What are the guidelines for scoring and administering thrombolytic therapy, such as intravenous recombinant tissue plasminogen activator (tPA), in patients with acute ischemic stroke?

Scoring and Administration of Thrombolytic Therapy for Acute Ischemic Stroke

Primary Treatment Algorithm

For acute ischemic stroke patients, administer IV recombinant tissue plasminogen activator (r-tPA) at 0.9 mg/kg (maximum 90 mg) if treatment can be initiated within 3 hours of clearly defined symptom onset, with weaker support for treatment between 3-4.5 hours. 1, 2

Time-Based Treatment Windows

0-3 Hours from Symptom Onset:

• Strongly recommend IV r-tPA (Grade 1A evidence) 1
• Patients treated within this window are at least 30% more likely to have minimal or no disability at 3 months 3
• This represents the highest quality evidence with 154 more favorable events per 1,000 patients treated 1

3-4.5 Hours from Symptom Onset:

• Suggest IV r-tPA (Grade 2C evidence) 1, 4
• Benefit is smaller than the 0-3 hour window: 69 more favorable events per 1,000 patients 1
• All surveyed stroke clinicians treat eligible patients in this timeframe despite absence of FDA approval 5

Beyond 4.5 Hours:

• Do NOT administer IV r-tPA (Grade 1B evidence) 1, 4
• Strong evidence of harm without benefit 4

Dosing Protocol

• IV r-tPA: 0.9 mg/kg (maximum dose 90 mg) 2
• Administer 10% as bolus over 1 minute, remainder over 60 minutes 3

Clinical Scoring and Patient Selection

Key Assessment Tools Referenced in Guidelines

National Institutes of Health Stroke Scale (NIHSS):

• Used to assess stroke severity and predict outcomes 1, 3
• Lower baseline NIHSS scores predict more favorable outcomes 6
• Most clinicians define "mild stroke" exclusions based on perceived disability rather than specific NIHSS thresholds (80% of surveyed clinicians) 5

Modified Rankin Scale (mRS):

• Primary outcome measure at 3 months 1, 3
• Score 0-1 indicates very favorable outcome 7, 6
• Score 0-2 indicates functional independence 6

Critical Inclusion Criteria

• Clearly defined symptom onset time within treatment window 1, 8
• CT scan showing no evidence of intracranial hemorrhage 2
• Age is NOT an absolute contraindication—97% of clinicians treat elderly patients irrespective of age 5
• Stroke severity is NOT an absolute contraindication—95% treat severe strokes irrespective of NIHSS 5

Critical Exclusion Criteria

• International normalized ratio (INR) >1.7 5
• Evidence of intracranial hemorrhage on imaging 2
• Systolic blood pressure exceeding 185 mm Hg (though 6.7% of clinicians violate this in practice) 6

Safety Profile and Hemorrhagic Risk

Symptomatic Intracerebral Hemorrhage Rates:

• 6.4% in the landmark NINDS trial 3
• 3.3% in the STARS real-world study 6
• 7.3% in the SITS-MOST phase 4 study 1
• 0.6% in placebo groups 3

Predictors of Favorable Outcome:

• Less severe baseline NIHSS score 6
• Absence of hypodensity >33% of middle cerebral artery territory on baseline CT 6
• Age ≤85 years 6
• Lower mean arterial pressure at baseline 6

Adjunctive Therapy

Early Aspirin (within 48 hours):

• Administer 160-325 mg aspirin within 48 hours of stroke onset (Grade 1A) 1, 2, 4
• Do NOT delay aspirin in patients outside the thrombolytic window 4
• Aspirin is preferred over therapeutic anticoagulation in acute stroke 1

VTE Prophylaxis for Patients with Restricted Mobility:

• Prophylactic-dose subcutaneous LMWH preferred over unfractionated heparin (Grade 2B) 1, 2, 4
• Alternative: intermittent pneumatic compression devices (Grade 2B) 1, 2
• Do NOT use elastic compression stockings 2

Common Pitfalls to Avoid

• Protocol violations occur in 32.6% of cases in real-world practice 6
• Most common violations: treating beyond 3 hours (13.4%), administering anticoagulants within 24 hours of tPA (9.3%), and treating despite elevated blood pressure (6.7%) 6
• Only 18% of clinicians strictly adhere to AHA guidelines for the 0-3 hour window, though this increases to 51% for the 3-4.5 hour window 5
• Do NOT delay treatment for difficult IV access—consider alternative access methods 9
• Establish IV access in the non-paretic arm when possible to preserve the affected limb for rehabilitation 9

Alternative Therapies Beyond Standard Window

Intraarterial r-tPA (6-hour window):

• For proximal cerebral artery occlusions in patients who don't meet IV r-tPA eligibility criteria (Grade 2C) 1, 4
• Initiated within 6 hours of symptom onset 4

Mechanical Thrombectomy:

• Guidelines suggest against routine use (Grade 2C) 1
• May be considered in carefully selected patients who value uncertain benefits over risks 1