What is the role of systemic thrombolysis in the management of pulmonary embolism?

In Medical Concepts by Ming LiLeave a Comment

A previously well 41-year-old woman on OCP presents to the emergency department with acute-onset tachycardia, dyspnea, and leg swelling. While awaiting imaging, she rapidly deteriorates and BP drops to 86/60 (triage BP 134/78). CT shows bilateral pulmonary emboli.

Risk Stratification

Pulmonary embolism (PE) is a cardiovascular emergency which can result in significant morbidity and mortality for patients.​1​ It is classified as high risk (formerly “massive”), intermediate (formerly “submassive”), or low risk. High-risk PE is defined by hemodynamic instability (i.e., persistent systolic blood pressure <90mmHg for >15 minutes, cardiac arrest, persistent bradycardia <40 bpm with signs and symptoms of shock, or shock requiring inotropic support).​2​

What does the evidence show?

For patients with acute high-risk PE and no other cause of hemodynamic instability, systemic thrombolysis is the standard of care as the mortality benefit and recurrence reduction outweigh the risks of bleeding.​3​ Thrombolytic agents activate plasminogen to form plasmin, which accelerates lysis of thromboemboli and relieves clot burden, thus improving pulmonary perfusion.​4,5​ The most well-studied regimen for patients with a pulse is full-dose systemic thrombolysis with alteplase 100mg IV over 2 hours, and clinical improvement is generally noted within the first hour of infusion.​5–7​ Due to the associated risk of major bleeding, including intracranial hemorrhage (ICH), recent evidence has emerged for reduced-dose, specifically half-dose regimens which demonstrated similar hemodynamic improvement and fewer bleeding events.​1,4,5,8​ In the presence of absolute contraindications, other options include reduced-dose thrombolysis, catheter-directed thrombolysis, and catheter or surgical embolectomy.​9​

For patients with low to intermittent risk PE, early therapeutic anticoagulation (low-molecular-weight heparin, unfractionated heparin, or direct oral anticoagulants) is the mainstay of therapy.​7,8​ Although reduced-dose thrombolytics can be considered for patients with intermediate-risk PEs with signs of acute decompensation and low bleeding risk, it is not routinely recommended as there is no definitive evidence showing benefit over anticoagulation alone in this group.​1,4,8,10​

What are contraindications to systemic thrombolysis?​5,7​

BleedingAge > 65 years
· Active bleedingPregnancy
· Known bleeding diathesisSevere uncontrolled hypertension (180/110mmHg)
· Known coagulopathyRecent surgery (<10 days)
· Suspected aortic dissectionCVA (>3 months)
Brain/spinal cord pathologyRecent internal bleeding (<4 weeks)
· Intracranial malignancy or vascular lesion (AVM)Oral anticoagulation
· History of ICH or hemorrhagic CVANon-compressible vascular punctures
· Ischemic CVA <3 months
· Recent intracranial/spinal surgery or trauma <2 months
· Recent head trauma with fracture or brain injury <3 weeks

What about bleeding risk?

In patients without absolute contraindications, the overall incidence of ICH after thrombolytic therapy is 0.9-3%.​5​ A reasonable validated point-of-care tool to help predict risk of ICH during thrombolysis for PE is the PE-CH score.​11​ Although this score may over-estimate bleeding risk as it attributed all bleeding events post-thrombolysis to the thrombolytic, it is useful in clinical decision-making for patients who have relative contraindications for thrombolytics but might benefit from thrombolysis and no alternative therapeutic options are available.

PE-CH Score
Risk factors for bleedingScores
Age >65 years1 point
Peripheral vascular disease1 point
Prior CVA with residual deficit5 points
Prior MI1 point
Risk of ICH
0 point1.20%
1 point1.90%
2 points2.40%
>=5 points17.80%

What if the patient bleeds?

