Contraindications for Thrombolysis

Absolute Contraindications

• The European Society of Cardiology recommends that thrombolytic therapy is contraindicated in patients with active internal bleeding, history of hemorrhagic stroke, recent cranial trauma or neoplasms, blood pressure >200/120 mmHg, and diabetic hemorrhagic retinopathy 1, 2
• Active internal bleeding is an absolute contraindication for thrombolytic therapy, as recommended by the European Society of Cardiology 1
• History of hemorrhagic stroke or stroke of unknown origin at any time is an absolute contraindication for thrombolytic therapy, according to the European Society of Cardiology 1, 2
• Ischemic stroke within the preceding 6 months is an absolute contraindication for thrombolytic therapy, as stated by the European Society of Cardiology 1, 2
• Central nervous system damage or neoplasms are absolute contraindications for thrombolytic therapy, as recommended by the European Society of Cardiology 1, 2
• Recent major trauma, surgery, or head injury (within preceding 3 weeks) is an absolute contraindication for thrombolytic therapy, according to the European Society of Cardiology 1, 2
• Gastrointestinal bleeding within the last month is an absolute contraindication for thrombolytic therapy, as stated by the European Society of Cardiology 1, 2
• Known active bleeding disorder is an absolute contraindication for thrombolytic therapy, as recommended by the European Society of Cardiology 1, 2
• Diabetic hemorrhagic retinopathy is an absolute contraindication for thrombolytic therapy, according to the American College of Cardiology 3, 4

Relative Contraindications

• Transient ischemic attack in preceding 6 months is a relative contraindication for thrombolytic therapy, as stated by the European Society of Cardiology 1, 2
• Current oral anticoagulant therapy is a relative contraindication for thrombolytic therapy, according to the European Society of Cardiology 1, 2
• Pregnancy or within 1 week postpartum is a relative contraindication for thrombolytic therapy, as recommended by the European Society of Cardiology and the American Heart Association 1, 2, 5
• Non-compressible vascular punctures are a relative contraindication for thrombolytic therapy, as stated by the European Society of Cardiology 1, 2
• Traumatic cardiopulmonary resuscitation is a relative contraindication for thrombolytic therapy, according to the European Society of Cardiology 1, 2
• Refractory hypertension (systolic blood pressure >180 mmHg) is a relative contraindication for thrombolytic therapy, as recommended by the European Society of Cardiology 1, 2
• Advanced liver disease is a relative contraindication for thrombolytic therapy, according to the European Society of Cardiology 1, 2
• Infective endocarditis is a relative contraindication for thrombolytic therapy, as stated by the European Society of Cardiology 1, 2
• Active peptic ulcer is a relative contraindication for thrombolytic therapy, according to the European Society of Cardiology 1, 2
• Recent (within 10 days) gastrointestinal bleeding is a relative contraindication for thrombolytic therapy, as recommended by the American College of Cardiology 3, 4
• Large thrombus in left atrium or on prosthesis is a relative contraindication for thrombolytic therapy, according to the American College of Cardiology 3, 4
• Known bleeding diathesis is a relative contraindication for thrombolytic therapy, as stated by the American College of Cardiology 3, 4
• Previous exposure to streptokinase or APSAC (contraindication to reuse any streptokinase-containing agent) is a relative contraindication for thrombolytic therapy, according to the American College of Cardiology 3, 4

Special Considerations

• Hyperglycemia (especially >8.4 mmol/L) increases risk of symptomatic intracranial hemorrhage, as stated by the American Heart Association 5
• Uncontrolled severe hypertension requires careful management before considering thrombolysis, according to the American College of Cardiology 3, 4
• In life-threatening situations such as high-risk pulmonary embolism with cardiogenic shock or persistent hypotension, some contraindications that would be considered absolute in other contexts might become relative, as recommended by the European Society of Cardiology 1, 2

Contraindications and Considerations for Thrombolysis

Absolute and Relative Contraindications

• The American College of Cardiology recommends that previous exposure to streptokinase or APSAC is a contraindication to reuse any streptokinase-containing agent, and uncontrolled severe hypertension is also a consideration 6
• The European Heart Journal suggests that in high-risk pulmonary embolism with cardiogenic shock or persistent hypotension, some absolute contraindications may be reconsidered as relative, requiring individual risk-benefit assessment 7

