Alteplase

50mg lyophilized powder (IV)

Emergency Medicine Executive Summary

(Summary Version, Updated August 2021)


Alteplase is a fibrin-specific Tissue Plasminogen Activator (fibrinolytic) is widely accepted for emergency revascularization in acute myocardial infarction (MI), high risk acute pulmonary embolism (PE), and acute ischemic stroke (AIS)(1, 2, 3). In emergency medicine it is also used in intermediate-high risk PE and cardiac arrest when there is a high suspicion of MI or PE as the cause, in both scenarios the decision should be taken cautiously and in very selected cases (2, 4, 10).

Always seriously consider the contraindications and balance the risk of intracranial and other major bleeding events versus the benefit of the therapy. Fibrinolysis is an intervention that should be decided -or at least supported- by a specialist (emergency medicine, neurologist, cardiologist, intensivist).

Dosing Summary

Acute Coronary Syndrome with ST elevation (<12 hours)

FDA approved.

Adult dose:

  • ≤67kg: 15mg bolus + 0.75mg/kg in next 30 min

  • >67kg: 15 mg bolus + 50 mg in 30 min + 35 mg in 60 min

Acute Ischemic Stroke (<4.5 hours)

FDA approved for <3 hours after symptom onset (1996), Universally accepted use in <4.5 hours.
Adult dose:

  • <100kg: 0.09mg/kg bolus + 0.81mg/kg 60min

  • >100kg: 9mg bolus + 81mg 60min

Pulmonary Embolism

FDA approved.

Adult dose:

  • Intermediate risk: 50mg in 2 hrs

  • High risk: 100mg in 2 hrs

  • Cardiac arrest: 50mg bolus + 50mg if no ROSC in 15 min

Contraindications to systemic fibrinolytic therapy

There isn't a definite and universally accepted list of contraindications, and it seems to be a tendency to become simpler over the years. Beware that references differ in some issues.

Absolute contraindications (1, 2, 3, 9)

  • Previous intracranial haemorrhage or stroke of unknown origin at any time

  • Ischemic stroke in the preceding 6 months

  • Central nervous system damage or neoplasms or arteriovenous malformation

  • Recent major trauma / surgery / head injury (within the preceding month)

  • Gastrointestinal bleeding within the past month

  • Known bleeding disorder (excluding menses)

  • Aortic dissection

  • Non-compressible punctures in the past 24 hours (e.g. liver biopsy, lumbar puncture)

  • Active internal bleeding

Relative contraindications (1, 2, 3, 9)

  • Transient ischemic attack in the preceding 6 months

  • Oral anticoagulant therapy

  • Pregnancy or within 1 week postpartum

  • Refractory hypertension (SBP >180mmHg and/or DBP >110 mmHg)

  • Advanced liver disease

  • Infective endocarditis

  • Active peptic ulcer

  • Prolonged or traumatic resuscitation

Adult Dose

  • Acute Coronary Syndrome with ST elevation (<12 hours)

FDA approval in 1987.

Relevant studies: GUSTO trial, 1993 (5).

Dose, accelerated scheme (6):

  • ≤67kg: 15mg bolus + 0.75mg/kg in first 30 min + 0.5mg/kg in next 60min

  • >67kg: 15 mg bolus + 50 mg in first 30 min + 35 mg in next 60 min

  • Acute Ischemic Stroke (<4.5 hours)

FDA approval for <3 hours after symptom onset in 1996 (15). Universally accepted use for <4.5 hours (3, 7).

Relevant studies: NINDS trial, 1995 (8). ECASS III trial, 2008 (9).

Dose (6):

  • <100kg: 0.09mg/kg bolus + 0.81mg/kg in 60min

  • >100kg: 9mg bolus + 81mg in 60min

  • Pulmonary Embolism

FDA approval in 2002 for high risk PE, but also for “PE obstructing blood flow to a lobe or multiple lung segments” which is controversial if it is not causing hemodynamic deterioration. Usage in intermediate-high risk PE has been questioned, studied schemes do not support fibrinolysis as a standard intervention; if considered, always decide under the supervision of a specialist, in this scenario Pulmonary Embolism Response Teams (PERTs) are recommended (2, 11, 12). For cardiac arrest it can be used in selected cases, with very limited available data (10).

