What tryptase level indicates anaphylaxis?

Tryptase Levels in Anaphylaxis

The change in tryptase concentration is more valuable than absolute values for diagnosing anaphylaxis, with a rise of at least 20% + 2 μg/L from baseline being diagnostic, while an absolute level >11.4 μg/L during a reaction suggests anaphylaxis, especially in severe cases. 1, 2

Understanding Tryptase in Anaphylaxis

What is Tryptase?

• Tryptase is an enzyme primarily released by mast cells during degranulation, with two main forms: α-tryptase (constitutively secreted) and β-tryptase (released during anaphylaxis) 1
• Normal serum tryptase range is 0-11.4 μg/L 2
• β-tryptase is the form specifically released during anaphylactic reactions 1

Tryptase Kinetics During Anaphylaxis

• Serum tryptase levels peak approximately 1-1.5 hours after onset of anaphylaxis 1
• Levels can persist for up to 5 hours after symptom onset 1
• The optimal time to measure serum tryptase is between 1-2 hours but no longer than 6 hours after symptom onset 1
• Tryptase has a half-life of approximately 2 hours in circulation, causing levels to fall rapidly following an anaphylactic reaction 1

Diagnostic Thresholds for Anaphylaxis

Absolute Tryptase Levels

• An absolute tryptase level >11.4 μg/L during a reaction suggests anaphylaxis 3
• Sensitivity of this threshold alone is approximately 72% with specificity of 72% 3
• Elevated levels are more common in severe anaphylaxis (odds ratio 6.5) 4
• In hypotensive anaphylaxis, sensitivity increases to 85% and specificity to 92% 3

Change in Tryptase Levels (Delta Tryptase)

• The change in tryptase concentration is more helpful than absolute values 1
• A rise of at least 20% + 2 μg/L from the individual's baseline is diagnostic for mast cell activation 2
• Alternative calculation: reaction level ≥ 2 ng/mL + 1.2 × baseline tryptase level 4
• Using delta tryptase improves diagnostic sensitivity, particularly when baseline levels are measured within 2 months of the reaction 4

Important Clinical Considerations

Factors Affecting Tryptase Levels

• Intravenous fluid administration during treatment dilutes blood and can lower measured tryptase concentration 1
• Not all anaphylaxis cases show elevated tryptase (up to 36.3% of cases may have normal levels) 5
• Anaphylaxis triggered by drugs tends to show higher tryptase elevations than food-induced anaphylaxis 5
• Severe reactions are more likely to show elevated tryptase levels 4

Limitations and Pitfalls

• Anaphylaxis can occur through basophil or complement activation pathways that don't cause tryptase elevation 1
• A normal tryptase level does not rule out anaphylaxis 1
• The current tryptase assay has high specificity but relatively low sensitivity 1
• Elevated baseline tryptase may indicate systemic mastocytosis (typically >20 μg/L) or hereditary alpha-tryptasemia 6

Optimal Testing Protocol

• Measure acute tryptase 30 minutes to 2 hours after symptom onset 6
• Obtain baseline tryptase at least 24 hours after resolution of symptoms 6
• Compare reaction level to baseline using either the 20% + 2 μg/L rule or an acute/baseline ratio of 1.685 6
• For postmortem diagnosis, tryptase levels may be helpful but have lower predictive value than samples taken during life 1