What is the role of thrombolytics in Pulmonary Embolism (PE)?

From the Guidelines

Thrombolytics should be used in patients with high-risk pulmonary embolism (PE) with hemodynamic instability, as they lead to faster improvements in pulmonary obstruction, pulmonary artery pressure (PAP), and pulmonary vascular resistance (PVR), accompanied by a reduction in right ventricular (RV) dilation on echocardiography, as evidenced by the 2019 ESC guidelines 1. The benefits of thrombolytic therapy are most pronounced when treatment is initiated within 48 hours of symptom onset, but it can still be useful in patients who have had symptoms for 6-14 days.

• Key benefits of thrombolytic therapy include:
  • Faster improvements in pulmonary obstruction, PAP, and PVR
  • Reduction in RV dilation on echocardiography
  • Significant reduction in the combined outcome of mortality and recurrent PE, as shown in a meta-analysis of thrombolysis trials 1
• However, thrombolytic therapy is also associated with an increased risk of severe bleeding, including a 9.9% rate of severe bleeding and a 1.7% rate of intracranial hemorrhage, as reported in the same meta-analysis 1. In normotensive patients with intermediate-risk PE, defined as the presence of RV dysfunction and elevated troponin levels, the impact of thrombolytic treatment was investigated in the Pulmonary Embolism Thrombolysis (PEITHO) trial, which found that thrombolytic therapy was associated with a significant reduction in the risk of hemodynamic decompensation or collapse, but also an increased risk of severe extracranial and intracranial bleeding 1. The preferred agent for thrombolytic therapy is alteplase (tPA) administered as 100mg IV over 2 hours, with alternative regimens including reteplase (10 units IV given twice, 30 minutes apart) or tenecteplase (single weight-based IV bolus), although the specific regimen may vary depending on the clinical context and patient characteristics, as noted in the 2019 ESC guidelines 1.

From the FDA Drug Label

The use of thrombolytics can increase the risk of thrombo-embolic events in patients with high likelihood of left heart thrombus, such as patients with mitral stenosis or atrial fibrillation. Activase has not been shown to treat adequately underlying deep vein thrombosis in patients with PE Consider the possible risk of re-embolization due to the lysis of underlying deep venous thrombi in this setting.

The thrombolytic agent streptokinase (IV) may increase the risk of thrombo-embolic events in patients with a high likelihood of left heart thrombus. Additionally, it may not adequately treat underlying deep vein thrombosis in patients with pulmonary embolism (PE), and there is a possible risk of re-embolization due to the lysis of underlying deep venous thrombi in this setting 2. Key considerations for the use of thrombolytics in PE include:

• Risk of thrombo-embolic events
• Inadequate treatment of underlying deep vein thrombosis
• Possible risk of re-embolization It is essential to carefully weigh the risks and benefits of using thrombolytics in patients with PE.

From the Research

Thrombolitics in PE

• Thrombolytic therapy is used to treat acute pulmonary embolism (PE) and can be lifesaving, especially in cases of massive PE 3, 4, 5, 6, 7
• The goal of thrombolytic therapy is to accelerate the dissolution of blood clots in the lungs and improve patient outcomes 3
• However, thrombolytic therapy also carries a risk of significant bleeding complications, including major and minor hemorrhage 3, 4, 5, 7

Indications for Thrombolytic Therapy

• Massive acute pulmonary embolism is the clearest indication for thrombolytic therapy 3, 6, 7
• Submassive pulmonary embolism is a more controversial indication, and the decision to use thrombolytic therapy should be made on a case-by-case basis 3, 4, 5, 7
• Risk stratification is important in determining which patients are the most appropriate candidates for thrombolysis, with careful consideration of contraindications 3, 4, 7

Thrombolytic Agents

• Several thrombolytic agents are available, including streptokinase, urokinase, and tissue-type plasminogen activator (t-PA) 3
• t-PA is the most widely used agent due to its proven benefit and relatively short infusion time 3
• Newer, unapproved agents include tenecteplase and reteplase 3

Administration of Thrombolytic Therapy

• Thrombolytic agents can be administered intravenously or via a pulmonary artery catheter 3, 6
• The choice of administration route and dosing regimen should be individualized based on the patient's condition and risk factors 4, 7

Efficacy and Safety of Thrombolytic Therapy

• Thrombolytic therapy has been shown to reduce mortality and recurrence of PE, but may also increase the risk of major and minor bleeding complications 5, 7
• The benefits and risks of thrombolytic therapy should be carefully weighed in each patient, with consideration of individual risk factors and contraindications 4, 5, 7