Special Considerations for High-Risk Patients

• For patients with high-risk PE and absolute contraindications to thrombolysis, the European Heart Journal recommends that surgical embolectomy is the preferred therapy 7
• If surgical embolectomy is not immediately available, the European Heart Journal suggests that catheter embolectomy or thrombus fragmentation may be considered as alternatives 7

Alternative Therapies

• For patients with prosthetic valve thrombosis and contraindications to thrombolysis, the American College of Cardiology recommends a combination of subcutaneous heparin and warfarin for approximately 3 months as an alternative approach to help dissolve moderate amounts of residual thrombosis 6

Contraindications for Thrombolysis in Pulmonary Embolism

Absolute Contraindications

• Hemorrhagic stroke or stroke of unknown origin at any time remains an absolute contraindication even in life-threatening PE 8
• Ischemic stroke within the preceding 6 months is considered an absolute contraindication 8
• Central nervous system damage or neoplasms are absolute contraindications 8
• Recent major trauma, surgery, or head injury within the preceding 3 weeks are absolute contraindications 8
• Gastrointestinal bleeding within the last month is an absolute contraindication 8
• Known active bleeding disorder is an absolute contraindication 8

Relative Contraindications

• Pregnancy or within 1 week postpartum are relative contraindications 8, 9
• Non-compressible vascular punctures are relative contraindications 8
• Traumatic cardiopulmonary resuscitation is a relative contraindication 8
• Refractory hypertension (systolic blood pressure >180 mmHg) is a relative contraindication 8
• Advanced liver disease is a relative contraindication 8
• Infective endocarditis is a relative contraindication 8
• Active peptic ulcer disease is a relative contraindication 8

Critical Context: High-Risk vs. Non-High-Risk PE

• In high-risk PE with shock or persistent hypotension, most contraindications become relative rather than absolute, and thrombolysis should be administered unless there is active bleeding or recent hemorrhagic stroke 8
• The survival benefit of thrombolysis in hemodynamically unstable patients outweighs most bleeding risks 10, 11
• Thrombolysis should be administered unless there are very few absolute contraindications (primarily active hemorrhage or recent hemorrhagic stroke) 12

Bleeding Risk Considerations

• Major bleeding occurs in approximately 13% of patients receiving thrombolysis, with intracranial or fatal hemorrhage in 1.8% 8
• Risk factors that increase bleeding complications include recent surgery (within 7 days), history of peptic ulcer disease or GI/urinary tract bleeding, platelet count <150 × 10⁹/L, invasive vascular procedures within 7 days, and prolonged cardiopulmonary resuscitation 8, 9

Alternative Strategies When Thrombolysis is Contraindicated

• Surgical pulmonary embolectomy is the preferred alternative when absolute contraindications exist in high-risk PE 12
• Catheter-based embolectomy or thrombus fragmentation may be considered if surgery is not immediately available 12

Important Caveats

• Recent thrombolysis is not a contraindication to surgical embolectomy if thrombolysis fails 8
• Angiographic confirmation is no longer required before thrombolysis and actually increases bleeding complications 10, 11
• In pregnancy, thrombolysis is appropriate for massive PE but contraindicated within 6 hours of delivery due to extreme bleeding risk 9

Thrombolysis and Alternative Reperfusion Strategies in High‑Risk Pulmonary Embolism

Relative Contraindications Specific to Hemodynamics

• Refractory hypertension (systolic > 180 mmHg or diastolic > 120 mmHg) is considered a relative contraindication to systemic thrombolysis in pulmonary embolism. 13
• Diabetic hemorrhagic retinopathy is listed as a relative contraindication to thrombolysis. 13

Risk Stratification and Thrombolysis Benefit

• In patients with high‑risk pulmonary embolism (defined by shock or persistent hypotension), systemic thrombolysis is first‑line therapy; meta‑analysis shows a mortality odds ratio of 0.47 favoring thrombolysis, indicating a clear survival benefit despite bleeding risk. 13
• For intermediate‑risk pulmonary embolism (hemodynamically stable with right‑ventricular dysfunction), standard contraindications apply and thrombolysis is reserved only for patients who deteriorate hemodynamically despite anticoagulation. 14

