What is the bleeding risk in patients with acute ischemic stroke treated with tenecteplase (tissue plasminogen activator)?

Bleeding Risk with Tenecteplase in Acute Ischemic Stroke

Tenecteplase carries a symptomatic intracranial hemorrhage (ICH) risk of approximately 3-6% in acute ischemic stroke patients, which is comparable to alteplase and does not represent an increased bleeding risk compared to the standard thrombolytic agent. 1, 2

Overall Hemorrhage Rates

The bleeding risk profile of tenecteplase is well-established through recent high-quality evidence:

• Symptomatic ICH occurs in 3.0-3.1% of patients treated with tenecteplase, compared to 2.5% with alteplase, showing no statistically significant difference (RR = 1.21,95% CI 0.92-1.59) 1
• Any intracranial hemorrhage occurs in approximately 13.2% of tenecteplase-treated patients versus 12.7% with alteplase (RR = 1.02,95% CI 0.8-1.24), demonstrating equivalent overall bleeding risk 1
• Asymptomatic ICH occurs in 8.7% of tenecteplase patients compared to 9.0% with alteplase, with no significant difference 1

The ORIGINAL trial, the most recent and highest quality study comparing tenecteplase to alteplase in 1,465 patients, found identical symptomatic ICH rates of 1.2% in both groups, with 90-day mortality of 4.6% versus 5.8% respectively 2

Dose-Dependent Bleeding Risk

The bleeding risk varies significantly based on tenecteplase dosing:

• At 0.25 mg/kg (the recommended dose), symptomatic ICH rates remain low at 1.2-3.0% 2, 3
• At 0.5 mg/kg, symptomatic ICH increases substantially to 15%, making this dose unsafe 4
• Doses of 0.1-0.4 mg/kg have been established as safe, with no symptomatic ICH at 0.1 mg/kg and acceptable rates at 0.2-0.4 mg/kg 4

The American Heart Association recommends tenecteplase as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion (Class IIb, Level B-R) 5

Types and Locations of Hemorrhage

Hemorrhage patterns are similar between tenecteplase and alteplase:

• Intraventricular hemorrhage, subarachnoid hemorrhage, hemorrhagic infarction, parenchymal hematoma, and remote parenchymal hematoma all occur at comparable rates between the two agents 1
• Parenchymal hematoma (PH) specifically occurs in 9.5% of tenecteplase-treated patients and is significantly associated with poorer functional outcomes and death at 3 months 6

Independent Predictors of Hemorrhage

Specific patient factors increase bleeding risk with tenecteplase:

• Older age increases risk (aOR = 1.03 per year) 6
• Male gender doubles the risk (aOR = 2.07) 6
• History of hypertension doubles the risk (aOR = 2.08) 6
• Higher baseline NIHSS score increases risk (aOR = 1.07 per point) 6
• Higher admission blood glucose increases risk (aOR = 1.12 per unit increase) 6

Extended Time Window Considerations

When tenecteplase is used in the 4.5-24 hour window (in selected patients with salvageable tissue on perfusion imaging):

• Symptomatic ICH occurs in 3.0% of patients, compared to 0.8% with standard medical treatment 3
• This represents an absolute increase of 2.2% in symptomatic ICH risk, yielding a number needed to harm of approximately 45 patients 3
• Despite this increased bleeding risk, treatment still results in better functional outcomes (33.0% with mRS 0-1 versus 24.2% with standard treatment) 3

Critical Safety Context

The bleeding risk must be weighed against treatment benefits:

• Treatment with alteplase (and by extension tenecteplase) is associated with an absolute 6% increase in symptomatic ICH (7% with thrombolysis versus 1% without), yielding a number needed to harm of 17 7
• However, the number needed to treat for favorable outcomes is 8-14, meaning the benefit substantially outweighs the bleeding risk in appropriately selected patients 7
• Mortality at 90 days is similar or lower with tenecteplase (4.6-13.3%) compared to alteplase or standard treatment 2, 3

Common Pitfalls to Avoid

• Do not confuse stroke dosing (0.25 mg/kg, max 25 mg) with myocardial infarction dosing (0.5 mg/kg), as the higher dose dramatically increases ICH risk to 15% 5, 4
• Do not withhold tenecteplase due to fear of bleeding in appropriately selected patients, as the absolute benefit exceeds the bleeding risk 7
• Do not administer tenecteplase to patients on direct oral anticoagulants without specialized testing and reversal agents available, as this substantially increases bleeding risk 7
• Ensure blood pressure is controlled to <185/110 mmHg before administration to minimize hemorrhage risk 7