During administration of thrombolysis, patients must be monitored closely for development of neurological signs, hemodynamic/clinical stability, and signs of bleeding. Minor bleeding, including bleeding at compressible sites or that is not hemodynamically significant, is common and generally NOT an indication to stop therapy.​9​ However, major bleeding (critical sites, not easily accessible, hemodynamically significant) is an indication for immediate discontinuation of infusion and treatment of bleeding.​9​

Case resolution

After administration of alteplase, patient’s BP stabilizes, hypoxia improves, and she is admitted to Internal Medicine for ongoing management.

Bottom line

Thrombolytic therapy in unstable patients with high-risk PE results in early hemodynamic improvement and is lifesaving compared to anticoagulation alone.

This article was edited by Evan Formosa and copy-edited by George Gainham.


  1. 1.
    Brandt K, McGinn K, Quedado J. Low-Dose Systemic Alteplase (tPA) for the Treatment of Pulmonary Embolism. Ann Pharmacother. 2015;49(7):818-824. doi:10.1177/1060028015579988
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    Jaff M, McMurtry M, Archer S, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123(16):1788-1830. doi:10.1161/CIR.0b013e318214914f
  3. 3.
    Quezada C, Bikdeli B, Barrios D, et al. Meta-Analysis of Prevalence and Short-Term Prognosis of Hemodynamically Unstable Patients With Symptomatic Acute Pulmonary Embolism. Am J Cardiol. 2019;123(4):684-689. doi:10.1016/j.amjcard.2018.11.009
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    Stewart L, Kline J. Fibrinolytics for the treatment of pulmonary embolism. Transl Res. 2020;225:82-94. doi:10.1016/j.trsl.2020.05.003
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    Piggott Z, Jelic T. Pulmonary embolism with cardiac arrest: a STEMI patient’s unexpected course. CJEM. 2018;20(S2):S31-S36. doi:10.1017/cem.2017.386
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    Kearon C, Akl E, Comerota A, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e419S-e496S. doi:10.1378/chest.11-2301
  7. 7.
    Submassive & Massive PE [Internet]. EmcProject. Internet Book of Critical Care. (IBCC). Published April 16, 2023. Accessed December 25, 2023. https://emcrit.org/ibcc/pe/
  8. 8.
    Moore C, McNamara K, Liu R. Challenges and Changes to the Management of Pulmonary Embolism in the Emergency Department. Clin Chest Med. 2018;39(3):539-547. doi:10.1016/j.ccm.2018.04.009
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    Lahouti S. Acute Pulmonary Embolism: Management of Massive and Submassive Pulmonary Embolism[Internet]. RECAPEM. Published October 6, 2021. Accessed December 25, 2023. https://recapem.com/acute-pulmonary-embolism-management-of-massive-and-submassive-pulmonary-embolism-2/
  10. 10.
    Nguyen P, Stevens H, Peter K, McFadyen J. Submassive Pulmonary Embolism: Current Perspectives and Future Directions. J Clin Med. 2021;10(15). doi:10.3390/jcm10153383
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    Chatterjee S, Weinberg I, Yeh R, et al. Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy Development of the PE-CH Score. Thromb Haemost. 2017;117(2):246-251. doi:10.1160/TH16-07-0588

Staff Commentary

Massive pulmonary embolism is probably more common than we think. For every ten patients diagnosed with a pulmonary embolism, one of them will be classified as massive. Knowing and understanding the indications, contraindications, risks, and benefits of this first line therapy – thrombolytics – is critical for the emergency physician. Those of us who work in large urban emergency departments or dedicated regional stroke or cardiac centres likely will have little experience with thrombolytics, i.e., your patient with a stroke is receiving thrombolytics ordered by the neurologist, and the patient with a ST-elevation myocardial infarction is being rushed to the cath lab. Consequently, it may feel a bit daunting to order and give this medication because you just have not seen the outcomes to expect. This article is an excellent summary to fill in that knowledge gap.

Dr Melody Ong
Melody Ong is an emergency physician practising at Trillium Health Partners in the Greater Toronto Area.

Ming Li

Dr. Ming Li is a Family Medicine resident at the University of Toronto with a keen interest in emergency medicine. She is involved in medical education through scholarly projects, clinical teaching/supervision, and mentorship. Outside of medicine, she enjoys camping, hiking, traveling, and binge-watching TV shows.