Thrombolytics for pulmonary embolism

(Redirected from Thrombolysis for PE)

Overview

  • For most hemodynamically stable patients, thrombolytic therapy is NOT indicated
  • Major controversy exists regarding thrombolytic therapy in submassive PE. [1][2][3] The mortality benefit may be greatest in patients with right ventricular dysfunction. [4]
  • Bleeding risk is increased with increasing age especially in the group ≥ 65 yo[5]
  • There is no evidence suggesting administering thrombolytics within a certain window of time improves outcomes [6]
  • There is no evidence suggesting administering thrombolytics empirically during cardiac arrest improves outcomes
    • In patients with PEA secondary to confirmed PE, administration of thrombolytics may be indicated[7]

Indications

  • Patients with massive PE (i.e. persistent hypotension SBP <90 for ≥15 mins or requiring inotropic support) and acceptable risk of bleeding complications[8]
  • Can be considered in initially hemodynamically stable patients (i.e. submassive PE) who acutely decompensate despite anticoagulation

Evaluation

  • See Pulmonary Embolism (PE)
  • Massive PE[9]
    • Acute with
      • Sustained hypotension (systolic blood pressure <90 mm Hg for at least 15 minutes or requiring inotropic support, not due to a cause other than PE, such as arrhythmia, hypovolemia, sepsis, or left ventricular [LV] dysfunction) - ACCP 2016
      • Other definitions include pulselessness or persistent profound bradycardia (heart rate <40 bpm with signs or symptoms of shock)
  • Submassive PE[10]
    • Acute without systemic hypotension (see above) but with either RV dysfunction or myocardial necrosis
      • RV dysfunction means the presence of at least 1 of the following:
        • RV dilation (apical 4-chamber RV diameter divided by LV diameter >0.9) or RV systolic dysfunction on echocardiography
        • RV dilation (4-chamber RV diameter divided by LV diameter >0.9) on CT
        • Elevation of BNP (>90 pg/mL)
        • Elevation of N-terminal pro-BNP (>500 pg/mL); or
      • Electrocardiographic changes (new complete or incomplete right bundle-branch block, anteroseptal ST elevation or depression, or anteroseptal T-wave inversion)
      • Myocardial necrosis is defined as either of the following:
        • Elevation of troponin I (>0.4 ng/mL) or
        • Elevation of troponin T (>0.1 ng/mL)

Contraindications

Absolute contraindications

Relative contraindications

Administration

  • Standard dose: Alteplase 100mg over 2 hours [11][12]
  • Alternative dose: Alteplase 50mg over 2 hours
    • Half-dose regimen can be considered in patients >65yo, higher bleeding risk, or submassive PE (see MOPETT trial)
  • Tenecteplase in at 50 mg bolus or 0.5 mg/kg bolus has been used for PEA arrest [13][14][15]
  • Systemic therapy is recommended over catheter-directed therapy

Related Instructions

  • Review contraindications
  • Several trials continued unfractionated heparin (UFH) to target aPTT 1.5-2.5x baseline during thrombolytic administration so this would be standard [16][17]
    • However, discontinuing anticoagulation can be considered while administering thrombolytics
  • Always obtain serial aPTT every 4 hours after completion of thrombolytic
    • If heparin was discontinued during thrombolysis, resume heparin without a loading dose when aPTT <2x upper limit of normal
  • Ongoing CPR from 2010 AHA Guidelines is not an absolute contraindication, and some studies suggest permitting 15 min of CPR to allow thrombolysis to work[18]

Complications

  • Major bleeding[19]
    • Major bleeding OR 2.73 (9.24% vs 3.42%) compared to anticoagulant alone
    • Intracranial hemorrhage OR 4.63 (1.46% vs 0.19%)
    • There was no statistically significant increase in major bleeding risk in patients 65yo or younger
  • No standard or evidence-based reversal regimen exists but general guidelines include: [20]
    • Supportive care (e.g. transfusion)
    • Cryoprecipitate (contains fibrinogen) 10 units or more to achieve fibrinogen level >150 mg/dL
    • TXA or aminocaproic acid are antifibrinolytics, but limited data
    • PCC or FFP can be considered, but generally as adjuncts to cryoprecipitate
    • Consider vitamin K
    • Platelets controversial (theoretical benefit, but a small study showed worsening ICH with platelets)
    • Consider neurosurgical intervention if large ICH is found on CT

See Also

EBQ:Thrombolysis in Pulmonary Embolism Metanalysis

External Links

References

  1. Elliott C. et al. Fibrinolysis of Pulmonary Emboli — Steer Closer to Scylla.
  2. Sharifi M et al. Moderate pulmonary embolism treated with thrombolysis (from the “MOPPETT trial). J Cardiol 2013; 111: 273-7
  3. Meyer G. Fibrinolysis for patients with intermediate-risk pulmonary embolism. NEJM 2014; 370(15): 1402-1411
  4. Chatterjee. S et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA 2014; 311(23):2414-21. PubMed ID: 24938564.
  5. EBQ:Thrombolysis_in_Pulmonary_Embolism_Metanalysis#Outcomes
  6. Daniels L et al. Relation of duration of symptoms with response to thrombolytic therapy in pulmonary embolism. Am J Cardiol. 1997 Jul 15;80(2):184-8
  7. 15. Sharifi M et al. Pulseless electrical activity in pulmonary embolism treated with thrombolysis (from the “PEAPETT” study). Am J Emerg Med. 2016 Oct;34(10):1963-1967. doi: 10.1016/j.ajem.2016.06.094
  8. ACCP 9th Edition of the Antithrombotic Therapy Guidelines: Kearon C et al. Antithrombotic therapy for VTE disease. Chest. 2012;141:e419s – e494s. doi: 10.1378/chest.11-2301.
  9. Circulation 2011;123:1788
  10. Circulation 2011;123:1788
  11. Martin C et al. Systemic thrombolysis for pulmonary embolism: a review. P T. 2016 Dec; 41(12):770-775.
  12. Kearon C et al. Antithrombotic therapy for VTE disease. Chest. 2016;149(2):315-352. doi: 10.1016/j.chest.2015.11026
  13. Fatovich D, Dobb G, Clugston R. A pilot randomised trial of thrombolysis in cardiac arrest (The TICA trial). Resuscitation. 2004;61(3):309-313.
  14. Bozeman W, Kleiner D, Ferguson K. Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions. Resuscitation. 2006;69(3):399-406.
  15. Böttiger B, Arntz H, Chamberlain D, et al. Thrombolysis during resuscitation for out-of-hospital cardiac arrest. N Engl J Med. 2008;359(25):2651-2662.
  16. Konstantinides S et al. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002 Oct 10;347(15):1143-50.
  17. Meyer G et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014 Apr 10;370(15):1402-11. doi: 10.1056/NEJMoa1302097.
  18. Hayes BD. What’s the Code Dose of tPA? Updated August 2016. https://www.aliem.com/2013/whats-code-dose-of-tpa/.
  19. Chatterjee S et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014 Jun 18;311(23):2414-21. doi: 10.1001/jama.2014.5990.
  20. Yaghi S, et al. Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplace in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the AHA/ASA. Stroke. 2017;48:e343–e361

Authors:

Ross Donaldson