Anaphylaxis TNK/TPA

-Alteplase(TPA) or TNK-  Anaphylaxis
--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

-Clinical Presentation
--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

-Mechanisms -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

-Diagnosis and Monitoring
--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

-Management
--ASK FOR HELP; Don't be shy to call a CODE BLUE; STAT-ED  or ICU Staff Consult
--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 IM)
--May require intubation and ICU transfer
--Risk-benefit analysis before re-challenge after Type 1 reaction
--Consider to speak 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

-Outcomes
--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