Who Is A Candidate for Thrombolytic Therapy?

Thrombolytic therapy is used only to treat an ischemic stroke in people who do not have other bleeding disorders, among other criteria.

A stroke is damage to the brain caused by interruption in the brain’s blood supply. Stroke is a medical emergency and one of the leading causes of death and adult disability.

The three primary types of strokes are:

• Hemorrhagic stroke: Caused by blood vessel rupture resulting in damage to brain tissue.
• Ischemic stroke: Caused by blood clot blocking a blood vessel and cutting off blood supply to a part of the brain.
• Transient ischemic attack (TIAs): Brief period of reduced blood supply that usually lasts just a few minutes and resolves on its own. TIAs are often a precursor for ischemic strokes.

Thrombolytic therapy is a treatment to break up the blood clot in the brain’s blood vessel which caused the ischemic stroke. An enzyme known as tissue plasminogen activator (tPA) is administered to dissolve the blood clot and restore normal blood flow to the brain.

A blood clot forms when fibrin, a protein in the blood, forms a mesh where blood platelets aggregate. The tissue plasminogen activator binds to the plasminogen enzyme on the blood clot to produce plasmin, which breaks up fibrin in clots and acts as an anticoagulant. 

Plasminogen and its activators are naturally occurring substances in the blood released by endothelial cells in damaged blood vessels. Recombinant tissue plasminogen activator (rtPA) is synthetically produced in the labs for use in thrombolytic therapy. It is used mainly for ischemic strokes; it is not used for hemorrhagic strokes.

The goal of early thrombolytic therapy is to salvage the brain cells (neurons) that have suffered only partial damage, and limit the injury to the brain. Thrombolytic therapy must be administered as early as possible after symptoms of an ischemic stroke to achieve maximum benefits.

After an ischemic stroke, neurons in the core ischemic region are likely to suffer irreversible damage that results in tissue death (infarction). The neurons in the rim surrounding the infarcted area, known as the penumbra, can remain viable for up to four hours. Restoring blood supply quickly to the penumbral region improves the chances of maximum functional recovery.

Education about ischemic strokes and thrombolytic therapy is essential, so that people recognize symptoms and reach the hospital at the earliest.

The four main symptoms of an acute ischemic stroke are:

• Sudden weakness or numbness on one side of the body
• Sudden loss or change of vision
• Sudden speech difficulty or language comprehension difficulty
• Sudden dizziness or gait difficulty

If the above symptoms persist for five minutes, the patient must be immediately taken to the emergency department, preferably by paramedics.

The American Heart Association/American Stroke Association (AHA/ASA) recommends the following eligibility criteria for administration of thrombolytic therapy within three hours after symptoms of ischemic stroke:

• Diagnosis of ischemic stroke causing measurable neurologic deficit
• Neurologic signs are not clearing spontaneously
• Neurologic signs are not minor and isolated
• Symptoms are not suggestive of subarachnoid (space around the brain) hemorrhage
• Onset of symptoms less than three hours before beginning treatment
• No head trauma or prior stroke in the past three months
• No heart attack (myocardial infarction) in the past three months
• No gastrointestinal or genitourinary hemorrhage in the past 21 days
• No arterial puncture in a noncompressible site during the past seven days
• No major surgery in the past 14 days
• No history of prior intracranial bleeding
• Systolic blood pressure under 185 mm Hg, and diastolic blood pressure under 110 mm Hg
• No evidence of acute trauma or bleeding
• Not taking an oral anticoagulant, or if so, the dose and type should be considered using established criteria when deciding on emergency thrombolytic therapy. 
• If a stroke patient has taken heparin within the last 48 hours, they need special considerations for thrombolytic therapy.
• Platelet count of more than 100,000/microliter
• Blood glucose greater than 50 mg/dL (2.7 mmol)
• No seizure with residual post-seizure impairments
• Computed tomography (CT) scan does not show evidence of tissue death in multiple brain lobes
• The patient and family understand the potential risks and benefits of therapy

Based on favorable results from clinical trials, the AHA/ASA have revised the window of thrombolytic therapy from three hours to 4.5 hours, however, the FDA hadn’t yet endorsed this recommendation as of September 2020.

The revised AHA/ASA guidelines recommend that an eligible patient as per above criteria can receive thrombolytic therapy in the 3 to 4.5-hour window, provided the patient: 

• Is below 80 years of age
• Is not taking oral anticoagulants
• Has a baseline National Institutes of Health Stroke Scale (NIHSS) score below 25
• Has no history of stroke and diabetes
• Has no imaging evidence of ischemic damage to more than one third of the middle cerebral artery area

Thrombolytic therapy is administered intravenously or intra-arterially depending on the location of the clot. Ideally, the medication must be administered as quickly as possible after patient admission. The important steps taken during a thrombolytic therapy include:

Before the procedure

• A brain CT scan or MRI to confirm ischemic stroke and rule out hemorrhagic stroke
• Physical and neurological examination of the patient
• Obtaining medical history of the patient to check the patient’s eligibility for thrombolytic therapy

After the procedure

• The patient is kept in the ICU or stroke unit with close monitoring of vital signs such as
  • Blood pressure
  • Heart rate
  • Oxygen saturation level
• No antiplatelet or anticoagulant therapy is administered for 24 hours after thrombolytic therapy
• If there is any evidence of intracerebral bleeding, a blood product known as cryoprecipitate is administered after performing emergency blood tests and CT scan
• A repeat CT scan or MRI is performed 24 hours after administration of thrombolytic therapy to check for any bleeding in the brain

After 24 hours of bedrest, initiation of functional therapies including:

• Physical
• Speech
• Occupational

Alteplase is the only FDA-approved tissue plasminogen activator for thrombolytic therapy, to be administered within three hours after onset of ischemic stroke symptoms. Thrombolytic therapy is approved only for patients who meet the eligibility criteria of the AHA/ASA guidelines.

The primary benefit of thrombolytic therapy is improved chances of functional recovery after a stroke by revitalizing the penumbral neurons. Earlier the therapy is initiated, higher the chances of recovering most of the functional abilities.

The major complication from thrombolytic therapy is intracerebral hemorrhage, which can further worsen the situation. The symptoms of intracerebral hemorrhage include:

• Acute hypertension
• Headache
• Nausea or vomiting
• Worsening of neurological functions

Other complications include:

• Allergic reactions
• Systemic hemorrhage
• Oozing from IV line and venous puncture sites
• Angioedema (swelling of tissue under the skin or mucous membrane)

Following is the approximate prognosis for ischemic stroke patients, based on patient data recorded three months after their thrombolytic stroke therapy:

• Fifty percent of patients are completely or almost completely independent in activities of daily living.
• Fifteen percent of patients are moderately dependent on others.
• Fifteen percent of patients are completely dependent on others.
• The mortality rate is 20%.