intracranial neoplasm
- active internal bleed
- suspected aortic dissection
- relative contraindications
- blood pressure > 180/110
- current anticoagulation therapy (warfarin)
- recent trauma (surgery, head, CPR)
- active peptic ulcer disease
- NO IM injections
- prior ischemic stroke & diabetes appear not to be contraindications[13]
- some patients on warfarin (INR < 1.8) may safely receive r-tPA following ischemic stroke[14]
tPA is apparently safe if used in patients with stroke mimetic[11]
Dosage
- GUSTO accelerated dose for acute MI:
- arterial thrombus
- acute ischemic stroke:
- FIRST rule out hemorrhage
- 0.9 mg/kg IV (max 90 mg)
- NO aspirin or heparin with 1st 24 hours after tPA
- pulmonary emobolus
* Intravenous (IV) heparin should be used in conjunction with t-PA for the 1st 48 hours after thrombolysis. Heparin infusion is adjusted to achieve aPTT of 50-70 sec.
Pharmacokinetics
- thrombolytic & fibrinolytic activity is dose-dependent
- rapid onset of action
- metabolized by the liver
- excreted in the urine
- distribution phase is approximately 5 minutes
- 1/2life is approximately 26 mintues
Adverse effects
- bleeding[7]
- bruising
- cerebral bleeding (within 36 hours)[6]
- alteplase associated with higher mortality in 1st week after ischemic stroke, but lower mortality thereafter[19]
- hypotension
- allergic reactions
- muscle pain
- fever
- reperfusion arrhythmias
- nausea/vomiting
Mechanism of action
- relatively fibrin-selective plasminogen activator[4]
- minimizes systemic lytic states
More general terms
Additional terms
References
- ↑ Clinical Diagnosis and Management by Laboratory Methods, 18th ed, J.B. Henry (ed), W.B. Saunders, Philadelphia, PA, 1991 pg 739
- ↑ Baron M, Norman DG, Campbell ID. Protein modules. Trends Biochem Sci. 1991 Jan;16(1):13-7. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2053133
- ↑ Fibrinolysis, Thrombosis, & Hemostasis: Concepts, Perspectives, and Clinical Applications. S Sherry, Lea & Febiger, Philadelphia, 1992, pg 71
- ↑ 4.0 4.1 4.2 4.3 Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ 6.0 6.1 Ovbiagele B, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- ↑ 7.0 7.1 7.2 Brown DL, Barsan WG, Lisabeth LD, Gallery ME, Morgenstern LB. Survey of emergency physicians about recombinant tissue plasminogen activator for acute ischemic stroke. Ann Emerg Med. 2005 Jul;46(1):56-60. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15988427
- ↑ 8.0 8.1 National Institute of Neurological Disorders Stroke rt-PA Stroke Study Group. Recombinant tissue plasminogen activator for minor strokes: the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study experience. Ann Emerg Med. 2005 Sep;46(3):243-52. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16126134
- ↑ 9.0 9.1 Saqqur M et al. Symptomatic intracerebral hemorrhage and recanalization after IV rt-PA: A multicenter study. Neurology 2008 Oct 21; 71:1304. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18753474
Tanne D and Levine SR. Safer thrombolysis for acute ischemic stroke: Is early recanalization the key? Neurology 2008 Oct 21; 71:1300. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18936422 - ↑ 10.0 10.1 Prescriber's Letter 16(7): 2009 COMMENTARY: Expanding the Window for Administration of tPA in Ischemic Stroke GUIDELINES: Expansion of the Time Window for Treatment of Acute Ischemic Stroke with Intravenous Tissue Plasminogen Activator (AHA/ASA, 2009) GUIDELINES: Early Management of Adults with Ischemic Stroke (AHA/ASA, 2007) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250717&pb=PRL (subscription needed) http://www.prescribersletter.com
del Zoppo GJ et al. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator. Stroke. 2009 May 28. [Epub ahead of print] PMID: https://www.ncbi.nlm.nih.gov/pubmed/19478221 DOI:http://dx.doi.org/ 10.1161/STROKEAHA.109.192535.
Hacke W et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359:1317-29. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18815396
Saver JL et al Number needed to treat to benefit and to harm for intravenous tissue plasminogen activator therapy in the 3 to 4.5 hour window. Joint outcome table analysis of the ECASS 3 trial. Stroke. 2009 Jun 4. [Epub ahead of print] PMID: https://www.ncbi.nlm.nih.gov/pubmed/19498197 DOI:10.1161/STROKEAHA.108.543561.
Lansberg MG et al Treatment time-specific number needed to treat estimates for tissue plasminogen activator therapy in acute stroke based on shifts over the entire range of the modified Rankin Scale Stroke. 2009 Jun;40(6):2079-84. Epub 2009 Apr 16. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19372447
Lansberg MG et al Efficacy and Safety of Tissue Plasminogen Activator 3- to 4.5-Hours After Acute Ischemic Stroke. A Metaanalysis. Stroke. 2009 May 28. [Epub ahead of print] PMID: https://www.ncbi.nlm.nih.gov/pubmed/19478213 - ↑ 11.0 11.1 Chernyshev OY et al. Safety of tPA in stroke mimics and neuroimaging-negative cerebral ischemia. Neurology 2010 Apr 27; 74:1340
- ↑ 12.0 12.1 Lees KR et al. Time to treatment with intravenous alteplase and outcome in stroke: An updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010 May 15; 375:1695. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20472172
Saver JL and Levine SR. Alteplase for ischaemic stroke - Much sooner is much better. Lancet 2010 May 15; 375:1667. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20472152 - ↑ 13.0 13.1 Mishra NK et al. Thrombolysis outcomes in acute ischemic stroke patients with prior stroke and diabetes mellitus. Neurology 2011 Nov 22; 77:1866 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22094479
- ↑ 14.0 14.1 Xian Y et al Risks of Intracranial Hemorrhage Among Patients With Acute Ischemic Stroke Receiving Warfarin and Treated With Intravenous Tissue Plasminogen Activator JAMA. 2012;307(24):2600-2608 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22735429 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1199153
Alberts MJ Cerebral Hemorrhage, Warfarin, and Intravenous tPA: The Real Risk Is Not Treating JAMA. 2012;307(24):2637-2639 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22735434 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1199130 - ↑ Department of Veterans Affairs, VA National Formulary
- ↑ Activase; Note: Clinical information on Activase http://www.gene.com/gene/products/information/cardiovascular/activase/insert.jsp#pharmacology
Retavase; Note: Clinical information on Retavase http://www.retavase.com/pdf/Retavase_PI.pdf - ↑ 17.0 17.1 Sharifi M et al. Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" trial). Am J Cardiol 2013 Jan 15; 111:273. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23102885
- ↑ 18.0 18.1 18.2 Deprecated Reference
- ↑ 19.0 19.1 Berge E, Cohen G, Roaldsen MB et al. Effects of alteplase on survival after ischaemic stroke (IST-3): 3 year follow-up of a randomised, controlled, open-label trial. Lancet Neurol 2016 Sep; 15:1028. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27450474
- ↑ 20.0 20.1 Kam W, Holmes DN, Hernandez AF et al. Association of recent use of non-vitamin K antagonist oral anticoagulants with intracranial hemorrhage among patients with acute ischemic stroke treated with alteplase. JAMA 2022 Feb 22; 327:760-771. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35143601 PMCID: PMC8832308 (available on 2022-08-10) https://jamanetwork.com/journals/jama/fullarticle/2789099