What is the absolute contradiction to tissue plasminogen activator (tPA)?

From the Guidelines

The presence of intracranial hemorrhage is an absolute contraindication to administering IV thrombolytic therapy, such as tPA, due to the increased risk of symptomatic intracranial hemorrhage after infusion 1. When considering the administration of tPA, it is crucial to exclude the presence of intracranial hemorrhage through imaging, such as non-contrast computed tomography (NCCT) or magnetic resonance imaging (MRI) of the brain, to minimize the risk of bleeding complications 1. Key points to consider when evaluating patients for tPA administration include:

• The presence of intraparenchymal hemorrhage, which occurs in 15% of all strokes, requires careful evaluation to exclude underlying vascular malformations or aneurysms 1
• The use of MRI without and with contrast may be beneficial in assessing for underlying neoplastic or vascular masses, but its sensitivity may be limited in the acute phase due to mass effect from the hematoma and complex MRI signal of blood products 1
• The primary goal of imaging during the 0-hour to 4.5-hour time window is to exclude the presence of intracranial hemorrhage and assess the presence and extent of ischemic changes, with the presence of a large acute hypodensity on NCCT increasing the risk for hemorrhagic transformation after thrombolytic therapy 1 Overall, the decision to administer tPA should be made with caution, taking into account the potential benefits and risks, and careful consideration of the patient's individual clinical presentation and imaging findings 1.

From the FDA Drug Label

CONTRAINDICATIONS Cathflo Activase should not be administered to patients with known hypersensitivity to Alteplase or any component of the formulation (see DESCRIPTION). The FDA drug label does not answer the question.

From the Research

Absolute Contradiction to tPA

• The risk of intracranial hemorrhage (ICH) after tPA administration is a concern in acute ischemic stroke patients 2, 3, 4, 5, 6
• Studies have shown that the risk of ICH after tPA is low in children, with an estimated risk of 2.1% 2
• In adults, the risk of ICH after tPA is associated with higher age, higher stroke severity, and higher glucose levels 5
• The use of tPA in combination with mechanical thrombectomy does not increase the risk of ICH, and may even lead to better radiographic outcomes and functional outcomes 3
• The risk of ICH after tPA is not significantly increased in patients receiving warfarin, as long as their international normalized ratio (INR) is 1.7 or lower 6

Risk Factors for ICH after tPA

• Higher age 5
• Higher stroke severity 5
• Higher glucose levels 5
• Atrial fibrillation 5
• Congestive heart failure 5
• Renal impairment 5
• Previous antiplatelet agents 5
• Leukoaraiosis 5
• Visible acute cerebral ischemic lesion on pretreatment brain imaging 5

tPA Administration and Outcomes

• tPA administration within 4.5 hours after symptom onset is associated with low risk of ICH in children 2
• tPA administration in combination with mechanical thrombectomy leads to better radiographic outcomes and functional outcomes 3
• tPA administration in patients receiving warfarin is not associated with increased risk of ICH, as long as their INR is 1.7 or lower 6