What are the contraindications for tissue plasminogen activator (tPA) administration after a stroke?

Contraindications for tPA Administration After Acute Ischemic Stroke

tPA is absolutely contraindicated in patients with intracranial hemorrhage, prior intracranial hemorrhage, recent stroke or head trauma within 3 months, uncontrolled hypertension (SBP >185 or DBP >110 mmHg), active bleeding, or coagulopathy (INR >1.7, platelets <100,000/mm³). 1

Absolute Contraindications (Within 3-Hour Window)

Historical Factors

• Significant head trauma or prior stroke within the previous 3 months 1
• History of any prior intracranial hemorrhage 1
• Intracranial neoplasm, arteriovenous malformation, or aneurysm 1
• Recent intracranial or intraspinal surgery 1
• Symptoms suggesting subarachnoid hemorrhage 1

Bleeding Risk Factors

• Active internal bleeding 1
• Arterial puncture at a noncompressible site within the previous 7 days 1
• Acute bleeding diathesis, including:
  • Platelet count <100,000/mm³ 1
  • Heparin use within 48 hours with elevated aPTT above upper limit of normal 1
  • Current anticoagulant use with INR >1.7 or PT >15 seconds 1
  • Current use of direct thrombin inhibitors or direct factor Xa inhibitors with elevated laboratory tests 1

Physiological Parameters

• Elevated blood pressure: systolic >185 mmHg or diastolic >110 mmHg 1, 2
• Blood glucose concentration <50 mg/dL (2.7 mmol/L) 1

Imaging Findings

• CT demonstrates multilobar infarction (hypodensity >1/3 cerebral hemisphere) 1
• Any evidence of intracranial hemorrhage on CT or MRI 1

Additional Exclusion Criteria for 3-4.5 Hour Window

Beyond the standard 3-hour contraindications, patients treated between 3-4.5 hours have additional exclusions: 1

• Age >80 years 1
• Severe stroke with NIHSS >25 1
• Taking any oral anticoagulant regardless of INR 1
• History of both diabetes mellitus AND prior ischemic stroke 1

Relative Contraindications (Require Risk-Benefit Assessment)

These conditions warrant careful consideration but are not absolute contraindications: 1

• Only minor or rapidly improving stroke symptoms (clearing spontaneously) 1
• Pregnancy 1
• Seizure at onset with postictal residual neurological impairments 1
• Major surgery or serious trauma within previous 14 days 1
• Recent gastrointestinal or urinary tract hemorrhage within previous 21 days 1
• Recent acute myocardial infarction within previous 3 months 1

Important Clinical Nuances

Antiplatelet Therapy

Prestroke antiplatelet use is NOT an absolute contraindication. Patients on aspirin alone have a slightly increased risk of symptomatic intracranial hemorrhage (sICH rate 5.0% vs 3.7%), but demonstrate better functional outcomes and independent ambulation at discharge compared to those not on antiplatelet therapy. 3 Dual antiplatelet therapy (aspirin plus clopidogrel) carries higher bleeding risk (sICH AOR 1.47) but remains a relative rather than absolute contraindication. 3

Microhemorrhages on MRI

**Small numbers of microhemorrhages (<5) detected on gradient-echo MRI sequences do not contraindicate tPA administration.** 1 However, the risk in patients with multiple microbleeds (>5) remains uncertain and requires individualized assessment. 1

Laboratory Testing Timing

Treatment can be initiated before coagulation results are available in patients without recent anticoagulant or heparin use, but must be discontinued if INR >1.7 or platelet count <100,000/mm³ when results return. 1

Early Ischemic Changes on CT

Minor ischemic changes on baseline CT are NOT contraindications to treatment. Only frank hypodensity involving >1/3 of the MCA territory constitutes a contraindication. 1 Early infarct signs were present in 31% of NINDS trial patients, and tPA benefits were similar regardless of their presence. 1

Common Pitfalls to Avoid

Unnecessarily excluding patients based on outdated criteria. Many original NINDS exclusion criteria have proven overly restrictive in real-world practice, and relaxed criteria could increase treatment rates to 20% without compromising safety. 4

Failing to aggressively manage blood pressure before treatment. Blood pressure must be reduced to <185/110 mmHg before tPA administration and maintained ≤180/105 mmHg for 24 hours post-treatment. 2 This is achievable in most patients and should not automatically exclude them from treatment.

Overlooking the time-dependent nature of contraindications. The 3-4.5 hour window has stricter exclusion criteria than the 0-3 hour window, particularly regarding age, stroke severity, anticoagulation, and diabetes with prior stroke. 1

Misinterpreting protocol violations as treatment failures. In the STARS study, 32.6% of patients had protocol violations (including treatment beyond 3 hours in 13.4%), yet overall outcomes remained favorable with 35% achieving excellent outcomes and only 3.3% experiencing symptomatic ICH. 5