What are the latest guidelines for intravenous (IV) thrombolysis, specifically the administration of alteplase (tissue plasminogen activator) in a patient presenting with acute ischemic stroke?

Guidelines for IV Thrombolysis in Acute Ischemic Stroke

Administer IV alteplase (0.9 mg/kg, maximum 90 mg) to all eligible patients with acute ischemic stroke presenting within 4.5 hours of symptom onset or last known well, with a target door-to-needle time under 60 minutes. 1, 2, 3

Time Windows and Eligibility

Standard 0-3 Hour Window

• All patients with measurable neurological deficit should receive IV alteplase within 3 hours of symptom onset, regardless of stroke severity or extent of early ischemic changes on imaging 1, 2, 3
• Even patients with extensive early ischemic changes (>1/3 MCA territory) can be treated within 3 hours 2, 3
• Patients with mild symptoms that are potentially disabling may be considered for treatment, though the risk-benefit ratio requires careful assessment 1

Extended 3-4.5 Hour Window

• Patients presenting between 3-4.5 hours should receive IV alteplase unless they meet specific exclusion criteria 1, 4
• Patients >80 years of age are safe to treat in this window and should not be excluded based on age alone 1, 2
• The following additional exclusions apply in the 3-4.5 hour window: NIHSS >25, history of both diabetes and prior stroke, or any oral anticoagulant use regardless of INR 1

Beyond 4.5 Hours (Wake-Up Stroke)

• For patients with unknown time of onset or wake-up stroke, IV alteplase can be administered if MRI demonstrates DWI-FLAIR mismatch 3
• This approach requires MRI capability and should be administered within 4.5 hours of stroke symptom recognition 3

Dosing and Administration Protocol

The standard dose is 0.9 mg/kg (maximum 90 mg total): give 10% as IV bolus over 1 minute, then infuse remaining 90% over 60 minutes 1, 3, 5

Critical Time Targets

• Door-to-needle time should be <60 minutes in 90% of patients 2, 3
• Median door-to-needle time should be 30 minutes 2, 3
• Only blood glucose measurement must precede alteplase initiation—do not delay for other laboratory tests 3

Blood Pressure Management

• BP must be lowered to <185/110 mmHg before initiating thrombolysis 2, 3, 5
• Monitor BP every 15 minutes during and for 2 hours after infusion, then every 30 minutes for 6 hours, then hourly until 24 hours 1
• If BP rises to >180/105 mmHg during or after treatment, increase monitoring frequency and administer antihypertensives 1

Absolute Contraindications

Do not administer IV alteplase if any of the following are present:

Hemorrhagic Conditions

• CT or MRI showing intracranial hemorrhage 2, 5
• History of intracranial hemorrhage 1, 2
• Subarachnoid hemorrhage 1
• Active internal bleeding 2, 5
• GI malignancy or GI bleeding within 21 days 1

Recent Procedures and Trauma

• Intracranial or intraspinal surgery within 3 months 1, 5
• Serious head trauma within 3 months 5

Coagulation Abnormalities

• Platelets <100,000/mm³ 1, 5
• INR >1.7 1, 5
• aPTT >40 seconds or PT >15 seconds 1
• Treatment dose of LMWH within 24 hours 1
• Direct oral anticoagulants (DOACs) within 48 hours unless appropriate laboratory tests (aPTT, INR, ecarin clotting time, thrombin time, or direct factor Xa activity assays) are normal 1

Vascular Conditions

• Infective endocarditis 1
• Known or suspected aortic arch dissection 1
• Intra-axial intracranial neoplasm 1

Metabolic

• Blood glucose <50 mg/dL 5

Relative Contraindications and Special Situations

Anticoagulation (Nuanced Approach Required)

• Warfarin use with INR ≤1.7 and PT <15 seconds: may treat 1
• DOACs: do not treat if taken within 48 hours unless specific coagulation assays are normal AND renal function is normal 1
• Glycoprotein IIb/IIIa inhibitors should not be given concurrently with alteplase 1

Recent Procedures

• Lumbar puncture within 7 days: may consider treatment 1
• Major surgery within 14 days: may consider if surgical hemorrhage risk is outweighed by stroke severity 1
• Major trauma within 14 days (not involving head): may carefully consider based on bleeding risk versus stroke severity 1
• Arterial puncture of noncompressible vessel within 7 days: uncertain safety 1

Vascular Abnormalities

• Extracranial cervical arterial dissection: reasonably safe to treat within 4.5 hours 1
• Intracranial arterial dissection: uncertain risk 1
• Unruptured intracranial aneureurysm <10 mm: reasonable to treat 1
• Giant unruptured aneureurysm (≥10 mm): uncertain risk 1
• Unruptured intracranial vascular malformation: may consider if severe deficits and high anticipated morbidity outweigh hemorrhage risk 1

Hemorrhagic Imaging Findings

• 1-10 cerebral microbleeds on prior MRI: may treat 5

• 10 cerebral microbleeds: uncertain but increased hemorrhage risk should be considered 5

Clinical Scenarios

• Seizure at stroke onset: treat if residual deficits are clearly from stroke, not postictal 1, 3, 5
• Preexisting disability (mRS ≥2): may treat but consider quality of life, social support, and patient/family preferences 1
• Preexisting dementia: may treat based on life expectancy and premorbid function 1
• Early improvement but still moderately impaired: reasonable to treat 1
• Menstruation without menorrhagia: treat (warn patient of increased menstrual flow) 1
• Diabetic hemorrhagic retinopathy: may treat, weighing visual loss risk against stroke benefit 5

Integration with Mechanical Thrombectomy

Eligible patients should receive IV alteplase even if mechanical thrombectomy is being considered 2, 3

Critical Workflow Points

• Do not observe for clinical response to alteplase before initiating thrombectomy evaluation—any delay worsens outcomes 2, 3
• Obtain CTA in patients with clinically suspected large vessel occlusion 2, 3
• Initiate both treatments in parallel when large vessel occlusion is suspected 3

Post-Administration Monitoring

Immediate Monitoring

• Admit to intensive care or stroke unit 1
• Neurological assessments every 15 minutes during and for 2 hours after infusion 1
• Continue assessments every 30 minutes for 6 hours, then hourly until 24 hours 1

Management of Complications

If severe headache, acute hypertension, nausea, vomiting, or neurological worsening occurs:

• Discontinue alteplase infusion immediately 1
• Obtain emergency head CT 1
• Administer cryoprecipitate 10 units over 10-30 minutes 1
• Give tranexamic acid 1000 mg IV over 10 minutes OR ε-aminocaproic acid 4-5 g over 1 hour 1
• Obtain urgent hematology and neurosurgery consultations 1

Follow-Up Imaging

• Obtain CT or MRI at 24 hours after alteplase before starting anticoagulants or antiplatelet agents 1

Critical Pitfalls to Avoid

• Never delay treatment for non-essential laboratory tests—only glucose is required before initiating alteplase 2, 3
• Never exclude patients >80 years in the 3-4.5 hour window—this is outdated practice 1, 2
• Never wait to assess alteplase response before initiating thrombectomy evaluation 2, 3
• Do not place nasogastric tubes, indwelling bladder catheters, or intra-arterial pressure catheters until absolutely necessary 1
• Do not use low-dose alteplase (0.6 mg/kg)—this was shown to be inferior to standard dosing in predominantly Asian populations 6