CardioNerds Drs. Dinu Balanescu, Billy-Joe Mullinax, and Mariana Garcia discuss systemic thrombolysis in pulmonary embolism with expert Dr. Allison Burnett. Audio editing by CardioNerds Academy intern, student doctor, Pace Wetstein.

Pulmonary embolism is the third leading cause of cardiovascular death in the US, and high-risk PE carries a 30-day mortality risk as high as 30-50%. In this episode, we discuss the indications for systemic thrombolysis, including high-risk PE and cardiac arrest. We addressed how to appropriately select candidates for systemic thrombolysis, balancing the high risk of bleeding. Additionally, we discussed anticoagulation management and timing concurrent with lytic therapy, as well as the importance of multidisciplinary PERT teams.

The 2026 American multi-society PE guidelines were published after this episode was recorded.

Dr. Dinu Balanescu and Dr. Billy-Joe Mullinax are Co-chairs for the CardioNerds PE Series, developed in collaboration with the PERT Consortium.

Enjoy this Circulation 2022 Paths to Discovery article to learn about the CardioNerds story, mission, and values.

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Pearls

Risk stratification is crucial in acute pulmonary embolism care. Based on the ESC 2019 guidelines, low-risk PE patients are those who are normotensive with no evidence of right ventricular dysfunction. Intermediate risk includes two categories: intermediate-low, with normotensive patients who have a high PE score with negative biomarkers, and intermediate-high risk, which has elevated biomarkers or signs of RV strain. High-risk PE includes hemodynamically unstable patients (SBP<90) who have end-organ dysfunction, shock, or cardiac arrest.
- The 2026 American multi-society PE guidelines presented a new clinical classification scheme is presented, entitled “Acute Pulmonary Embolism Clinical Categories,” with 5 categories (A-E) and subcategories, ranging from low to high risk for adverse outcomes.
Systemic lysis has been studied in patients at high and intermediate risk. Overall, the reduction in mortality has been seen in patients with high-risk PE.
Systemic thrombolysis is associated with high rates of bleeding, 2% fatal or high-risk intracranial hemorrhage per the PEITHO trial; therefore, selecting the appropriate population is critical to improve outcomes and balance the risks and benefits.
Multidisciplinary PERT teams are crucial for making high-quality decisions, and stewardship is necessary to optimize the care of patients with PE.

Notes

Notes: Notes drafted by Dr. Mariana Garcia-Arango

What is the role of systemic thrombolysis in the current era of available catheter-directed therapies?
- Thrombolytic therapy reduces mortality, PE recurrence, and PE-related mortality in patients with acute PE.
- The evidence supports use during high-risk PE and cardiac arrest.
- The clinical presentation is often severe, with high stakes and limited time to mobilize to the cath lab on time for catheter therapies, especially in rural populations.
How to approach the use of systemic thrombolysis during CPR?
- Cardiac arrest from PE carries a very poor outlook, with survival rates under 10%. Rapid, targeted interventions to restore circulation are critical.
- Systemic thrombolysis may be considered for patients in cardiac arrest due to confirmed or strongly suspected pulmonary embolism, especially when standard ACLS interventions have not been successful.
What is the best anticoagulation approach while using lytics?
- Most of the time, we should opt for low-molecular-weight heparin over unfractionated heparin, which has been shown to lead to less major bleeding and reduction of recurrent PE.
- Exceptions to the rule include renal dysfunction or if there is consideration of cannulation for ECMO or other invasive procedures.
- There is variation in practice regarding timing and initiation of anticoagulation while using lytics. There are different protocols given the variety of how studies were conducted.
- If they are going to get mechanical catheter-based therapy, the trend is to prefer LMWH.
- When lytics are included, either systemic or catheter-directed lytics, there is flexibility and room to discuss with the multidisciplinary PERT team which strategy to use.
- Future studies and trials are needed to standardize the best therapies.
What are the pharmacologic properties of available thrombolytics?
- Thrombolytics catalyze the conversion of plasminogen to plasmin, leading to fibrin degradation and thrombus dissolution.
- Alteplase is a recombinant tissue plasminogen activator, administered intravenously at a dose of IV 100 mg infusion over 2 hours. In cardiac arrest, the initial: 50 mg bolus over 2 minutes and continue CPR; after 15 minutes, if return of spontaneous circulation is not achieved and the medical team decides to continue CPR, repeat 50 mg bolus.
- Tenecteplase is a modified variant of alteplase with increased fibrin specificity. The usual dose is weight-based and delivered via IV bolus, which facilitates rapid delivery in emergency settings. Dose per weight: ≥60 to <70 kg: 35 mg, ≥70 to <80 kg: 40 mg, ≥80 to <90 kg: 45 mg, ≥90 kg: 50 mg
Are there any ongoing clinical trials and emerging therapies investigating novel thrombolytics and strategies to optimize efficacy while minimizing bleeding risk?
- PEITHO-3 is a large, randomized, double-blind, multinational study comparing reduced-dose intravenous alteplase with standard heparin in patients with intermediate-high-risk PE.

References

Sedhom R, Megaly M, Elbadawi A, et al. Contemporary national trends and outcomes of pulmonary embolism in the United States. Am J Cardiol. 2022;176:132-138. doi:10.1016/j.amjcard.2022.03.060
Marti C, John G, Konstantinides S, Combescure C, Sanchez O, Lankeit M, Meyer G, Perrier A. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. Eur Heart J. 2015 Mar 7;36(10):605-14. Epub 2014 Jun 10.
Zuo Z, Yue J, Dong BR, Wu T, Liu GJ, Hao Q. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev. 2021;CD004437.
Feltes J, Popova M, Hussein Y, Pierce A, Yamane D. Thrombolytics in cardiac arrest from pulmonary embolism: a systematic review and meta-analysis. J Intensive Care Med. 2023;39(5):477-483.
Javaudin F, Lascarrou JB, Le Bastard Q, Bourry Q, Latour C, De Carvalho H, Le Conte P, Escutnaire J, Hubert H, Montassier E, Leclère B; Research Group of the French National Out-of-Hospital Cardiac Arrest Registry (GR-RéAC). Thrombolysis during resuscitation for out-of-hospital cardiac arrest caused by pulmonary embolism increases 30-day survival: findings from the French National Cardiac Arrest Registry. Chest. 2019 Dec;156(6):1167-1175. Epub 2019 Aug 2.
Bonnard T, Tennant Z, Niego B, Kanojia R, Alt K, Jagdale S, Law LS, Rigby S, Medcalf RL, Peter K, Hagemeyer CE. Novel thrombolytic drug based on thrombin cleavable microplasminogen coupled to a single-chain antibody specific for activated GPIIb/IIIa. J Am Heart Assoc. 2017 Feb 3;6(2):e004535.
Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson ME, Wells PS, Gould MK, Dentali F, Crowther M, Kahn SR. 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 Feb;141(2 Suppl):e419S-e496S. Erratum in: Chest. 2012 Dec;142(6):1698-1704.
Levine M, Hirsh J, Weitz J, Cruickshank M, Neemeh J, Turpie AG, Gent M. A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism. Chest. 1990 Dec;98(6):1473-1479.
Rivera-Lebron B, Weinberg AS. Acute pulmonary embolism in adults: Reperfusion therapy in intermediate- and high-risk patients. In: Connor RF, ed. UpToDate. Waltham, MA: UpToDate Inc. Accessed August 28, 2025.

446. Pulmonary Embolism: Approach to Systemic Thrombolysis in Acute Pulmonary Embolism with Dr. Allison Burnett

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