Evaluation of autopsy cases in which anaphylaxis in the context of allergen exposure or mast cell activation is a suspected cause of death
Fluorescence Enzyme Immunoassay (FEIA)
Mast Cell Tryptase
Serum
Collection Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Submission Container/Tube: Plastic vial
Specimen Volume: 0.5 mL
Collection Instructions: Centrifuge and aliquot serum into plastic vial.
Additional Information: Tryptase degenerates very quickly when left in the presence of red blood cells.
0.2 mL
Gross hemolysis | OK |
Gross lipemia | OK |
Gross icterus | OK |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Serum | Frozen (preferred) | 14 days | |
Refrigerated | 7 days |
Evaluation of autopsy cases in which anaphylaxis in the context of allergen exposure or mast cell activation is a suspected cause of death
Tryptase, a neutral protease, is a dominant protein component of the secretory granules of human mast cells. There are 2 forms of tryptase, designated as alpha and beta, which are encoded by 2 separate genes.(1) Both are expressed as inactive proenzymes. Alpha-protryptase and beta-protryptase are spontaneously released from resting mast cells. The levels of the protrypases reflect the total number of mass cells within the body but are not an indication of mast cell activation. Beta-protryptase is processed to a mature form, which is stored in granules and released as an active tetramer that is bound to heparan or chondroitin sulfate proteoglycans. In contrast, an amino acid change in alpha-protryptase prevents processing to a mature form. Upon mast cell activation, degranulation releases mature tryptase, which is almost exclusively in the form of beta-tryptase.
During an anaphylactic episode, mast cell granules release tryptase; measurable amounts are found in blood, generally within 30 to 60 minutes.(2) The levels decline under first-order kinetics with a half-life of approximately 2 hours. Severe anaphylactic reactions can lead to fatal airway, respiratory, and circulatory compromise. Anaphylaxis as a cause of death may be suspected in individuals with a known history of allergy, previous anaphylactic episodes, or based on autopsy evidence including mucous plugging, hyperinflated lungs, and petechial hemorrhages.(3) Measurement of tryptase in postmortem serum samples may be useful in investigating deaths in which anaphylaxis is suspected. However, interpretation of results can be difficult, as the reference value for routine diagnostic testing is not applicable to postmortem samples. A recent study identified a concentration of 53.8 mcg/L for postmortem tryptase, which resulted in a sensitivity of 89% and a specificity of 93% for the identification of anaphylaxis as the cause of death.(4) However, it is unclear how widely applicable this cutoff value is, given the complexities of postmortem specimen collection and biological processes.
No established reference values
Increased concentrations of total tryptase may indicate mast cell activation occurring as a result of anaphylaxis or allergen challenge, or it may indicate an increased number of mast cells as seen in patients with mastocytosis. However, no specific cutoff value has been widely validated for autopsy specimens.
Tryptase may be low or undetectable in individuals with acute mast cell activation if specimens are obtained greater than 12 hours after an anaphylactic episode.
It is recommended that postmortem tryptase be measured in serum obtained from peripheral blood sources, such as the femoral vessels.
Postmortem tryptase concentrations may be affected by specimen collection technique and length of postmortem interval prior to specimen collection
1. Lyons JJ, Yi T: Mast cell tryptases in allergic inflammation and immediate hypersensitivity. Curr Opin Immunol. 2021;72:94-106. doi: 10.10.16/j.coi.2021.04.001
2. Platzgummer S, Bizzaro N, Bilo MB, et al: Recommendations for the use of tryptase in the diagnosis of anaphylaxis and clonal mast cell disorders. Eur Ann Allergy Clin Immunol. 2020 Mar;52(2):51-61. doi:10.23822/EurAnnACI.1764-1489.133
3. Garland J, Ondruschka B, Broi UD, et al: Post mortem tryptase: a review of literature on its use, sampling and interpretation in the investigation of fatal anaphylaxis. Forensic Sci Int. 2020 Sep;314:110415. doi: 10.1016/j.forsciint.2020.110415
4. Tse R, Wong CX, Kesha K, et al: Post mortem tryptase cut-off level for anaphylactic death. Foresnic Sci Int. 2018 Mar;284:5-8. doi: 10.1016/j.forsciint.2017.12.035
Antitryptase, covalently coupled to ImmunoCAP, reacts with tryptase in the patient serum specimen. After washing, enzyme-labeled antibodies against tryptase are added to form a complex. After incubation, unbound enzyme-labeled antibodies are washed away, and the bound complex is incubated with a developing agent. After stopping the reaction, the fluorescence in the eluate is measured. The fluorescence is directly proportional to the concentration of tryptase in the serum specimen.(Package insert: ImmunoCAP Tryptase. Phadia AB; 10/2019)
Monday through Friday
This test has been modified from the manufacturer's instructions. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
83520
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
TRYPA | Tryptase, Autopsy | 21582-2 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
TRYPA | Tryptase, Autopsy | 21582-2 |