What are the absolute and relative contraindications to thrombolysis in patients with massive (high‑risk) pulmonary embolism, and what alternative reperfusion options are recommended?

Thrombolysis Contraindications in Pulmonary Embolism

In high-risk pulmonary embolism with shock or persistent hypotension, only a handful of absolute contraindications remain—primarily active intracranial hemorrhage, hemorrhagic stroke at any time, and central nervous system malignancy—because the immediate mortality risk outweighs bleeding concerns, making most traditional absolute contraindications merely relative in this life-threatening context. 1, 2

Absolute Contraindications (Even in High-Risk PE)

The following contraindications remain absolute even during cardiac arrest or profound shock:

• Hemorrhagic stroke or stroke of unknown origin at any time 1, 2
• Active intracranial hemorrhage 2
• Central nervous system damage, injury, or active malignancy 1, 2
• Known active bleeding disorder or diathesis 1, 2

These represent the only true barriers to thrombolysis when a patient is dying from massive PE. 1

Contraindications That Become Relative in High-Risk PE

Critical distinction: In the setting of high-risk PE with cardiogenic shock, persistent hypotension, or cardiac arrest, the following shift from absolute to relative contraindications because survival benefit outweighs bleeding risk: 1, 2, 3

• Ischemic stroke within the preceding 6 months (absolute in stable patients, relative in shock) 1, 2
• Recent major trauma, surgery, or head injury within 3 weeks (absolute in stable patients, relative in shock) 1, 2
• Gastrointestinal bleeding within the past month (absolute in stable patients, relative in shock) 1, 2
• Traumatic cardiopulmonary resuscitation 1, 2

Standard Relative Contraindications

These are relative contraindications in all PE contexts:

• Transient ischemic attack in preceding 6 months 2
• Current oral anticoagulant therapy 2
• Pregnancy or within 1 week postpartum (though thrombolysis is appropriate for massive PE in pregnancy, it becomes absolute within 6 hours of delivery) 2
• Non-compressible vascular punctures 2
• Refractory hypertension (systolic BP >180 mmHg or diastolic >120 mmHg) 4, 2
• Advanced liver disease 2
• Infective endocarditis 2
• Active peptic ulcer disease 2
• Diabetic hemorrhagic retinopathy 4, 2

Risk Stratification Determines Contraindication Weight

The hemodynamic status fundamentally changes the risk-benefit calculation: 4

• High-risk PE (shock/persistent hypotension): Thrombolysis is first-line therapy with very few absolute contraindications; the survival benefit clearly outweighs bleeding risk (mortality reduction demonstrated in meta-analysis: OR 0.47) 4, 5
• Intermediate-risk PE (hemodynamically stable with RV dysfunction): Standard contraindications apply; thrombolysis reserved only for hemodynamic deterioration despite anticoagulation 4, 1
• Low-risk PE: Thrombolysis contraindicated regardless of contraindication profile due to unfavorable risk-benefit ratio (NNH for major bleeding = 27, NNT to prevent death = 125) 1, 6

Alternative Reperfusion Options When Thrombolysis Contraindicated

When absolute contraindications exist in high-risk PE:

First-Line Alternative: Surgical Embolectomy

• Surgical pulmonary embolectomy is the preferred therapy when thrombolysis is absolutely contraindicated or has failed in high-risk PE 4, 7, 5
• Modern surgical techniques have reduced mortality risk substantially 5
• Can be performed with normothermic cardiopulmonary bypass 1

Second-Line Alternative: Catheter-Based Thrombectomy

• Catheter-directed thrombectomy or thrombus fragmentation should be considered when surgical embolectomy is not immediately available or surgery carries prohibitive risk 4, 7
• Recommended specifically for high-risk PE patients with: (i) high bleeding risk, (ii) failed systemic thrombolysis, or (iii) shock likely to cause death within hours before thrombolysis can take effect 4, 7
• Evidence quality is lower than for surgical embolectomy 4

Critical Pitfalls to Avoid

• Do not withhold thrombolysis in high-risk PE based on relative contraindications alone—the mortality from untreated massive PE (>15% early mortality) exceeds bleeding risk in nearly all scenarios 4, 3
• Do not use thrombolysis in hemodynamically stable PE even with RV dysfunction, as major bleeding risk (5.9%) and intracranial hemorrhage risk (1.74%) outweigh mortality benefit 6
• Do not delay thrombolysis for angiographic confirmation in high-risk PE—this increases bleeding complications without improving outcomes 2
• Avoid aggressive fluid boluses in high-risk PE as they worsen right ventricular failure; use vasopressors instead 1
• Early administration is critical—delayed thrombolysis is associated with higher mortality and more bleeding complications 8

Practical Algorithm for Decision-Making

1. Confirm high-risk PE (shock with systolic BP <90 mmHg or persistent hypotension requiring vasopressors) 7
2. Screen for the four absolute contraindications (intracranial hemorrhage, hemorrhagic stroke history, CNS malignancy, active bleeding disorder) 1
3. If no absolute contraindications exist: Administer rtPA 50 mg IV bolus immediately during CPR or 100 mg over 2 hours if not in arrest 1
4. If absolute contraindications present: Activate surgical embolectomy team immediately; consider catheter thrombectomy if surgery unavailable 4, 7
5. Continue unfractionated heparin throughout (target aPTT 1.5-2.5× normal) 1