What are the absolute and relative contraindications to intravenous thrombolysis with alteplase (tissue‑type plasminogen activator) in acute ischemic stroke patients?

Absolute and Relative Contraindications to Intravenous Thrombolysis in Acute Ischemic Stroke

Do not administer IV alteplase if any intracranial hemorrhage is present on CT/MRI, if the patient has a history of intracranial hemorrhage, or if blood pressure cannot be controlled below 185/110 mmHg despite aggressive treatment. 1, 2, 3

Absolute Contraindications

Hemorrhagic and Intracranial Conditions

• Any hemorrhage visible on brain imaging (CT or MRI) 1, 4
• Prior history of intracranial hemorrhage at any time 2, 3, 4
• Symptoms suggestive of subarachnoid hemorrhage 1, 4
• Known structural cerebral vascular lesions including unruptured aneurysms or arteriovenous malformations (though emerging evidence suggests these may be relative contraindications in select cases) 2
• Known malignant intracranial neoplasm 2

Recent Trauma and Surgery

• Stroke or serious head/spinal trauma in the preceding 3 months 1, 2, 4
• Major surgery (cardiac, thoracic, abdominal, orthopedic) in the preceding 14 days 1, 2
• Intracranial or intraspinal surgery within 2-3 months 2, 4
• Arterial puncture at a non-compressible site in the previous 7 days 1, 2

Active Bleeding

• Any source of active hemorrhage (excluding menstruation) 1, 2
• Gastrointestinal bleeding within the past 21-30 days 2, 4

Blood Pressure

• Hypertension refractory to aggressive treatment such that BP cannot be reduced below 185/110 mmHg 1, 3, 4
• Blood pressure must be treated rapidly and aggressively to minimize delays; failure to achieve target BP is the contraindication, not the initial elevated reading 1, 3

Laboratory Values

• Blood glucose below 2.7 mmol/L (50 mg/dL) 1, 4
• Blood glucose above 22.2 mmol/L 1
• Platelet count below 100,000/mm³ 1, 4
• International normalized ratio (INR) greater than 1.7 1, 4
• Elevated activated partial thromboplastin time (aPTT) 1, 4

Anticoagulation

• Patient currently prescribed and taking a direct oral anticoagulant (DOAC) within 48 hours unless specific coagulation assays are normal AND renal function is normal 1, 3, 4
• Heparin use within 48 hours with elevated aPTT 4

Imaging Findings

• CT showing early signs of extensive infarction (hypodensity >1/3 middle cerebral artery territory) 1, 4

Other Conditions

• Stroke symptoms due to non-ischemic acute neurological conditions such as seizure with post-ictal Todd's paralysis or focal signs from severe hypo/hyperglycemia 1

Relative Contraindications

The following conditions require careful risk-benefit assessment but are not absolute exclusions:

Cerebrovascular

• Transient ischemic attack within the preceding 6 months 2
• Ischemic stroke within 3 months (absolute in some guidelines, relative in others) 2

Cardiovascular

• Large thrombus in left atrium or on prosthetic valve 2
• Infective endocarditis 2

Coagulation (Borderline Values)

• Therapeutic anticoagulation with INR 1.7-2.0 (requires clinical judgment) 2
• Known bleeding diathesis 2

Blood Pressure (Moderate Elevation)

• Hypertension 180-200/110-120 mmHg that responds to treatment 2

Pregnancy and Postpartum

• Pregnancy or within 1 week postpartum 2
• However, alteplase does not cross the placenta, and limited evidence (approximately 30 cases, including 6 stroke patients) suggests it can be administered safely when benefits outweigh risks 1

Recent Procedures

• Recent trauma within 2-4 weeks 2
• Traumatic cardiopulmonary resuscitation 2
• Non-compressible vascular punctures 2

Medical Conditions

• Advanced liver disease 2
• Active peptic ulcer disease 2
• Diabetic hemorrhagic retinopathy (though visual loss risk must be weighed against stroke benefit) 2

Important Clinical Situations That Are NOT Contraindications

Age

• Patients over 80 years old should receive alteplase within the 3-hour window; this is no longer a contraindication despite being listed in original licensing 3, 4, 5
• Age >80 was the only contraindication independently associated with poor outcome in one large study, but this does not preclude treatment in the 0-3 hour window 5

Mild Stroke

• Mild but potentially disabling symptoms (NIHSS <5) are not a contraindication 4, 5
• Clinical judgment should focus on whether deficits are disabling, not the numerical score 3

Menstruation

• Active menstruation is not a contraindication 1, 2
• Patients may experience increased menstrual flow and rarely require transfusion, especially on the first day of menses 1

Cervical Artery Dissection

• Spontaneous cervical carotid artery dissection is not a contraindication 1, 4
• More than 50 patients have been treated safely without new deficits, subarachnoid hemorrhage, or arterial rupture 1

Cardiac Thrombus

• Known intracardiac thrombus is not an absolute contraindication but requires careful evaluation 1, 2
• Limited data (5 patients) showed no early systemic or cerebral embolism, though late recurrent embolism occurred in one patient 1

Antiplatelet Therapy

• Monotherapy with antiplatelet agents does not preclude alteplase 4
• Combined antiplatelet therapy (aspirin + clopidogrel) allows alteplase, though symptomatic intracerebral hemorrhage risk may be slightly higher 4

Other Conditions

• Seizure at stroke onset is not a contraindication if imaging confirms acute ischemia 4
• 1-10 cerebral microbleeds on prior MRI may be treated 3
• Known sickle cell disease may be treated 3
• End-stage renal disease on hemodialysis with normal aPTT can receive alteplase 4

Critical Pitfalls to Avoid

Time Delays

• Only blood glucose measurement must precede alteplase initiation—do not delay for other laboratory tests 3
• Door-to-needle time should be <60 minutes in 90% of patients 3
• Never wait to assess alteplase response before initiating mechanical thrombectomy evaluation—any delay worsens outcomes 3

Blood Pressure Management

• Treat blood pressure aggressively and rapidly to achieve <185/110 mmHg rather than excluding patients 1, 3
• The contraindication is refractory hypertension, not initial elevation 1

Outdated Contraindications

• Do not exclude patients >80 years in the 0-3 hour window—this is outdated practice 3, 5
• Many original licensing contraindications have been challenged by real-world evidence showing safety in off-label use 5, 6

Thrombocytopenia

• While platelet count <100,000/mm³ is listed as an absolute contraindication 1, 4, at least one case report describes successful treatment despite severe thrombocytopenia in a complex patient with antiphospholipid syndrome 7
• This highlights that in exceptional circumstances, contraindications based on expert opinion rather than clinical evidence may be reconsidered 7

Hemorrhage Risk Factors

The following increase intracranial hemorrhage risk but are not contraindications:

• Advanced age (>65 years, especially >80 years) 2
• Low body weight (<67-70 kg)—requires dose adjustment 2
• Hypertension on admission 2
• Hyperglycemia (>8.4 mmol/L or >180 mg/dL) 2

Evidence Quality Note

A large observational study of 985 patients found that 51% had one or more license contraindications, yet off-label thrombolysis was not associated with poorer clinical outcome (except for age >80 years) or increased symptomatic intracerebral hemorrhage rates 5. This suggests many current contraindications warrant re-evaluation as additional evidence accumulates 5, 6.