Mast cell tryptase in postmortem serum—reference values and confounders

Abstract

We have investigated the effects of some factors suspected of inducing spuriously increased tryptase concentrations, specifically sampling site, conjunctival petechial bleeding and prone position at the time of death as indicators of premortem asphyxia, and resuscitation efforts by external cardiac massage. Tryptase was measured in blood from the femoral vein in 60 deaths: 39 control cases who died rapidly (within minutes) from natural causes (sudden cardiac death and acute aortic dissection), 16 with death caused by prolonged asphyxia (traumatic compression of the chest and suffocation due to body position or smothering), and five anaphylactic deaths. In 44 of these cases, tryptase was measured in both heart and femoral blood. Mast cell tryptase was analyzed with a commercial FEIA method (Pharmacia Diagnostics AB, Uppsala, Sweden) measuring both alpha- and beta-tryptase. Assuming that tryptase values in the control group were gamma distributed, we calculated the upper normal limits for tryptase concentrations in femoral blood. It was found that 95% of the controls had values below 44.3 mug/l (femoral blood), SD 5.27 mug/l. All but one of the anaphylactic deaths had tryptase concentrations exceeding that limit. Tryptase was significantly elevated in femoral blood from anaphylactic deaths (p<0.007), compared with the controls. Also, in the cases where death had occurred due to asphyxia tryptase was elevated in femoral blood (p<0.04). A significant difference in tryptase concentrations was seen between blood from the heart and the femoral vessels (p<0.02) in the whole material (n=44). Tryptase concentrations in femoral blood were not influenced by prone position at death, or resuscitation efforts. It is concluded that asphyxia premortem seems to affect tryptase concentrations, that postmortem tryptase measurements should be done in serum from femoral blood, and that the normal upper limit, covering 95%, is 44.3 microg/l.

Deaths from bee stings: a report of three cases from Pretoria, South Africa

“…[24] A reasoned conclusion as to the probable cause of death can only be arrived at if there is due regard for all relevant perspectives, including clinical / medical history, information pertaining to the terminal event(s), anatomical (autopsy / histology) findings, as well as biochemical / humoral findings. [5][6][7][21][22][23][24] We support the proposals by Riches et al in the classification of these deaths, in an attempt to achieve greater clarity and insight into these often tragic deaths. [5] Key points:…”

“…[20] The exact level of tryptase which should support the diagnosis of anaphylaxis also differs in the literature and is said to be influenced by post mortem interval, site of collection and cause of death. [7,18,21,22]. Edston et al reported in 2007 that typtase levels should be taken from femoral blood and that the normal upper level in 95% of cases was recorded as 44.3μg/l.…”

“…Edston et al reported in 2007 that typtase levels should be taken from femoral blood and that the normal upper level in 95% of cases was recorded as 44.3μg/l. [21] In 2015 McLean-Took et al stated that aortic samples should be taken and that values of >110μg/l can support the diagnosis of anaphylaxis, but the authors emphasise that the diagnosis should not be made solely on the value of the tryptase levels. [22] The interpretation of IgE levels should also be done with caution in the post mortem setting.…”

Postmortem chemistry update part II

“…Tryptase is more stable, has a longer half-life and can be detected from a few minutes up to several hours after mast cell degranulation [99,100]. Analyses of tryptase in postmortem serum samples of suspected anaphylaxis and anaphylactoid reactions have consistently shown elevated values [99][100][101][102][103][104][105][106][107][108][109][110][111][112]. However, increased tryptase levels have also been demonstrated in other situations, including sudden death infant syndrome, acute death after heroin injection, atherosclerotic cardiovascular disease, and traumatic death [100,111,[113][114][115][116][117][118][119][120][121][122].…”

“…A weak positive correlation between heart blood and pericardial fluid also suggested the possibility of postmortem diffusion between these compartments. In a study performed in 2007 on 60 cases, including five anaphylactic deaths, Edston et al [111] measured tryptase in postmortem serum from femoral and heart blood and proposed a value of 45 μg/l in postmortem serum from femoral vein blood as a reference limit in order to eliminate the possibility of false positives.…”