Objective Severe pulmonary embolism (PE) has a high mortality rate, which can be lowered by thrombolytic therapy (TT). However, full-dose TT is associated with major complications, including life-threatening bleeding. The aim of this study was to explore the efficacy and safety of extended, low-dose administration of tissue plasminogen activator (tPA) on in-hospital mortality and outcomes in massive PE.
Methods This was a single-center, prospective cohort trial at a tertiary university hospital. A total of 37 consecutive patients with massive PE were included. A peripheral intravenous infusion was used to administer 25 mg of tPA over 6 hours. The primary endpoints were in-hospital mortality, major complications, pulmonary hypertension, and right ventricular dysfunction. The secondary endpoints were 6-month mortality and pulmonary hypertension and right ventricular dysfunction 6 months after the PE.
Results The mean age of the patients was 68.76±14.54 years. The mean pulmonary artery systolic pressure (PASP; 56.51±7.34 mmHg vs. 34.16±2.81 mmHg, P<0.001) and right/left ventricle diameter (1.37±0.12 vs. 0.99±0.12, P<0.001) decreased significantly after TT. Tricuspid annular plane systolic excursion (1.43±0.33 cm vs. 2.07±0.27 cm, P<0.001), myocardial performance index (0.47±0.08 vs. 0.55±0.07, P<0.001), and systolic wave prime (9.6±2.8 vs. 15.3±2.6) increased significantly after TT. No major bleeding or stroke was observed. There was one in-hospital death and two additional deaths within 6 months. No cases of pulmonary hypertension were identified during follow-up.
Conclusion The results of this pilot study suggest that an extended infusion of low-dose tPA is a safe and effective therapy in patients with massive PE. This protocol was also effective in decreasing PASP and restoring right ventricular function.
Citations
Citations to this article as recorded by
2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults Mark A. Creager, Geoffrey D. Barnes, Jay Giri, Debabrata Mukherjee, William Schuyler Jones, Allison E. Burnett, Teresa Carman, Ana I. Casanegra, Lana A. Castellucci, Sherrell M. Clark, Mary Cushman, Kerstin de Wit, Jennifer M. Eaves, Margaret C. Fang, Jos JACC.2026; 87(13): 1626. CrossRef
2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines Mark A. Creager, Geoffrey D. Barnes, Jay Giri, Debabrata Mukherjee, William Schuyler Jones, Allison E. Burnett, Teresa Carman, Ana I. Casanegra, Lana A. Castellucci, Sherrell M. Clark, Mary Cushman, Kerstin de Wit, Jennifer M. Eaves, Margaret C. Fang, Jos Circulation.2026;[Epub] CrossRef
Personalised viscoelastometry-guided systemic thrombolysis for high- and intermediate-high-risk acute pulmonary embolism in the ICU: a single-centre randomised controlled interventional feasibility trial András Kállai, Anna Párkányi, Máté Berczi, Dalma Skultéti, János Domonkos Stubnya, Hanna Dóra Szász, Gergely Szombath, Adrienne Fehér, Zsolt Dániel Iványi, János Gál, János Fazakas Intensive Care Medicine Experimental.2026;[Epub] CrossRef
Reduced-Dose Tenecteplase in High-Risk Pulmonary Embolism Jennifer Hammond, Dean Cataldo, Christopher Allison, Seth Kelly The Journal of Emergency Medicine.2025; 71: 67. CrossRef
Fibrinolytic uses in the emergency department: a narrative review Brit Long, William J. Brady, Michael Gottlieb The American Journal of Emergency Medicine.2025; 89: 85. CrossRef
Pulmonary Embolism: Unanswered Questions and Ongoing Evidence Gaps Omar Elmadhoun, Michael P. Merren, Patrick M. Wieruszewski, Juan G. Ripoll, Jeffrey Huang, Harish Ramakrishna Journal of Cardiothoracic and Vascular Anesthesia.2025; 39(9): 2498. CrossRef
Low-dose Systemic Tissue-type-plasminogen-activator Compared to Conventional Anti-coagulation for the Treatment of Intermediate-high Risk Pulmonary Embolism Alan De la Rosa, Adrian Rojas Murguia, Michael J. Brockman, Debabrata Mukherjee, Manu Rajachandran, Nils P. Nickel Cardiovascular & Hematological Disorders-Drug Targets.2025; 25(1): 46. CrossRef
Shock Index and Physiological Stress Index for reestratifying patients with intermediate-high risk pulmonary embolism Marcos Valiente Fernández, Amanda Lesmes González de Aledo, Francisco de Paula Delgado Moya, Isaías Martín Badía, Elena Álvaro Valiente, Nerea Blanco Otaegui, Pablo Risco Torres, Ignacio Saéz de la Fuente, Silvia Chacón Alves, Lidia Orejón García, María S Medicina Intensiva (English Edition).2024; 48(6): 309. CrossRef
Safety and Efficacy of Reduced-Dose Versus Full-Dose Alteplase for Acute Pulmonary Embolism: A Multicenter Observational Comparative Effectiveness Study* Roman Melamed, David M. Tierney, Ranran Xia, Caitlin S. Brown, Kristin C. Mara, Matthew Lillyblad, Abbey Sidebottom, Brandon M. Wiley, Ivan Khapov, Ognjen Gajic Critical Care Medicine.2024; 52(5): 729. CrossRef
Management of high-risk pulmonary embolism in the emergency department: A narrative review Samuel G. Rouleau, Scott D. Casey, Christopher Kabrhel, David R. Vinson, Brit Long The American Journal of Emergency Medicine.2024; 79: 1. CrossRef
Addressing the rising trend of high‐risk pulmonary embolism mortality: Clinical and research priorities Scott D. Casey, William B. Stubblefield, Dieuwke Luijten, Frederikus A. Klok, Lauren M. Westafer, David R. Vinson, Christopher Kabrhel Academic Emergency Medicine.2024; 31(3): 288. CrossRef
Shock Index and Physiological Stress Index for reestratifying patients with intermediate-high risk pulmonary embolism Marcos Valiente Fernández, Amanda Lesmes González de Aledo, Francisco de Paula Delgado Moya, Isaías Martín Badía, Elena Álvaro Valiente, Nerea Blanco Otaegui, Pablo Risco Torres, Ignacio Saéz de la Fuente, Silvia Chacón Alves, Lidia Orejón García, María S Medicina Intensiva.2024; 48(6): 309. CrossRef