What are the indications and contraindications for thrombolytic (tissue plasminogen activator, tPA) therapy in acute ischemic stroke?

From the Guidelines

Thrombolytic therapy, specifically intravenous alteplase (tPA), is recommended for select patients with acute ischemic stroke within 4.5 hours of symptom onset.

Indications:

• Acute ischemic stroke diagnosed clinically and by imaging
• Age ≥ 18 years
• Symptom onset within 4.5 hours
• Significant neurological deficit

Contraindications:

• Intracranial hemorrhage on CT scan
• Systolic blood pressure > 185 mmHg or diastolic > 110 mmHg
• Blood glucose < 50 mg/dL or > 400 mg/dL
• Active internal bleeding
• Recent major surgery or trauma (within 14 days)
• Current use of anticoagulants with INR > 1.7 or PT > 15 seconds
• Platelet count < 100,000/mm³
• History of intracranial hemorrhage
• Acute pericarditis or subacute bacterial endocarditis The standard dose is 0.9 mg/kg (maximum 90 mg), with 10% given as a bolus and the remainder infused over 60 minutes, as recommended by the American Heart Association/American Stroke Association 1. Before administration, obtain a non-contrast head CT to rule out hemorrhage. Monitor blood pressure closely during and after infusion. Be prepared to manage potential complications, particularly symptomatic intracranial hemorrhage. Thrombolysis works by activating plasminogen to plasmin, which breaks down fibrin clots. The time-sensitive nature of the treatment is due to the progressive death of brain tissue in the ischemic penumbra surrounding the core infarct. According to the American College of Chest Physicians evidence-based clinical practice guidelines, IV recombinant tissue plasminogen activator (r-tPA) is recommended if treatment can be initiated within 3 hours (Grade 1A) or 4.5 hours (Grade 2C) of symptom onset 1. In patients with acute ischemic stroke, the use of intravenous rtPA is associated with improved outcomes for a broad spectrum of carefully selected patients who can be treated within 3 hours of onset of stroke, and its use is also beneficial when treated between 3 and 4.5 hours of the last known well time 1. The guidelines from the American Heart Association/American Stroke Association recommend intravenous administration of rtPA for treatment of patients with acute ischemic stroke, with a standard dose of 0.9 mg/kg (maximum 90 mg) over 60 minutes, and close monitoring for potential complications 1.

From the FDA Drug Label

CONTRAINDICATIONS Cathflo Activase should not be administered to patients with known hypersensitivity to Alteplase or any component of the formulation

The FDA drug label does not answer the question.

From the Research

Indications for Thrombolytic Therapy

• Thrombolytic therapy with tissue plasminogen activator (tPA) is indicated for acute ischemic stroke patients who can receive treatment within 3 to 4.5 hours of symptom onset 2, 3
• Patients with acute ischemic stroke who present within 90 minutes of symptom onset may experience improved neurological outcomes with tPA treatment 4
• The use of tPA has been shown to be safe and effective in selected patients up to 4.5 hours after symptom onset, increasing the proportion of patients eligible for treatment 2, 3

Contraindications for Thrombolytic Therapy

• While specific contraindications are not listed in the provided studies, the expansion of indications for tPA therapy suggests a re-evaluation of original contraindications 5
• The use of tPA in patients with certain conditions, such as those on non-vitamin K antagonist oral anticoagulants (NOACs), requires careful consideration and is an area of ongoing research 5

Time Window for Thrombolytic Therapy

• The standard time window for tPA administration is within 3 hours of symptom onset, but recent studies support the safety and efficacy of treatment up to 4.5 hours after symptom onset 2, 3
• The expanded time window has increased the proportion of patients eligible for tPA treatment, but the treatment must be administered as soon as possible after symptom onset 2, 3

Safety and Efficacy of Thrombolytic Therapy

• Studies have demonstrated the safety and efficacy of tPA treatment for acute ischemic stroke, with improved neurological outcomes and low rates of symptomatic intracranial hemorrhage (SICH) and mortality 4, 6, 3
• The use of tPA in routine clinical practice has been shown to have similar safety and efficacy outcomes in different settings, including developing countries 6