A stroke occurs when blood flow to a part of the brain is interrupted, causing brain cells to die. The majority of strokes (about 87%) are ischemic, caused by a clot blocking a blood vessel in the brain. The less common type is a hemorrhagic stroke, involving bleeding into the brain tissue. Recombinant tissue plasminogen activator (r-tPA), also known as Alteplase or Tenecteplase, is the primary pharmacological approach for treating acute ischemic stroke. This thrombolytic agent dissolves the clot to restore blood flow. Because r-tPA acts as a blood thinner, its use requires a rapid, strict screening process to maximize benefit while minimizing complications.
The Critical Time Window for Treatment
The decision to administer r-tPA is governed by the principle of “Time is Brain,” reflecting the rapid and irreversible loss of brain tissue during an ischemic stroke. The standard treatment guideline for intravenous r-tPA begins with a narrow window of up to three hours from the time a patient was last known to be well. This initial timeframe is based on robust clinical trial data demonstrating clear benefit.
The treatment window can be extended to four and a half hours for specific, carefully selected patients who meet additional, less restrictive criteria. This extended period is based on major international studies that showed a measurable benefit. The urgency of this time constraint mandates a rapid diagnostic process upon arrival, often referred to as the door-to-needle time, which ideally should be under 60 minutes.
Essential Eligibility Requirements
Before r-tPA can be considered, a patient must meet criteria confirming the nature of their medical event. The initial step involves emergency imaging, typically a non-contrast Computed Tomography (CT) scan, to confirm the event is an ischemic stroke and not a hemorrhage. The imaging must show no evidence of bleeding and should not display signs of extensive, old damage from a prior stroke.
The patient must present with a measurable neurological deficit, which is often quantified using the National Institutes of Health Stroke Scale (NIHSS). This scale assesses the severity of the stroke, typically indicating a moderate-to-severe deficit. While patients with very mild symptoms are often excluded, treatment is still considered if the deficit is deemed “disabling,” meaning it significantly impacts function, such as severe aphasia or a complete visual field loss.
r-tPA is generally recommended for adults aged 18 and older. Patients older than 80 years may still be eligible, but they are subject to more stringent criteria, especially when considered for the extended four-and-a-half-hour treatment window. Furthermore, the patient or their legally authorized representative must be able to provide informed consent, acknowledging the risks and potential benefits of the therapy.
Absolute Contraindications and Safety Screening
A rigorous safety screening must occur to identify absolute contraindications that prohibit treatment. The most immediate concern is uncontrolled high blood pressure, which significantly increases the risk of brain hemorrhage after r-tPA administration. Before the drug can be given, the patient’s systolic blood pressure must be below 185 millimeters of mercury (mmHg) and the diastolic pressure must be below 110 mmHg, and it must be maintained below 180/105 mmHg for the first 24 hours afterward.
A major contraindication is any evidence of acute or prior bleeding in the brain found on the initial CT scan or a history of intracranial hemorrhage. Recent major surgery, severe head trauma within the preceding three months, or a recent ischemic stroke within the last three months also rule out the use of r-tPA. The medication is also contraindicated if the patient has active internal bleeding or a known bleeding disorder, such as a low platelet count or an elevated International Normalized Ratio (INR) from taking Warfarin. Current use of a non-vitamin K antagonist oral anticoagulant (DOAC) without a clear assessment of drug level is also typically a contraindication, as these medications compound the bleeding risk.
Understanding the Risks and Benefits
The fundamental trade-off in using r-tPA is balancing the potential for life-changing recovery against the danger of symptomatic intracranial hemorrhage (sICH). The drug works by dissolving the blood clot, restoring blood flow, and limiting permanent brain injury. This action leads to improved functional outcomes and reduced long-term disability.
The primary complication is bleeding within the brain, or sICH, which occurred in about 6.4% of patients treated with r-tPA in the pivotal clinical trials, compared to a much lower rate in patients who did not receive the drug. This hemorrhage can worsen the neurological deficit and increase mortality. However, for appropriately selected patients, the potential to avoid long-term disability is considered to outweigh the risk of bleeding. The strict eligibility and contraindication screening process is designed to identify the patients for whom this benefit-risk ratio is most favorable.