Alternative Reperfusion Options When Thrombolysis Is Contraindicated

• Surgical pulmonary embolectomy is the preferred alternative therapy when absolute contraindications to thrombolysis exist or when thrombolysis fails in high‑risk pulmonary embolism. 13
• Catheter‑directed thrombectomy or thrombus fragmentation is recommended for high‑risk pulmonary embolism patients who have a high bleeding risk, have failed systemic thrombolysis, or are expected to die from shock within hours before thrombolysis can act; this option is considered when surgical embolectomy is unavailable or carries prohibitive risk. Evidence quality for catheter‑based approaches is lower than for surgical embolectomy. 14

Clinical Pitfalls

• Relative contraindications alone should not preclude thrombolysis in high‑risk pulmonary embolism, because early mortality exceeds 15 % and outweighs the bleeding risk. 13

Systemic Thrombolysis for Pulmonary Embolism – Indications, Contraindications, and Dosing (ESC Guidelines)

1. Indications by Risk Category

• High‑risk (massive) PE – Systemic thrombolysis is recommended for any patient with shock or persistent hypotension (systolic BP < 90 mmHg for ≥15 min) unless an absolute contraindication exists. Class I, Level A【15】【16】【17】
• Intermediate‑risk (submassive) PE – Routine primary thrombolysis is not recommended in hemodynamically stable patients. Class III, Level A【15】【17】
• Rescue thrombolysis – In intermediate‑risk PE, thrombolysis becomes a Class I recommendation if the patient deteriorates hemodynamically despite anticoagulation. Level A【15】【17】
• Low‑risk PE – Thrombolysis is contraindicated; anticoagulation alone yields <5 % 30‑day mortality. Class III, Level A【15】【17】【18】

2. Definition of Risk Categories (ESC)

3. Evidence Supporting Thrombolysis

• Meta‑analysis of high‑risk PE shows a mortality odds ratio of 0.47 favoring thrombolysis despite increased bleeding risk. Level A【18】
• Small randomized trial (massive PE with cardiogenic shock): 0 % mortality with thrombolysis vs 100 % with heparin alone (4/4 vs 4/4). Level B【18】
• PEITHO trial (intermediate‑risk PE): Thrombolysis reduced hemodynamic decompensation but increased major bleeding (including 2 % intracranial hemorrhage) and did not lower 30‑day mortality. Class IIa, Level A【16】

4. Absolute Contraindications (remain true even in high‑risk PE)

• History of hemorrhagic stroke (any time)
• Ischemic stroke within the preceding 6 months
• Central nervous‑system neoplasm or structural damage
• Major trauma, surgery, or head injury within the preceding 3 weeks
• Active internal bleeding
• Known bleeding diathesis

All items are *Class III, Level A* contraindications.【16】

5. Relative Contraindications (to be weighed against >15 % mortality risk in shock)

• Transient ischemic attack within 6 months
• Current oral anticoagulation
• Pregnancy or ≤1 week postpartum
• Non‑compressible vascular puncture sites
• Traumatic cardiopulmonary resuscitation
• Refractory hypertension (SBP > 180 mmHg)
• Advanced liver disease
• Infective endocarditis
• Active peptic ulcer

These are *Class IIb, Level B* considerations.【16】

6. Recommended Alteplase Dosing Regimens

The 2‑hour regimen yields faster hemodynamic improvement than prolonged 12–24 h infusions.【18】【16】
Accelerated regimen shows lower major‑bleeding rates (≈11 %) versus 21–24 % with the standard regimen, though differences are not statistically significant.【18】

7. Practical Decision‑Making Algorithm (ESC)

Imaging confirmation is preferred but not mandatory in unstable patients; bedside echocardiography showing RV dysfunction plus high clinical probability suffices.【18】【19】

8. Critical Pitfalls to Avoid

• Do not delay thrombolysis for angiographic confirmation in unstable patients; bedside echo is adequate. Class I, Level A【18】【19】
• Do not withhold thrombolysis in high‑risk PE solely because of relative contraindications; mortality benefit outweighs bleeding risk. Class I, Level A【15】【17】
• Do not routinely thrombolyze intermediate‑risk PE; PEITHO data show no mortality benefit and higher bleeding. Class III, Level A【16】【15】【17】

All statements are derived from the European Society of Cardiology (ESC) Pulmonary Embolism Guidelines and reflect the cited evidence levels.