What are the absolute contraindications to tissue Plasminogen Activator (tPA) lysis?

From the Guidelines

Absolute contraindications to tissue Plasminogen Activator (tPA) lysis include significant head trauma or prior stroke in the previous 3 months, symptoms suggesting subarachnoid hemorrhage, arterial puncture at a noncompressible site in the previous 7 days, history of previous intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm, recent intracranial or intraspinal surgery, elevated blood pressure, active internal bleeding, acute bleeding diathesis, and several other conditions as outlined in the guidelines for the early management of patients with acute ischemic stroke 1. The guidelines for the early management of patients with acute ischemic stroke provide a comprehensive list of absolute contraindications to tPA lysis, which are crucial to consider in order to minimize the risk of potentially catastrophic bleeding complications, particularly intracranial hemorrhage. Some of the key absolute contraindications include:

• Significant head trauma or prior stroke in the previous 3 months
• Symptoms suggesting subarachnoid hemorrhage
• Arterial puncture at a noncompressible site in the previous 7 days
• History of previous intracranial hemorrhage
• Intracranial neoplasm, arteriovenous malformation, or aneurysm
• Recent intracranial or intraspinal surgery
• Elevated blood pressure (systolic >185 mm Hg or diastolic >110 mm Hg)
• Active internal bleeding
• Acute bleeding diathesis, including but not limited to platelet count <100,000/mm³
• Current use of anticoagulant with INR >1.7 or PT >15 seconds
• Current use of direct thrombin inhibitors or direct factor Xa inhibitors with elevated sensitive laboratory tests These contraindications are based on the increased risk of bleeding associated with tPA therapy, and it is essential to carefully evaluate each patient's individual risk factors before initiating treatment 1. In addition to these absolute contraindications, there are also relative contraindications to consider, which may require careful weighing of the potential benefits and risks of tPA therapy on a case-by-case basis 1. Overall, the decision to administer tPA should be made with caution and careful consideration of the potential risks and benefits, and should always be guided by the most up-to-date and evidence-based guidelines available 1.

From the FDA Drug Label

Cathflo Activase should not be administered to patients with known hypersensitivity to Alteplase or any component of the formulation The absolute contraindication to tPA lysis is a known hypersensitivity to Alteplase or any component of the formulation 2.

From the Research

Absolute Contraindications to tPA Lysis

The use of tissue Plasminogen Activator (tPA) for thrombolysis is a critical treatment approach in various medical conditions, including acute ischemic stroke and pulmonary embolism. However, its application is not without risks, and certain conditions are considered absolute contraindications to tPA lysis due to the potential for severe complications.

• Previous Intracranial Hemorrhage: A history of intracranial hemorrhage is a significant concern when considering tPA therapy, as it may indicate a heightened risk of recurrent bleeding 3, 4.
• Known Arteriovenous Malformation (AVM) or Aneurysm: Although some studies suggest that unruptured AVMs or aneurysms may not be absolute contraindications 5, 6, the presence of these conditions requires careful consideration due to the potential risk of hemorrhage.
• Active Bleeding or Bleeding Diathesis: Patients with active bleeding or a bleeding diathesis are at increased risk of exacerbating their condition with tPA therapy.
• Severe Uncontrolled Hypertension: High blood pressure that is not well-controlled can increase the risk of intracranial hemorrhage during tPA treatment.
• Ischemic Stroke within the Last 3 Months: Recent ischemic stroke may be a contraindication due to the potential for hemorrhagic transformation.
• Head Trauma or Stroke within the Last 3 Months: Recent head trauma or stroke increases the risk of complications with tPA therapy.
• Intracranial Tumors: The presence of intracranial tumors, especially those with a high risk of bleeding, is a contraindication to tPA lysis.
• Pregnancy or Postpartum State: The safety of tPA in pregnancy and the postpartum state is not well-established, making these conditions relative or absolute contraindications depending on the clinical scenario.
• Severe Liver Disease or Coagulopathy: Significant liver disease or coagulopathy can impair the body's ability to regulate bleeding and clotting, making tPA therapy risky.

Considerations for tPA Administration

Despite these contraindications, the decision to administer tPA should be individualized, taking into account the specific clinical scenario, the potential benefits of treatment, and the risks involved 5, 4. In some cases, the benefits of tPA therapy may outweigh the risks, particularly in life-threatening conditions like massive pulmonary embolism or acute ischemic stroke. The use of tranexamic acid as a potential reversal agent for tPA-induced hemorrhage has also been explored 7, offering a possible strategy to mitigate risks in selected patients.