Several conditions absolutely exclude a patient from receiving alteplase (also called tPA), the clot-dissolving drug used to treat acute ischemic stroke. The most critical exclusion is any sign of bleeding in the brain, but the full list includes blood pressure thresholds, clotting abnormalities, recent trauma, and structural brain problems. These exclusions exist because alteplase works by breaking down clots throughout the body, which dramatically increases the risk of dangerous bleeding in patients who already have vulnerable blood vessels or compromised clotting ability.
How Alteplase Works and Why Exclusions Matter
Alteplase dissolves blood clots by activating a natural enzyme that breaks down the protein mesh holding clots together. This is lifesaving when a clot blocks blood flow to the brain, but the same clot-dissolving action can trigger catastrophic bleeding in patients with certain pre-existing conditions. The protective barrier between the bloodstream and brain tissue can break down during a stroke, and reperfusion (restoring blood flow) after that barrier is compromised raises the risk of bleeding into brain tissue. That risk is even higher in patients who have had a previous stroke, because prior damage to this barrier means it can fail more quickly during a new event.
Active Bleeding in the Brain
The single most important exclusion is any evidence of intracranial hemorrhage on brain imaging. This is why a CT scan is always performed before alteplase is given. The exclusion covers every type of brain bleed: bleeding within the brain tissue itself, bleeding around the brain’s surface, bleeding into the fluid-filled spaces of the brain, and bleeding between the skull and brain membranes. A stroke that has already started converting from a clot-based blockage into a bleed also rules out treatment.
A history of intracranial hemorrhage at any point in a patient’s life is also an absolute contraindication, even if the previous bleed was years ago. Both AHA/ASA guidelines and the drug’s prescribing label treat this as a firm exclusion.
Blood Pressure Above Safe Limits
Blood pressure must be below 185/110 mmHg before alteplase can be administered. If systolic pressure exceeds 185 or diastolic pressure exceeds 110, the patient is excluded until those numbers can be brought down. The concern is straightforward: high pressure in already-damaged blood vessels significantly increases the chance that dissolving a clot will lead to a hemorrhage rather than a recovery.
Recent Head Trauma or Stroke
Significant head trauma or a prior stroke within the previous 3 months disqualifies a patient. Recent head injuries can create small areas of bleeding or vessel damage that aren’t visible on imaging but could worsen dramatically once clot-dissolving medication enters the system. A recent stroke means brain tissue and blood vessels are still healing, making them far more susceptible to bleeding during reperfusion.
Symptoms that suggest subarachnoid hemorrhage (a type of bleeding around the brain) also exclude treatment, even if imaging hasn’t confirmed it yet. An arterial puncture at a site that can’t be compressed to stop bleeding within the previous 7 days is another exclusion.
Clotting and Blood Disorders
Because alteplase impairs the body’s ability to form clots, patients who already have compromised clotting are at extreme risk. The specific thresholds that exclude a patient include:
- Platelet count below 100,000/mm³: Too few platelets means the body can’t form clots to stop bleeding once alteplase is on board.
- INR above 1.7 or PT above 15 seconds: These lab values indicate blood is already taking too long to clot, often due to anticoagulant medication like warfarin.
- Heparin use within 48 hours with an elevated clotting time (aPTT): Heparin thins the blood, and its effects combined with alteplase create unacceptable bleeding risk.
- Active bleeding disorder: Any condition causing active, abnormal bleeding elsewhere in the body is an exclusion.
Blood Thinners and Direct Oral Anticoagulants
Patients taking direct oral anticoagulants (sometimes called DOACs or NOACs) within the previous 48 hours are formally contraindicated from receiving alteplase. Some guidelines allow treatment if specific clotting tests come back normal or if the patient’s last dose was more than 48 hours ago with normal kidney function, but the evidence supporting this exception is considered weak. In practice, recent use of these blood thinners is treated as a serious barrier to treatment.
Structural Brain Abnormalities
The presence of an intracranial tumor, arteriovenous malformation (an abnormal tangle of blood vessels), or brain aneurysm excludes a patient from receiving alteplase. These conditions involve fragile, abnormal blood vessels that are prone to rupture. Introducing a powerful clot-dissolving drug into that environment creates a high probability of life-threatening hemorrhage. Recent intracranial or spinal surgery is excluded for similar reasons: surgical sites in the brain or spine involve healing tissue and vessels that could reopen.
Large Areas of Brain Damage on Imaging
If a CT scan shows early signs of tissue damage covering more than one-third of the affected brain hemisphere, alteplase is contraindicated. Extensive damage visible this early indicates that a large volume of brain tissue has already lost its blood supply for a prolonged period. The blood vessels in that region are likely too damaged to safely handle restored blood flow, and giving alteplase in this situation is more likely to cause a massive bleed than to salvage functional brain tissue.
Abnormal Blood Sugar Levels
Very low blood sugar (below 50 mg/dL) and very high blood sugar (above 400 mg/dL) can both mimic stroke symptoms, so they must be checked and corrected before treatment. These aren’t permanent exclusions: if stroke symptoms persist after blood sugar is normalized, the patient can still receive alteplase. The point is to make sure the symptoms are actually caused by a stroke and not by a metabolic problem that has a simpler fix.
Age, Pregnancy, and Other Considerations
Advanced age is not an absolute contraindication, but it is recognized as a factor that increases bleeding risk. Patients over 80 were originally excluded from the extended treatment window (3 to 4.5 hours after symptom onset), though current guidelines have softened this restriction based on accumulating evidence.
Pregnancy falls into a gray area. Alteplase is classified as a category C drug in pregnancy, meaning there isn’t enough human data to confirm its safety. It’s unknown whether it crosses the placenta or passes into breast milk. The decision to treat a pregnant patient involves weighing the severity of the stroke against the uncertain risks to the fetus, and it remains a case-by-case judgment rather than an automatic exclusion.
Pediatric use is similarly under-studied, with limited research available to guide treatment decisions in children.