When tPA is Indicated for Acute Ischemic Stroke, Treatment Must Be Started Immediately
If tPA is indicated for acute ischemic stroke, treatment should be initiated as rapidly as possible, with a target door-to-needle time of ≤60 minutes, as the benefits of thrombolysis are highly time-dependent and delay directly reduces the likelihood of favorable outcomes. 1
Time-Based Treatment Algorithm
Within 0-3 Hours of Symptom Onset
- Administer IV tPA immediately (Grade 1A recommendation) 1
- This represents the strongest evidence window with greatest absolute benefit 1
- Dose: 0.9 mg/kg (maximum 90 mg total), with 10% given as IV bolus over 1 minute, followed by 90% infused over 60 minutes 2
Within 3-4.5 Hours of Symptom Onset
- Administer IV tPA (Grade 2C recommendation) 1
- While evidence is less robust than the 0-3 hour window, treatment remains beneficial 1
- Use the same dosing protocol as above 2
- Important caveat: There is a trend toward higher symptomatic intracranial hemorrhage (7.8% vs 3.8%) and mortality (28.4% vs 21.4%) in the 3-4.5 hour window compared to 0-3 hours 3
Beyond 4.5 Hours of Symptom Onset
- Do NOT administer IV tPA (Grade 1B recommendation against) 1, 4
- Instead, obtain CT angiography urgently to identify large vessel occlusion for potential mechanical thrombectomy 4
- Endovascular therapy may be considered up to 6 hours (or 6-12 hours in select patients with advanced imaging) 1
Critical Time Targets
The door-to-needle time should be ≤60 minutes from hospital arrival. 1, 5
- Patients treated within 60 minutes have lower in-hospital mortality (adjusted OR 0.78) and less symptomatic intracranial hemorrhage (4.7% vs 5.6%) compared to those treated after 60 minutes 5
- Time from CT completion to groin puncture (if endovascular therapy planned) should ideally be <60 minutes 1
- The absolute benefit of tPA is greatest when treatment is initiated earliest—every minute counts 2
Contraindications That Prevent Starting tPA
Patients on Direct Oral Anticoagulants (DOACs)
- Do NOT routinely administer tPA to patients on DOACs (apixaban, rivaroxaban, dabigatran, edoxaban) 1, 6
- Standard coagulation tests do not reliably measure DOAC levels 6
- Consider mechanical thrombectomy instead 1, 6
Other Key Contraindications
- Intracranial hemorrhage on CT imaging 1
- Active internal bleeding 7
- Recent surgery, obstetrical delivery, or biopsy within 48 hours 7
- Severe thrombocytopenia or other hemostatic defects 7
Post-tPA Management
Aspirin Timing
- Delay aspirin until 24 hours after tPA administration and after repeat CT excludes intracranial hemorrhage 1
- Then initiate aspirin 160-325 mg daily 1
For Patients NOT Receiving tPA
- Administer aspirin 160-325 mg immediately after CT excludes hemorrhage and dysphagia screening is passed 1
- This should occur within 48 hours of symptom onset 1
Common Pitfalls to Avoid
Do not delay tPA for "minor" stroke symptoms—minor strokes are eligible for treatment within the same time windows, and outcomes are improved with treatment 2
Do not withhold tPA based solely on age—while patients <75 years and those with NIHSS <20 have greatest potential benefit, older patients should not be automatically excluded 2
Do not use tPA beyond 4.5 hours—the ATLANTIS trial demonstrated no benefit and increased symptomatic ICH (7.0% vs 1.1%) and fatal ICH (3.0% vs 0.3%) when tPA was given between 3-5 hours 8
Do not perform excessive suction or use excessive pressure when administering tPA through catheters, as this can cause vascular damage or catheter rupture 7