How Tissue Plasminogen Activator (tPA) Works for Stroke

By
Jose Vega MD, PhD
jose vega, md, phd
Jose Vega MD, PhD
Jose Vega MD, PhD, is a board-certified neurologist and published researcher specializing in stroke.
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Updated on February 23, 2022
Medically reviewed
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 by
Nicholas R. Metrus, MD
Nicholas Metrus
Medically reviewed by Nicholas R. Metrus, MD

Nicholas R. Metrus, MD, is a board-certified neurologist and neuro-oncologist. He currently serves at the Glasser Brain Tumor Center in Summit, New Jersey.

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Tissue plasminogen activator, or tPA, is the only FDA-approved treatment for ischemic or thrombotic stroke, which is stroke caused by a blood clot interrupting blood flow to a region of the brain.

Medical team rushing down a hallway with a patient on a gurney
Chris Ryan / Getty Images

It has also been used in treatment for pulmonary embolism and myocardial infarction. TPA is a blood thinner, and therefore it is not used for hemorrhagic strokes or head trauma.

How It Works

TPA is a naturally occurring protein found on endothelial cells, the cells that line blood vessels. It activates the conversion of plasminogen to plasmin, an enzyme responsible for the breakdown of clots, helping restore blood flow to the brain. It is a powerful medication that must be administered by an experienced medical team.

Before tPA Treatment

Prior to receiving treatment with tPA, you should expect to have a brain computerized tomography (CT) scan. This is because there are several medical conditions that make it too dangerous for you to receive tPA. If you have any of these conditions, not only would tPA not help you, it could cause significant harm to your health.

Conditions that would make you ineligible to receive treatment with tPA include:

  • Hemorrhagic stroke (bleeding in the brain)
  • Brain aneurysm or AVM
  • Recent surgical procedure
  • Head injuries
  • Bleeding or blood clotting disorders
  • Bleeding ulcers
  • Pregnancy
  • Blood-thinning medication
  • Trauma
  • Uncontrolled high blood pressure

Administration of tPA

Treatment with tPA has been effective for people with an ischemic stroke as long as it is received intravenously within up to 4.5 hours of the onset of symptoms. Endovascular treatment to remove the clot or deliver tPA at the site of the clot is considered for up to 24 hours after a stroke.

Guidelines for the treatment of acute stroke published by the American Heart Association in 2018 strongly recommend IV alteplase (tPA) within 4.5 hours of stroke symptoms onset for eligible patients. This treatment approach has been shown to produce the best overall outcomes.

Protocols have been established to rapidly identify whether you could be having a stroke, so that your testing and treatment can be prompt and efficient, allowing you to receive life-saving treatments in a timely manner. In fact, some centers are making strides in diagnosing stroke sooner than ever before via mobile stroke units.

Side Effects

While tPA has been shown to be beneficial in the treatment of stroke, there is a risk associated with tPA treatment, even for people who have been medically cleared for tPA. It is a powerful blood thinner, and serious side effects may occur, including the following:

  • Hemorrhage (bleeding) affecting the brain: Causes headaches, weakness, confusion, loss of consciousness, seizures
  • Hemorrhage of the digestive system: Causes blood in the stool or stomach pain
  • Severe blood loss: Causes lightheadedness, low blood pressure, loss of consciousness
  • Minor bleeding in the gums or nose
  • Blood in the urine

If you experience any of these side effects, you should immediately inform your medical team.

Recognizing Symptoms of a Stroke

The best way to maximize your chances of receiving the most effective treatment for a stroke is to get to the emergency room as soon as possible. A person who is having a stroke may not notice when they are experiencing symptoms. You can learn how to recognize a stroke so that you can get immediate help.

Don’t wait for the symptoms to disappear. The sooner a stroke is treated, the fewer the long-term effects.

Symptoms of a stroke include:

  • Trouble understanding words or speaking
  • Numbness of the arm, face, or leg
  • Blurred or blackened vision in one or both eyes
  • Double vision
  • Sudden, severe headache
  • Vomiting
  • Dizziness
  • Difficulty walking
  • Loss of balance or coordination
  • Weakness of the face, arm, or leg
  • Droopy face or eyelid
  • Confusion

A Word From Verywell

Stroke prevention is a vital part of a healthy lifestyle. While treatments are becoming more effective for reducing the serious consequences of a stroke, prevention is the most effective way to avoid the consequences of stroke.

Ways to control risk factors for a stroke include:

  • Quitting smoking
  • Losing weight
  • Increasing physical activity
  • Reducing alcohol intake
  • Eliminating illegal drug usage
  • Lowering cholesterol and fat levels
  • Managing diabetes if you have it
  • Maintaining a healthy blood pressure

If you or a loved one has had a stroke or has received tPA for treatment of a stroke, expect a recovery that may take time.

Frequently Asked Questions

  • What is tPA used for?

    Tissue plasminogen Activator (tPA) is used to treat stroke in its early stages. The medication is a protein that activates enzymes to break down blood clots, helping to restore blood flow to the brain during an acute ischemic stroke. 

    IV administration of tPA is the gold-standard treatment for stroke. It helps to minimize brain damage but needs to be started within 4.5 hours of stroke onset.

  • What are the contraindications for tPA?

    Treatment with tPA is not right for everyone. It is approved for the treatment of stroke within 4.5 hours of stroke onset. There are several contraindications for tPA therapy. Some of these include:

    • Current use of certain anticoagulants, thrombin inhibitors, or direct factor Xa inhibitors
    • High blood pressure (above 185/110 mmHg)
    • Intracranial neoplasm, AVM, or an aneurysm
    • Low blood sugar (below 50 mg/dL)
    • Previous intracranial hemorrhage
    • Recent intracranial or intraspinal surgery
    • Significant head trauma or prior stroke in the last 3 months
    • Symptoms of a subarachnoid hemorrhage


  • Why is tPA not given after 4.5 hours?

    Research suggests tPA administered after 4.5 hours is not beneficial and may increase the risk of death. Some studies are investigating if tPA administration after 4.5 may provide benefits in certain situations.

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10 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

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