Anaphylaxis to TNK/TPA

Incidence unknown but likely underestimated

Early data: 4 cases in >1 million doses (very low)

Recent studies suggest higher: up to 1.9% in stroke patients

Medicare study: 8-fold increased risk with IV thrombolysis (OR 7.8)

Absolute risk still small: 0.54% vs 0.07% without thrombolysis

Risk context: anaphylaxis 1 in 200 vs ICH 1 in 16 vs orolingual angioedema 1 in 45

Can occur after bolus and/or during infusion

Spectrum from orolingual angioedema (2.2% incidence) to full anaphylaxis

Classic signs: urticaria, angioedema, bronchospasm, hypotension

Additional: erythema, laryngeal edema, arrhythmias, feeling of doom

Rapid onset suggests more severe reaction

Largely clinical diagnosis

Type 1 hypersensitivity (IgE-mediated) rare given low antigenicity

More likely systemic hypersensitivity from vasoactive mediator release

Mast cell/basophil release: histamine, tryptase, leukotrienes

ACE inhibitor interaction increases orolingual angioedema risk

Plasmin activates complement → kinins; ACE-I blocks bradykinin breakdown

Anaphylaxis can be prothrombotic and reduce cerebral blood flow

Clinical diagnosis primary

Serum tryptase: rise >2 μg/L has moderate sensitivity, high specificity

• Best compared to baseline; correlates with severity

• Useful postmortem if obtained <15 hours

• Specific IgE to alteplase detectable but research-only

Guidelines emphasize frequent cardiopulmonary monitoring post-thrombolysis

Watch for facial angioedema and respiratory distress during infusion

ASK FOR HELP. Don't be shy to call a CODE BLUE.

Minor reaction: Stop infusion immediately to prevent dose-dependent escalation.

Severe reaction protocol:

• IV hydrocortisone (200mg IVP)

• IV ranitidine (25-50mg IVP)

• IM Epinepherine (0.3-0.5mg)

May require intubation and ICU transfer

Risk-benefit analysis before re-challenge after Type 1 reaction

Consider speaking with Bloodbank/Transfusion specialist on call:

• Consider Berinert (C1 esterase inhibitor) for refractory cases

  • Plasma-derived C1 esterase inhibitor can be effective when standard treatment fails

  • Particularly useful given bradykinin-mediated mechanism

• Case reports show resolution of airway compromise and avoidance of invasive airway procedures

Risk-benefit analysis before re-challenge after Type 1 reaction

Medicare study: anaphylaxis associated with higher mortality (OR 1.9)

Case reports describe stroke following anaphylaxis via prothrombotic mechanisms

Reduced cerebral blood flow from decreased cardiac output and vasospasm