Understanding tPA and Acute Ischemic Stroke
Tissue plasminogen activator (tPA), also known by the generic name alteplase, is a potent clot-busting medication for the emergency treatment of acute ischemic stroke. This type of stroke occurs when a blood clot blocks an artery supplying blood to the brain. TPA aims to dissolve the clot and restore blood flow to minimize brain damage, but it carries a significant risk of severe bleeding, particularly in the brain. Due to this risk, strict protocols and criteria are followed to determine patient eligibility.
Absolute Contraindications to tPA Administration
Certain conditions absolutely prevent tPA administration to avoid severe complications like catastrophic bleeding. A critical initial step is a brain CT scan to differentiate between an ischemic stroke (clot) and a hemorrhagic stroke (bleed). TPA is only for ischemic strokes; administering it during a brain hemorrhage would worsen bleeding and can be fatal.
Time Window Limitations
The timing of treatment is crucial. TPA's effectiveness is time-sensitive. TPA is typically given within 4.5 hours of symptom onset. Beyond this window, risks often outweigh benefits. For strokes where the onset time is unclear, tPA may be contraindicated, though advanced imaging might identify some patients who could still benefit.
Conditions Increasing Bleeding Risk
Any condition that increases bleeding risk is a major contraindication for tPA. These include a history of intracranial hemorrhage, recent head trauma or stroke (within 3 months), or recent major surgery or internal bleeding within 21 days. Conditions affecting blood clotting, low platelet counts, or active use of blood thinners like warfarin (with elevated INR) or certain direct oral anticoagulants also make tPA unsafe.
Other Absolute Exclusions
High blood pressure upon hospital arrival (systolic > 185 mmHg or diastolic > 110 mmHg) is a contraindication. Other intracranial pathology like aneurysms, tumors, or arteriovenous malformations also prevent tPA use.
Relative Contraindications and Special Considerations
Relative contraindications require a careful risk-benefit assessment. These can include age over 80 with a history of stroke and diabetes for the 3- to 4.5-hour window, mild or rapidly improving symptoms, or a seizure at stroke onset. Extreme blood glucose levels must be managed before considering tPA. CT scans showing extensive infarction (more than one-third of a cerebral hemisphere) also increase bleeding risk after tPA, making it a contraindication. Patient or family refusal is also a factor.
Comparison of tPA vs. Alternatives
For patients who cannot receive tPA or have large vessel blockages, other treatments are available. The table below compares the main options for acute ischemic stroke.
| Feature | tPA (Alteplase) | Tenecteplase (TNK) | Mechanical Thrombectomy |
|---|---|---|---|
| Drug Class | Thrombolytic | Thrombolytic (engineered tPA) | Interventional Procedure |
| Administration | IV bolus followed by a 1-hour infusion | Single, simpler IV bolus | Catheter-based clot retrieval |
| Time Window | Typically within 4.5 hours of symptom onset | Typically within 4.5 hours; potentially longer in some settings | Up to 24 hours in select patients with large vessel occlusion, based on imaging |
| Clot Efficacy | Can dissolve smaller, more accessible clots | Higher fibrin specificity, potentially better for some occlusions | Highly effective for large artery clots |
| Best For | Early-presenting patients with smaller clots | Growing evidence supports its use for many patients, potentially replacing alteplase | Patients with large vessel occlusions who meet specific imaging criteria |
Advancements in Stroke Treatment
Modern stroke care has brought new options for patients who are not eligible for tPA. Tenecteplase (TNK) is a modified tPA with a longer half-life, administered as a single IV bolus. Studies suggest it may be more effective and as safe as alteplase. Mechanical Thrombectomy uses a catheter to remove large clots, a significant advance for large vessel occlusions. It can be performed over a much longer time window than tPA and is sometimes used alongside thrombolytic therapy.
Conclusion
Deciding on tPA is a critical choice in emergency stroke treatment, guided by strict criteria balancing the benefits of restoring blood flow against the risks of bleeding. Factors like stroke type, time of onset, bleeding risk factors, and medical history all play a key role. For those ineligible for tPA, advancements like Tenecteplase and mechanical thrombectomy provide effective alternatives. Seeking immediate medical care at a stroke center is vital for a positive outcome, as time is the most crucial factor.
Visit the American Heart Association for more information on stroke and emergency care.
