Alteplase, also known as rTPA or TPA is indicated for treatment of acute ischemic stroke, under a very specific protocol.

Step #1: Is patient eligible for treatment? [All 3 must be present]

• Must be >=18 years old
• Clinical diagnosis of ischemic stroke causing a measurable neurological deficit
• Time of symptom onset carefully established with onset of symptoms <180 minutes before start of alteplase infusion

Step #2: Review contraindications [if any are present, should not administer alteplase]

• Evidence of intracranial hemorrhage on pretreatment CT
• Clinical presentation suggestive of subarachnoid hemorrhage, even with normal CT
• Active internal bleeding
• Known bleeding diathesis, including but not limited to:
• Platelet count < 100,000/mm
• Patient has received heparin within 48 hours and has an elevated aPTT (greater than upper limit of normal for laboratory)
• Current use of oral anticoagulants (e.g., warfarin sodium) or recent use with an elevated prothrombin time > 15 seconds (INR>1.7)
• Within 3 months any intracranial surgery, serious head trauma, or previous stroke
• Uncontrolled hypertension at treatment time (SBP>185 or DBP>110 mmHg)
• History of intracranial hemorrhage
• Known arteriovenous malformation, intracranial neoplasm, or aneurysm

 Step #3: Review Warnings [These are not contraindications, but need to be weighed in the decision to administer alteplase or not]

• Only minor or rapidly improving stroke symptoms
• Blood glucose abnormal (<50 or >400 mg/dL)
• Hemorrhage from gastrointestinal or urinary tract within last 21 days
• Major surgery or serious trauma (excluding head trauma) in the previous 14 days
• Post myocardial infarction pericarditis
• Recent arterial puncture at a noncompressible site
• Recent lumbar puncture
• Seizure observed at the onset of stroke symptoms
• Severe neurologic deficit (NIH Stroke Score>22)
• Major signs of cerebral infarction on CT (edema, hypodensity, mass effect, midline shift)

Step #4: If alteplase infusion is selected

• 0.9 mg/kg (maximum of 90 mg) infused over 60 minutes with 10% of the total dose administered as an initial intravenous bolus over 1 minute

References

Genentech, Full Prescribing Information, Activase® (Alteplase). Available at http://www.gene.com/gene/products/information/cardiovascular/activase/insert.jsp (last accessed 20 May 2008)

Merino JG, et al. Physician Knowledge of the Benefits, Risks, and Contraindications of Tissue Plasminogen Activator for Acute Ischemic Stroke. Stroke. 2001;32:2008-9.

The Brain Attack Coalition. TPA Stroke Study Group Guidelines.  Available at http://www.stroke-site.org/guidelines/tpa_guidelines.html (last accessed 20 May 2008)