Postmortem tryptase as a diagnostic marker in fatal anaphylaxis: A systematic review and meta-analysis

Fatal anaphylaxis remains a diagnostically challenging condition in forensic practice, particularly in the postmortem setting where clinical information is often limited. Postmortem serum tryptase has been widely proposed as a marker of mast cell activation, but its quantitative significance and diagnostic performance have not been consistently defined. This systematic review and meta-analysis aimed to evaluate both the magnitude of tryptase elevation and its diagnostic accuracy in fatal anaphylaxis. Seven studies were included, comprising 105 anaphylactic deaths and 449 non-anaphylactic controls. Continuous meta-analysis demonstrated a marked increase in postmortem tryptase concentrations in anaphylactic deaths, with a pooled ratio of means of 8.68 (95% confidence interval 2.12-35.57). Diagnostic meta-analysis showed good overall performance, with pooled sensitivity of 0.80 and specificity of 0.92, and an area under the receiver operating characteristic curve of 0.94. These findings were consistent across sensitivity analyses despite substantial heterogeneity in study design and methodology. Although reported diagnostic cut-off values varied widely, most studies using standardized methods and femoral blood sampling showed clustering of thresholds within a relatively narrow range. However, this pattern should be interpreted as descriptive rather than indicative of a universal threshold. Postmortem tryptase is strongly associated with fatal anaphylaxis and represents a valuable additional marker in forensic investigations. Its interpretation, however, must be integrated with clinical, circumstantial, and autopsy findings. The lack of methodological standardization remains a major limitation, and future studies adopting harmonized protocols are needed to improve diagnostic reliability.