What is the frequency of anaphylactic shock after alteplase (tissue plasminogen activator, tPA) infusion?

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Last updated: November 25, 2025View editorial policy

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Frequency of Anaphylactic Shock After Alteplase Infusion

Anaphylactic shock after alteplase infusion is extremely rare, with severe allergic reactions occurring in well under 1% of patients, though the exact incidence is not precisely quantified in major guidelines.

Documented Incidence from Guidelines

The available guideline evidence does not provide specific rates for anaphylactic reactions to alteplase (tissue plasminogen activator). In contrast to streptokinase, which may be associated with hypotension and rare severe allergic reactions, alteplase is structurally identical to endogenous tissue plasminogen activator and therefore should theoretically not induce allergic responses 1.

Evidence from Case Reports and Surveillance Data

While guidelines do not quantify anaphylaxis rates, research evidence provides some insight:

  • A systematic review of the FDA Adverse Event Reporting System (2004-2012) identified only 12 cases of allergic adverse reactions directly attributable to IV thrombolytics (11 with alteplase, 1 with reteplase) out of 924 total adverse events reviewed 2.

  • Allergic reactions documented included angioedema, facial swelling, urticaria, skin rash, hypotension, anaphylactic shock, and one death (the fatal case involved reteplase, not alteplase) 2.

  • Individual case reports have documented IgE-mediated anaphylactic reactions to alteplase, including one case with confirmed IgE antibodies reactive to alteplase, suggesting true anaphylaxis can occur even without prior exposure 3.

Clinical Context and Risk Factors

The most important risk factor for angioedema (not true anaphylaxis) after alteplase is concomitant use of angiotensin-converting enzyme (ACE) inhibitors, which significantly increases the risk of orolingual angioedema 4. This represents a different mechanism than IgE-mediated anaphylaxis.

Orolingual angioedema occurs in approximately 1-5% of stroke patients receiving alteplase, particularly those on ACE inhibitors, but this is distinct from systemic anaphylactic shock 5, 6, 4.

Management Implications

  • Most allergic reactions to alteplase resolve with withdrawal of the medication and treatment with diphenhydramine and steroids ± epinephrine 2.

  • The American Heart Association recommends that if severe reactions occur during alteplase infusion, the infusion should be stopped immediately and emergency management initiated 1.

  • Patients on ACE inhibitors should be monitored closely for angioedema during and after alteplase administration, though this should not delay treatment in eligible stroke patients 5, 4.

Key Clinical Pitfall

Do not confuse orolingual angioedema (relatively more common at 1-5%, especially with ACE inhibitor use) with true anaphylactic shock (extremely rare, <0.1%) 2, 6, 4. The former is a localized reaction requiring airway management, while the latter is a systemic life-threatening emergency requiring full anaphylaxis protocols.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Anaphylactic shock associated with intravenous thrombolytics.

The American journal of emergency medicine, 2014

Guideline

Alteplase Administration for Acute Ischemic Stroke

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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