Contraindications for Thrombolysis
Thrombolytic therapy has specific absolute and relative contraindications that must be carefully evaluated, with the most critical absolute contraindications being hemorrhagic stroke at any time, active internal bleeding, recent major trauma/surgery within 3 weeks, and severe uncontrolled hypertension (>200/120 mmHg). 1
Absolute Contraindications
The following conditions represent absolute contraindications where thrombolysis should not be administered:
Neurological Contraindications
- Previous hemorrhagic stroke at any time or stroke of unknown origin 2, 1
- Ischemic stroke within the preceding 6 months 1
- Known intracranial neoplasm or central nervous system damage 2, 1
- Recent head trauma or cranial trauma within the preceding 3 weeks 1
Bleeding-Related Contraindications
- Active internal bleeding (excluding menses) 2, 1
- Gastrointestinal bleeding within the last month 1
- Known active bleeding disorder 1
Cardiovascular and Other Contraindications
- Suspected aortic dissection 2
- Blood pressure >200/120 mmHg despite treatment 1
- Recent major surgery within the preceding 3 weeks 1
- Diabetic hemorrhagic retinopathy 1
Relative Contraindications
These conditions require careful risk-benefit assessment but are not absolute prohibitions:
Cerebrovascular History
- Transient ischemic attack within the preceding 6 months 1
- History of prior cerebrovascular accident or known intracerebral pathology 2
Hypertension and Coagulation
- Severe uncontrolled hypertension on presentation (blood pressure >180/110 mmHg but <200/120 mmHg) 2, 1
- Current use of anticoagulants in therapeutic doses (INR >2-3) 2
- Known bleeding diathesis 2, 1
Recent Procedures and Trauma
- Recent trauma within 2-4 weeks, including traumatic CPR 2, 1
- Noncompressible vascular punctures 2, 1
- Recent internal bleeding within 2-4 weeks 2
Pregnancy and Other Conditions
- Pregnancy or within 1 week postpartum 1
- Active peptic ulcer disease 2, 1
- Advanced liver disease 1
- Infective endocarditis 1
- Large thrombus in left atrium or on prosthesis 1
Drug-Specific Contraindications
- Prior exposure to streptokinase/anistreplase (especially within 5 days to 2 years) or prior allergic reaction - this is a contraindication to reuse any streptokinase-containing agent 2, 1
Critical Context-Dependent Considerations
High-Risk Pulmonary Embolism Exception
In life-threatening situations such as high-risk pulmonary embolism with cardiogenic shock or persistent hypotension, most contraindications become relative rather than absolute. 1 In these scenarios:
- Thrombolysis should be administered unless there is active bleeding or recent hemorrhagic stroke 1
- The survival benefit outweighs most bleeding risks in hemodynamically unstable patients 1
- Surgical pulmonary embolectomy is the preferred alternative when absolute contraindications exist 1
Time-Dependent Efficacy
- Treatment within 3 hours of stroke onset shows greater benefit (OR 0.66 for reduced death or dependency) with no statistically significant increase in mortality 3
- Treatment beyond 4.5 hours increases mortality and reverses the risk-benefit balance 4
Risk Factors for Intracranial Hemorrhage
The following factors increase the risk of symptomatic intracranial hemorrhage (approximately 3% baseline risk):
- Advanced age (>65 years or >80 years) 2, 5
- Low body weight (<67-70 kg) - requires dose adjustment for alteplase 2
- Hypertension on admission 2
- Hyperglycemia, especially >8.4 mmol/L (>180 mg/dL) 1
- Severe baseline stroke (NIHSS >22) 5
- History of diabetes mellitus combined with prior stroke 5
Important Clinical Caveats
Dose Adjustments
- The dose of alteplase should be adjusted downward for patients weighing less than 67 kg (90-minute regimen) or 65 kg (180-minute regimen) to reduce intracranial hemorrhage risk 2
Reassuring Evidence for Common Clinical Situations
Recent comprehensive analysis demonstrates favorable outcomes with thrombolysis despite certain warnings in specific subgroups: patients aged >80 years (OR 1.40), those with combined history of prior stroke and diabetes (OR 1.50), patients on prior single antiplatelet agent (OR 1.42), and those with baseline glucose >180 mg/dL (OR 1.50) 5