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What is the indication and cobtraindication of thrombolysis in acute ischemic stroke

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"ischemic stroke" AND "thrombolysis" AND "indications contraindications"

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"acute ischemic stroke" AND "alteplase" AND "guidelines"

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I have all the information needed from Harrison's. The table data from line 2511 was truncated - let me check what the full table contained by looking at the raw content more carefully. The snippet I got from the FTS search showed the table content. Let me now compile the full answer.
Based on Harrison's Principles of Internal Medicine 22E (2025), here is the complete clinical answer:

Thrombolysis in Acute Ischemic Stroke

The standard agent is IV recombinant tissue plasminogen activator (rtPA / alteplase), dosed at 0.9 mg/kg (max 90 mg) - 10% as a bolus, the remainder over 60 minutes. Tenecteplase (0.25 mg/kg IV bolus, max 25 mg) is increasingly used as an alternative because it does not require a 1-hour infusion.

INDICATIONS

CriterionDetail
Clinical diagnosis of strokeAcute neurological deficit consistent with focal ischemia
Symptom onset to drug administration≤ 3 hours (approved in the US); ≤ 4.5 hours in Europe and Canada (with additional restrictions)
CT scanNo hemorrhage, no edema > 1/3 of the MCA territory
Age≥ 18 years
Key evidence: The NINDS rtPA Stroke Study demonstrated a 12% absolute increase in patients with minimal disability (32% placebo vs. 44% rtPA) despite a higher rate of symptomatic intracranial hemorrhage (6.4% vs. 0.6%). ECASS III confirmed benefit in the 3-4.5 hour window (52.4% good outcome vs. 45.2% on placebo).
Extended window (beyond 4.5 h): Advanced neuroimaging (MRI perfusion-diffusion mismatch, CT perfusion) can identify patients who may still benefit. Two trials using MRI selection beyond 4.5 h have shown clinical benefit.

CONTRAINDICATIONS

ContraindicationNotes
Sustained BP > 185/110 mmHg despite treatmentMust lower BP before giving rtPA
Bleeding diathesisIncludes coagulopathy, thrombocytopenia
Recent head injury or prior intracerebral hemorrhageAbsolute contraindication
Major surgery in preceding 14 daysRisk of wound bleeding
Gastrointestinal bleeding in preceding 21 daysActive or recent GI bleed
Recent myocardial infarctionIncreases risk of myocardial rupture or pericarditis hemorrhage
Additional restrictions for the 3-4.5 h window (ECASS III criteria):
  • Age > 80 years (excluded in original ECASS III)
  • Diabetic patients with a prior stroke history
Anticoagulant use before stroke: Patients on anticoagulants at therapeutic levels are generally excluded from IV thrombolysis due to bleeding risk (specifically addressed in Rosen's Emergency Medicine as a separate consideration).

Blood Pressure Management Before Thrombolysis

BP must be reduced to < 185/110 mmHg before rtPA is administered. If BP cannot be controlled to this threshold, thrombolysis should not be given.

Tenecteplase vs. Alteplase (Recent Evidence)

Two recent meta-analyses (PMID 38782799 and 39413337, both 2024) confirm tenecteplase is non-inferior to alteplase with a similar safety profile. Tenecteplase is preferred when patients require rapid transfer for mechanical thrombectomy, as the single-bolus dosing eliminates the need for a 1-hour infusion during transport.

When Thrombolysis Is Not Sufficient Alone

For large-vessel occlusions (MCA, intracranial ICA, basilar artery), IV thrombolysis frequently fails to recanalize the vessel due to large clot burden. Mechanical thrombectomy is indicated in these cases, either instead of or in addition to IV thrombolysis, up to 6 hours (and beyond in selected patients with salvageable penumbra on imaging).
Source: Harrison's Principles of Internal Medicine 22E (2025), Table 438-1 - "Administration of Intravenous Recombinant Tissue Plasminogen Activator (rtPA) or Tenecteplase for Acute Ischemic Stroke"
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