Tissue Plasminogen Activator (TPA) is a time-sensitive medication used to treat acute ischemic stroke by dissolving the clot blocking blood flow to the brain. Strict screening criteria must be met before TPA administration to maximize benefit and minimize serious complications. A blood glucose measurement is one of the most immediate and critical tests performed upon a patient’s arrival. This test reveals metabolic conditions that either mimic a stroke or significantly increase the risk of a severe outcome following treatment. The glucose level determines whether the treatment can proceed immediately or if an intervention is required first.
The Lower Limit: Hypoglycemia as a Stroke Mimic
A blood glucose level that is too low is a clear contraindication for TPA administration until it is corrected. Generally, a glucose level below 50 mg/dL is considered an absolute exclusion criterion for thrombolytic therapy in the acute stroke setting. Some institutional protocols may use a slightly higher threshold, such as 60 mg/dL, for mandatory immediate treatment. The primary reason for this strict exclusion is that severe hypoglycemia creates symptoms virtually indistinguishable from an actual ischemic stroke, known as a “stroke mimic.”
The brain relies almost entirely on glucose for energy, and a significant drop in blood sugar impairs normal neurological function. This energy deprivation can manifest as focal neurological deficits, including slurred speech, confusion, weakness on one side of the body (hemiparesis), or even altered consciousness. Since these are the same signs that trigger a stroke alert, doctors must first confirm that the symptoms are not simply due to a lack of fuel.
Administering TPA to a patient whose symptoms are caused solely by low blood sugar needlessly exposes them to the drug’s most serious side effect: a high risk of bleeding in the brain. If the low glucose level is the true cause, simply administering intravenous glucose will resolve the neurological symptoms. This quick correction and subsequent resolution of symptoms confirms the metabolic cause, allowing the medical team to safely bypass the drug.
The Upper Limit: Hyperglycemia and Increased Bleeding Risk
Although severe hyperglycemia is not always an absolute contraindication, extremely high blood glucose levels cause concern and influence the decision to administer TPA. Previous guidelines listed glucose levels above 400 mg/dL as a contraindication, and while this has been softened, levels this high still require careful risk assessment. Even moderately elevated admission glucose levels, such as those above 180 mg/dL, are strongly associated with worse outcomes after stroke.
The concern with high glucose is twofold, involving both damage to the brain tissue and an increased risk of bleeding. High blood sugar in the setting of an ischemic event can increase the production of lactic acid in the damaged area, leading to a larger final area of dead brain tissue (infarct size). This metabolic stress worsens the overall extent of the brain injury.
In patients receiving TPA, hyperglycemia is directly linked to a higher risk of symptomatic intracranial hemorrhage (sICH), which is bleeding within the brain causing neurological deterioration. Clinical studies show that the risk of sICH increases significantly with higher admission glucose levels. This increased bleeding risk is thought to be related to the way high glucose levels compromise the integrity of the blood-brain barrier.
Because of these risks, if TPA is administered to a patient with elevated glucose, aggressive monitoring and management of blood sugar levels are required immediately following treatment. The goal is to maintain the patient’s glucose within a target range, typically between 140 and 180 mg/dL, to mitigate further injury and reduce the likelihood of a major hemorrhagic complication.