From the Guidelines
Alteplase is contraindicated in patients with active internal bleeding, intracranial hemorrhage, suspected aortic dissection, recent intracranial or intraspinal surgery, recent head trauma with fracture or brain injury, and bleeding diathesis, as well as those with severe uncontrolled hypertension, or on anticoagulants with elevated INR, according to the most recent guidelines from 2018 1. The contraindications for alteplase (tissue plasminogen activator, tPA) can be categorized into absolute and relative contraindications. Absolute contraindications include:
- Active internal bleeding
- Intracranial hemorrhage
- Suspected aortic dissection
- Recent intracranial or intraspinal surgery
- Recent head trauma with fracture or brain injury
- Bleeding diathesis
- Arteriovenous malformation or aneurysm
- Severe uncontrolled hypertension
- Patients currently on anticoagulants with elevated INR Relative contraindications include:
- Major surgery within 14 days
- Recent gastrointestinal or urinary bleeding within 21 days
- Recent trauma
- Pregnancy
- Severe liver disease For acute ischemic stroke specifically, additional contraindications include:
- Stroke or serious head trauma within 3 months
- Symptoms suggesting subarachnoid hemorrhage
- Administration beyond the approved time window (typically 3-4.5 hours from symptom onset) These restrictions exist because alteplase is a thrombolytic that converts plasminogen to plasmin, dissolving clots but simultaneously increasing bleeding risk throughout the body, as noted in the 2018 guidelines 1. The risk-benefit assessment must be individualized, especially in cases with relative contraindications, as the potential benefit of reperfusion must be weighed against potentially life-threatening hemorrhagic complications, as discussed in the context of acute ischemic stroke management 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 contraindications for Alteplase are:
- Known hypersensitivity to Alteplase or any component of the formulation 2
From the Research
Contraindications for Alteplase
The following are contraindications for Alteplase (tissue plasminogen activator, tPA):
- Recent use of non-vitamin K antagonist oral anticoagulants (NOACs) is generally considered a contraindication, although a study found that use of NOACs within the preceding 7 days was not associated with a significantly increased risk of intracranial hemorrhage 3
- A history of cerebral hemorrhage is not an absolute contraindication, as tPA intravenous thrombolysis does not increase symptomatic intracerebral hemorrhage measurements and mortality rates in patients with a history of cerebral hemorrhage 4
- Other contraindications are not explicitly stated in the provided studies, but it is known that alteplase is recommended for ischemic stroke patients presenting within 4.5 hours, and current guidelines advise delaying antiplatelet therapy for 24 hours after alteplase due to bleeding risks 5
Bleeding Risks
Bleeding risks associated with Alteplase include:
- Symptomatic intracranial hemorrhage, which occurred in 2.4% of patients treated with alteplase in one study 6
- Gastrointestinal bleeding, which was noted as a potential adverse reaction in another study 7
- Other bleeding events, such as gingival bleeding, epistaxis, and hematuria, which were also noted as potential adverse reactions 7
Special Considerations
Special considerations for Alteplase include:
- Patients with acute ischemic stroke who are taking NOACs may not be at increased risk of intracranial hemorrhage, but this requires further study 3
- Patients with a history of cerebral hemorrhage may benefit from tPA intravenous thrombolysis, but this also requires further study 4
- Different doses of alteplase may have different effects on neurological function and living ability, and further study is needed to determine the safety of low and standard doses of alteplase in patients with acute cerebral infarction 7