A stroke occurs when blood flow to a part of the brain is interrupted, leading to the death of brain cells. Ischemic stroke, caused by a blockage, accounts for the vast majority of cases. Since an ischemic stroke is caused by a blood clot, the primary goal of acute medical intervention is to dissolve that blockage and restore circulation. Tissue plasminogen activator (TPA) represents the most significant pharmacological treatment available for patients experiencing an acute ischemic event. This intravenous medication is a specialized protein designed to break apart the clot, but its use is governed by strict medical guidelines to maximize its benefit while minimizing serious risks.
Understanding TPA’s Function in Ischemic Stroke
TPA is classified as a thrombolytic agent, meaning its purpose is the dissolution of a blood clot. The specific medication used in stroke care is typically Alteplase, a recombinant form of the naturally occurring human protein tissue plasminogen activator. The drug works by targeting the structural mesh that holds a blood clot together.
A blood clot is primarily composed of fibrin, which forms a dense meshwork. TPA initiates a chain reaction by acting as a catalyst, converting the inactive protein plasminogen into its active form, plasmin. Plasmin is a potent enzyme that cleaves the peptide bonds within the fibrin mesh, effectively breaking down the clot’s structural support.
The dissolution of the blockage restores the flow of oxygenated blood, a process known as reperfusion. Restoring blood flow quickly can save the surrounding brain tissue, often referred to as the ischemic penumbra. By dissolving the clot, TPA aims to limit permanent neurological damage and improve the patient’s long-term recovery. The success of this treatment hinges entirely on the rapidity of administration after the stroke begins.
Strict Criteria for TPA Administration
TPA administration requires a rapid and rigorous screening process due to the inherent risks involved. Before the drug is given, medical teams must confirm the patient is experiencing an ischemic stroke, not a hemorrhagic stroke. This confirmation is achieved through an immediate non-contrast computed tomography (CT) scan of the brain to rule out bleeding.
The most time-sensitive factor is the therapeutic window, often summarized as “time is brain.” The drug must be administered within a short window from the last time the patient was known to be well and symptom-free. The standard time frame is within three hours of symptom onset, though this may be extended up to four and a half hours for select patients. This narrow window exists because the likelihood of success decreases over time, while the risk of causing bleeding increases as damaged tissue becomes more fragile. Every minute counts in the evaluation and administration process.
A variety of patient conditions serve as contraindications because they significantly increase the risk of a severe bleeding complication. These absolute contraindications must be ruled out before treatment.
Absolute Contraindications
- History of intracranial hemorrhage.
- Evidence of active internal bleeding.
- Recent major surgery or serious head trauma within the last 14 days.
- Low platelet count (below 100,000 per cubic millimeter).
- Current use of blood thinners resulting in an elevated clotting time (INR > 1.7).
A patient’s blood pressure must also be carefully managed and controlled before TPA can be safely administered. If the systolic blood pressure is above 185 millimeters of mercury (mmHg) or the diastolic pressure is above 110 mmHg, the drug cannot be given. This strict control is necessary because high pressure significantly increases the chance that the agent will cause a catastrophic bleed in the brain.
Managing Risks and Post-Treatment Monitoring
The primary and most serious risk of TPA is its potential to cause bleeding, specifically a symptomatic intracranial hemorrhage (sICH). This complication occurs when the drug causes a new bleed within the brain, potentially leading to rapid neurological decline and death. Although the risk of sICH is generally low, its severity necessitates intense vigilance.
The mechanism that dissolves the stroke clot can also disrupt the body’s entire clotting system. This systemic effect puts patients at risk for bleeding elsewhere, such as from the gastrointestinal tract or at insertion sites for needles or catheters.
Following the TPA infusion, the patient must be transferred to a specialized setting, such as a stroke unit or intensive care unit, for continuous observation. The monitoring protocol involves frequent neurological checks, often every 15 minutes for the first two hours, to quickly identify worsening symptoms. These checks look for signs like a sudden severe headache, a drop in consciousness, or acute changes in movement or sensation.
Strict blood pressure management continues for at least 24 hours after treatment. The goal is to maintain systolic blood pressure at or below 180 mmHg and diastolic pressure at or below 105 mmHg to minimize the risk of hemorrhagic conversion. If any signs of neurological decline are noted, the TPA infusion is immediately stopped, and an emergency CT scan is performed to check for a new hemorrhage.