From the Guidelines
TPA cannot be given to all stroke patients due to its limited time window, specific contraindications, and potential risks, including a 6-7% risk of symptomatic intracranial hemorrhage, as noted in the guidelines for the early management of patients with acute ischemic stroke 1. The primary concern is that TPA is only effective for ischemic strokes and must be administered within 4.5 hours of symptom onset for most patients.
- Key considerations include:
- The type of stroke: TPA is only suitable for ischemic strokes, not hemorrhagic strokes, as it can worsen bleeding in the latter case.
- Time window: The treatment must be initiated within 4.5 hours of symptom onset, with earlier treatment being more likely to result in a favorable outcome 1.
- Contraindications: These include recent major surgery, active internal bleeding, history of intracranial hemorrhage, current use of anticoagulants with elevated INR, platelet count below 100,000, blood pressure exceeding 185/110 mmHg despite treatment, blood glucose levels below 50 mg/dL, and seizures at stroke onset.
- The standard dose and administration protocol are crucial, with 0.9 mg/kg (maximum 90 mg) given as an initial bolus and the remainder infused over 60 minutes.
- A thorough assessment, including a CT scan to rule out hemorrhage and a review of the patient's medical history and current medications, is essential before administering TPA.
- The risk-benefit analysis is critical, weighing the potential benefits of TPA in reducing disability from ischemic stroke against its risks, such as symptomatic intracranial hemorrhage, as highlighted in guidelines for antithrombotic and thrombolytic therapy for ischemic stroke 1.
From the FDA Drug Label
The most frequent adverse reaction associated with all thrombolytics in all approved indications is bleeding Caution should be exercised with patients who have active internal bleeding or who have had any of the following within 48 hours: surgery, obstetrical delivery, percutaneous biopsy of viscera or deep tissues, or puncture of non‑compressible vessels Death and permanent disability have been reported in patients who have experienced stroke and other serious bleeding episodes when receiving pharmacologic doses of a thrombolytic
TPA (tissue plasminogen activator) cannot be given to all stroke patients because of the risk of bleeding. Patients with active internal bleeding, recent surgery, or other conditions that increase the risk of bleeding should be treated with caution. The risk of bleeding is a significant concern, and death and permanent disability have been reported in patients who have experienced stroke and other serious bleeding episodes when receiving pharmacologic doses of a thrombolytic 2.
From the Research
Reasons for Exclusion from tPA Therapy
- Delay in presentation to the emergency department beyond the recommended time frame for tPA administration, which is typically within 4.5 hours of stroke onset 3, 4
- Uncertain time of onset, patients waiting to see if symptoms would improve, delay caused by transfer from an outlying hospital, and inaccessibility of the treating hospital 4
- Mild stroke or clinical improvement, which may lead to perceived protocol exclusions 4, 5
- Significant comorbidity, such as atrial fibrillation, prosthetic heart valve, or diabetes mellitus 4, 5
- Use of anticoagulants, such as non-vitamin K antagonist oral anticoagulants (NOACs), which may increase the risk of bleeding complications 6
Patient and Hospital Characteristics Associated with Not Receiving tPA
- Older age, female sex, nonwhite race, and arrival at rural, nonteaching, non-stroke center hospitals located in the South or Midwest 5
- Longer onset-to-arrival and door-to-CT times, which may reduce the effectiveness of tPA therapy 5
- Arrival off-hours and not via emergency medical services, which may delay tPA administration 5
- Earlier calendar year, which may reflect improvements in tPA administration over time 5