Recommended review: European Society of Cardiology PE Guidelines, 2019 (2).

Dose (6, 2, 10)

  • PE-High risk: 100mg in 2 hrs

  • PE-Cardiac arrest: 50mg bolus + 50mg if no ROSC in 15 min

Pediatric Dose

Very limited data. Not approved by the FDA. No dosing established by manufacturer (6),

  • Acute ischemic stroke (13)

    • 0.09mg/kg bolus + 0.81mg/kg in 60min

  • Pulmonary embolism (14)

    • High Risk PE: 0.5 mg/kg/hour IV in 6 hours

References

  1. Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119-177. doi:10.1093/eurheartj/ehx393.
    Pubmed

  2. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603. doi:10.1093/eurheartj/ehz405.
    Pubmed

  3. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association [published correction appears in Stroke. 2018 Mar;49(3):e138] [published correction appears in Stroke. 2018 Apr 18;:]. Stroke. 2018;49(3):e46-e110. doi:10.1161/STR.0000000000000158.
    Pubmed

  4. Busse LW, Vourlekis JS. Submassive pulmonary embolism. Crit Care Clin. 2014;30(3):447-473. doi:10.1016/j.ccc.2014.03.006.
    Pubmed

  5. GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329(10):673-682. doi:10.1056/NEJM199309023291001.
    Pubmed

  6. NIH-NLM (National Institutes of Health National Library of Medicine). DailyMed. Label: Activase - alteplase kit. Updated in October 2020. Visited in July 2021.
    DailyMed

  7. Powers WJ. Acute Ischemic Stroke. N Engl J Med. 2020;383(3):252-260. doi:10.1056/NEJMcp1917030.
    Pubmed

  1. NINDS - National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333(24):1581-1587. doi:10.1056/NEJM199512143332401.
    Pubmed

  1. ECASS III - Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-1329. doi:10.1056/NEJMoa0804656.
    Pubmed

  2. Lavonas EJ, Drennan IR, Gabrielli A, et al. Part 10: Special Circumstances of Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care [published correction appears in Circulation. 2016 Aug 30;134(9):e122]. Circulation. 2015;132(18 Suppl 2):S501-S518. doi:10.1161/CIR.0000000000000264.
    Pubmed

  1. MOPETT - Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M; “MOPETT” Investigators. Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial). Am J Cardiol. 2013;111(2):273-277. doi:10.1016/j.amjcard.2012.09.027
    Pubmed

  2. Kiser TH, Burnham EL, Clark B, et al. Half-Dose Versus Full-Dose Alteplase for Treatment of Pulmonary Embolism. Crit Care Med. 2018;46(10):1617-1625. doi:10.1097/CCM.0000000000003288
    Pubmed

  3. Roach ES, Golomb MR, Adams R, et al. Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young [published correction appears in Stroke. 2009 Jan 1;40(1):e8-10]. Stroke. 2008;39(9):2644-2691. doi:10.1161/STROKEAHA.108.189696.
    Pubmed

  4. Monagle P, Chan AKC, Goldenberg NA, et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines [published correction appears in Chest. 2014 Dec;146(6):1694. Dosage error in article text] [published correction appears in Chest. 2014 Nov;146(5):1422]. Chest. 2012;141(2 Suppl):e737S-e801S. doi:10.1378/chest.11-2308.
    Pubmed

  5. US-FDA (United States Food and Drug Administration). Drug Approval Package: Alteplase. Company: Genentech. Application No.: 103172-Supplement 1055. Approval Date: 6/18/1996. Indication for Use: Management of acute ischemic stroke in adults, for improving neurological recovery, and reducing the incidence of disability. Visited in July 2021.
    US-FDA

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