When should thrombolytics, such as Alteplase (tissue plasminogen activator), be administered to a patient with pulmonary embolism (PE)?

Thrombolytic Therapy in Pulmonary Embolism

Thrombolytic therapy should be administered immediately to patients with high-risk PE characterized by hypotension (systolic BP <90 mmHg) or cardiogenic shock, unless absolute contraindications exist. 1, 2

Risk Stratification for Thrombolytic Therapy

High-Risk PE (Massive PE) - Thrombolytics Indicated

• Defined by:
  • Systolic blood pressure <90 mmHg
  • Drop in systolic BP >40 mmHg for >15 minutes
  • Signs of cardiogenic shock
• Strong recommendation for systemic thrombolytic therapy 1, 2
• Mortality benefit clearly established in this population 2
• All physicians strongly favor thrombolytic therapy in this scenario 3

Intermediate-Risk PE (Submassive PE) - Thrombolytics Generally Not Recommended

• Defined by:
  • Normal blood pressure
  • Evidence of right ventricular dysfunction (RVD) by echocardiography
  • Elevated cardiac biomarkers (troponin, BNP)
• Anticoagulation alone is recommended over routine thrombolysis 2, 1
• Consider thrombolytics only if clinical deterioration occurs after starting anticoagulation 2, 4
• Benefit of thrombolysis in this group is less clear and not established in randomized studies 2

Low-Risk PE - Thrombolytics Contraindicated

• Defined by:
  • Normal blood pressure
  • No evidence of RVD
  • Normal cardiac biomarkers
• Thrombolytic therapy should not be given 2, 5
• Mortality is less than 5% with standard anticoagulation 2

Thrombolytic Administration Protocol

For High-Risk PE:

1. Confirm diagnosis rapidly (echocardiography or CT)
2. Assess for contraindications to thrombolysis
3. Administer systemic thrombolysis via peripheral vein 2:
   • Alteplase (rtPA): 100 mg over 2 hours (standard regimen) 2, 1
   • Alternative: 0.6 mg/kg over 15 minutes (maximum 50 mg) in patients with relative contraindications 2

Special Circumstances:

• For patients in cardiac arrest with suspected massive PE: Consider administering alteplase during CPR 6
• For patients with high bleeding risk or failed systemic thrombolysis: Consider catheter-directed thrombolysis or surgical embolectomy 2, 1

Contraindications to Thrombolytic Therapy

Absolute Contraindications:

• Recent intracranial hemorrhage
• Known structural cerebral vascular lesion
• Recent stroke
• Active internal bleeding

Relative Contraindications:

• Recent major surgery or trauma
• Recent gastrointestinal bleeding
• Uncontrolled hypertension
• Pregnancy
• Advanced age

Monitoring and Complications

Major Complications:

• Major bleeding: Increased risk (31 more per 1000 patients) 2
• Intracranial hemorrhage: Increased risk (7 more per 1000 patients) 2
• Allergic reactions (particularly with streptokinase) 2

Monitoring:

• Continuous hemodynamic monitoring
• Frequent neurological assessments
• Monitor for signs of bleeding
• Serial hemoglobin measurements

Alternative Approaches

1. Catheter-Directed Therapy:

   • Consider when:
     • High bleeding risk exists
     • Systemic thrombolysis has failed
     • Shock likely to cause death before systemic thrombolysis can take effect 2, 1
   • May have lower bleeding risk than systemic thrombolysis 1

2. Surgical Embolectomy:

   • Consider when:
     • Expertise is available
     • Contraindications to thrombolysis exist
     • Patient fails to respond to thrombolytic therapy within the first hour 2, 1

Clinical Pearls

• Time is critical - do not delay thrombolysis in high-risk PE patients 2
• Echocardiography should be used during cardiopulmonary arrest/instability if PE is suspected 6
• Pulmonary embolism response teams (PERTs) can facilitate rapid decision-making in complex cases 1
• IVC filters are not recommended as routine treatment in PE patients receiving anticoagulation 1
• In patients receiving thrombolysis, continue the same intensity and duration of anticoagulant therapy as in comparable patients who do not receive thrombolysis 2

By following this algorithm, clinicians can appropriately select patients who will benefit most from thrombolytic therapy while minimizing the risk of hemorrhagic complications.