Tissue plasminogen activator (tPA), also known as alteplase, is a powerful medication used to treat acute ischemic stroke by dissolving the blood clot blocking an artery in the brain. This action restores blood flow and reduces long-term disability. However, tPA is a potent thrombolytic agent that carries a significant risk of causing severe internal bleeding, most dangerously within the brain itself. Strict guidelines, or contraindications, exist to ensure the treatment is only administered when the potential benefit outweighs the risk of catastrophic hemorrhage.
Contraindications Based on Time Since Stroke Onset
The effectiveness and safety of tPA depend intensely on the time elapsed since the onset of stroke symptoms. The primary therapeutic window for tPA administration is within three hours of the patient’s last known normal state. Beyond this initial window, the oxygen-deprived brain tissue (infarct core) becomes increasingly fragile. Extending treatment up to four and a half hours after symptom onset is possible for select patients, but this extended window requires additional exclusion criteria. After the four-and-a-half-hour mark, the drug’s benefit diminishes rapidly, and the risk of symptomatic intracranial hemorrhage increases dramatically.
Patient History and Systemic Bleeding Risk Contraindications
A patient’s medical history often reveals conditions that elevate the risk of a severe bleed with tPA. A history of any prior intracranial hemorrhage (ICH) is a significant contraindication, indicating a pre-existing vulnerability in the brain’s blood vessels. Similarly, a previous ischemic stroke or significant head trauma within the preceding three months suggests a brain structure highly susceptible to bleeding.
Known vascular abnormalities, such as an intracranial arteriovenous malformation (AVM) or aneurysm, disqualify a patient because these weak points are prone to rupture under the influence of a thrombolytic. Recent major surgical procedures or serious trauma within the last 14 days also pose a contraindication, as tPA could re-open surgical sites or cause uncontrolled internal bleeding. Additionally, any significant gastrointestinal or genitourinary hemorrhage within the past 21 days is a serious concern for systemic bleeding risk.
Acute Physiological and Laboratory Value Contraindications
Several real-time physiological measurements and laboratory values must be assessed immediately before tPA administration. Sustained, severe hypertension is a major acute disqualifier, specifically a systolic blood pressure greater than 185 mmHg or a diastolic pressure above 110 mmHg. Uncontrolled high blood pressure increases shear stress on blood vessel walls, making them more likely to rupture when clotting ability is reduced by tPA.
Abnormal blood glucose levels also present a risk; a concentration below 50 mg/dL is a contraindication because it can mimic stroke symptoms and complicate diagnosis. Laboratory values reflecting the patient’s clotting ability are scrutinized, notably a platelet count less than 100,000/mm³. If the patient is taking warfarin, an International Normalized Ratio (INR) greater than 1.7 suggests the blood is too thin, significantly increasing the risk of hemorrhage.
Imaging Findings and Concurrent Medication Contraindications
Immediate diagnostic imaging, typically a non-contrast Computed Tomography (CT) scan, is required before administering tPA, as it reveals absolute contraindications. The most straightforward imaging contraindication is any evidence of existing intracranial hemorrhage on the scan, which immediately rules out tPA. Additionally, a CT scan showing extensive regions of hypoattenuation, indicating an already large, established area of infarction, is a contraindication.
Treating a largely dead area of the brain increases the likelihood of hemorrhagic transformation upon reperfusion. Concurrent use of certain blood-thinning medications is another major contraindication due to the additive effect on bleeding risk.
Patients who have recently taken a Direct Oral Anticoagulant (DOAC) like rivaroxaban or apixaban are excluded, especially if the timing of the last dose or renal function is uncertain. Similarly, if a patient received a therapeutic dose of unfractionated heparin within the past 48 hours and has an elevated activated partial thromboplastin time (aPTT), tPA is withheld.