What are the absolute contraindications for thrombolysis (using medications such as alteplase) in patients with acute ischemic stroke or other conditions?

Absolute Contraindications for Thrombolysis

The absolute contraindications for thrombolysis include any prior intracranial hemorrhage, ischemic stroke within 3-6 months, active internal bleeding, recent major surgery/trauma/head injury within 3 weeks, gastrointestinal bleeding within the last month, known bleeding disorders, central nervous system damage or neoplasms, and severe uncontrolled hypertension (>200/120 mmHg). 1, 2, 3

Core Absolute Contraindications

Hemorrhagic and Cerebrovascular Conditions

• Any history of hemorrhagic stroke or stroke of unknown origin at any time is an absolute contraindication across all clinical contexts 4, 1, 2, 3
• Ischemic stroke within the preceding 3-6 months (3 months for acute stroke protocols, 6 months for other indications like PE or MI) 4, 1, 2, 3
• Known structural cerebral vascular lesions including arteriovenous malformations and unruptured aneurysms 3
• Known malignant intracranial neoplasm or any central nervous system damage 4, 1, 3

Recent Trauma and Surgery

• Recent major trauma, surgery, or head injury within the preceding 3 weeks 4, 1, 2
• Intracranial or intraspinal surgery within 2 months 3
• Significant closed-head or facial trauma within 3 months 3

Active Bleeding and Coagulation

• Active internal bleeding (excluding menses) 1, 2, 3
• Gastrointestinal bleeding within the last month 4, 1, 2
• Known active bleeding disorder 4, 1, 2

Cardiovascular

• Suspected aortic dissection due to catastrophic risk of rupture 3

Blood Pressure

• Severe uncontrolled hypertension >200/120 mmHg despite emergency treatment 1, 2

Other Specific Contraindications

• Diabetic hemorrhagic retinopathy 1, 2
• Non-compressible vascular punctures within the past 24 hours 3

Relative Contraindications

Cerebrovascular

• Transient ischemic attack within the preceding 6 months 4, 1, 2

Cardiovascular and Hematologic

• Current oral anticoagulant therapy with therapeutic INR (>2-3) 4, 1, 2
• Known bleeding diathesis 1, 2
• Large thrombus in left atrium or on prosthetic valve 1, 2

Blood Pressure (Moderate Elevation)

• Hypertension 180-200/110-120 mmHg (between relative and absolute thresholds) 1, 2

Pregnancy and Recent Delivery

• Pregnancy or within 1 week postpartum 4, 1, 2
• Note: Alteplase does not cross the placenta, and limited evidence suggests it can be used safely in pregnancy for life-threatening conditions, though risks must be carefully weighed 4

Recent Procedures and Trauma

• Recent trauma within 2-4 weeks including traumatic CPR 1, 2
• Non-compressible vascular punctures 4, 1, 2

Medical Conditions

• Advanced liver disease 4, 1, 2
• Infective endocarditis 4, 1, 2
• Active peptic ulcer disease 4, 1, 2

Drug-Specific

• Prior exposure to streptokinase or APSAC (contraindication to reuse any streptokinase-containing agent, especially within 5 days to 2 years) 1, 2

Critical Context-Dependent Modifications

Life-Threatening Pulmonary Embolism Exception

In high-risk pulmonary embolism with cardiogenic shock or persistent hypotension, most contraindications become relative rather than absolute. 4, 1, 2

• The survival benefit of thrombolysis in hemodynamically unstable PE patients outweighs most bleeding risks 1, 2
• Even recent hemorrhagic stroke (typically absolute) may be reconsidered in truly life-threatening PE, though this requires individual risk-benefit assessment 4, 5, 6
• Surgical pulmonary embolectomy remains the preferred alternative when absolute contraindications exist 1
• If surgery is unavailable, catheter-based embolectomy or thrombus fragmentation may be considered 1

Ischemic Stroke Context

For acute ischemic stroke, absolute contraindications should be strictly observed and the context-dependent flexibility applied to PE does not apply 3

Risk Factors That Increase Intracranial Hemorrhage

While not contraindications, these factors significantly increase bleeding risk and require careful consideration:

• Advanced age (>65 years, especially >80 years) 2
• Low body weight (<67-70 kg) - requires dose adjustment for alteplase 2
• Hypertension on admission 2
• Hyperglycemia (especially >8.4 mmol/L or >180 mg/dL) 4, 2

Important Clinical Caveats

Bleeding Risk Data

• Major bleeding occurs in approximately 13% of patients receiving thrombolysis 4
• Intracranial or fatal hemorrhage occurs in 1.8% of patients 4
• Recent trials show lower bleeding rates when non-invasive imaging confirms diagnosis before treatment 4

Special Situations That Are NOT Absolute Contraindications

• Menstruation - can proceed with thrombolysis, though may require transfusion 4
• Cervical artery dissection - appears safe based on >50 reported cases without complications 4
• Cardiac thrombus - not an established contraindication but requires careful evaluation due to potential embolization risk 4
• Recent myocardial infarction - not included as contraindication in European guidelines, though pericarditis is contraindicated 4

Dosing Considerations

• Alteplase dose should be adjusted downward for patients weighing <67 kg to reduce intracranial hemorrhage risk 2
• For acute MI, aspirin 160-325 mg should be given as part of management 2

Timing

• For acute ischemic stroke, treatment within 3 hours is FDA-approved 7
• Extended window of 3-4.5 hours shows benefit (odds ratio 1.34 for favorable outcome) but with increased symptomatic intracranial hemorrhage (2.4% vs 0.2%) 8