Laboratory Testing in Anaphylaxis

Essential Tryptase Sampling Protocol

The American College of Allergy, Asthma, and Immunology recommends a three-sample tryptase protocol for accurate diagnosis of anaphylaxis, with samples drawn immediately during resuscitation, at 1-2 hours post-symptom onset, and at 24 hours or during convalescence 1, 2, 3
The first sample should be drawn as soon as feasible after resuscitation has started, with 5-10 mL of clotted blood, and should not delay resuscitation 1, 4
The second sample should be obtained at 1-2 hours after the start of symptoms 1, 2, 3
The third sample should be collected at 24 hours or during convalescence to establish baseline tryptase levels, as some individuals have naturally elevated baseline levels 1, 5
All samples should be labeled with the exact time and date of collection 1, 3

Approximately 5-7% of the population has elevated baseline tryptase levels unrelated to anaphylaxis, which would lead to false-positive interpretation if only acute samples are drawn 6

Allergen-specific IgE testing can be drawn during the acute reaction or shortly afterward, but should be repeated 4-6 weeks later if initially negative, as IgE antibodies may be temporarily consumed during the acute reaction 6

Approximately 23.6% of allergic reactions are non-IgE-mediated and will have negative blood tests despite true clinical allergy 6
Never rule out anaphylaxis based on negative IgE testing alone 6
The presence of drug-specific IgE indicates sensitization but is not proof that the drug caused the reaction 6
Sensitization does not equal clinical allergy—many patients with positive IgE tests tolerate the allergen without symptoms 6

Arterial blood gas determination should guide oxygen therapy where hypoxemia is a concern 7
Continuous pulse oximetry is essential for monitoring respiratory status 7
Hemodynamic monitoring is essential when administering intravenous epinephrine 7

Do not delay treatment to obtain laboratory confirmation, as the diagnosis of anaphylaxis is clinical, and epinephrine administration should never be postponed while waiting for tryptase results 1, 4