Postmortem tryptase cutoff points and main causes of fatal anaphylaxis

Medicolegal Implications of Biphasic Anaphylaxis

“…[20][21][22][23][76][77][78][79] The current analytes in use, which are tryptase, total and specific IgE, and histamine, because of their limitations, are considered not fully reliable in clinical and postmortem diagnosis of anaphylaxis and must always carefully interpreted and contextualized. 13,79,80,[88][89][90][91][92][93][94][95][96][97][98][99] Further research into the kinetics of other anaphylaxis biomarkers (such as chymase and carboxypeptidase A3), with stable high blood levels (both premortem and postmortem) and a half-life longer than tryptase, is needed. This may produce new emergency laboratory procedures and protocols for monitoring the onset of a biphasic reaction.…”

“…(2) the analysis of histamine levels is not reliable at postmortem because its rapid metabolism; (3) total and specific IgE levels, although stable for weeks postmortem, may be absent in people suffering from anaphylaxis; (4) tryptase (upper limit for living subjects 11.4 μg/L) whose levels are generally stable for some days after death (postmortem cutoff of 23 μg/L was recently determined by Garland et al in cases of nonanaphylactic death) may be within normal limits even in cases of fatal anaphylactic shock; (5) tryptase levels are affected by numerous factors (such as postmortem interval, hemolysis, resuscitation procedures, trauma, acute cardiovascular disease, bacterial/viral infections, drug overdose, sudden infant death syndrome, mastocytosis). 13,79,80,[88][89][90][91][92][93][94][95][96][97][98][99] Therefore, the levels of the analytes currently in use, such as tryptase and total/specific IgE, should always be carefully interpreted in the context of the wider clinical history, symptoms, and postmortem findings. 13,79,80,[88][89][90][91][92][93][94][95][96][97][98][99] Studies of biphasic anaphylaxis make it clear that the second reaction, especially cases where death results, often appears around an hour after the primary reaction.…”

“…13,79,80,[88][89][90][91][92][93][94][95][96][97][98][99] Therefore, the levels of the analytes currently in use, such as tryptase and total/specific IgE, should always be carefully interpreted in the context of the wider clinical history, symptoms, and postmortem findings. 13,79,80,[88][89][90][91][92][93][94][95][96][97][98][99] Studies of biphasic anaphylaxis make it clear that the second reaction, especially cases where death results, often appears around an hour after the primary reaction. [2][3][4][6][7][8]19,[23][24][25][26][27]30,32,33,39,[63][64][65]…”

“…- Identification of markers of anaphylactic death —The use of analytes, such as tryptase, total and specific IgE and hystamine have several limitations in both clinical and postmortem diagnoses: (1) during emergency situations, for both uniphasic or biphasic anaphylaxis, the common laboratory procedures used to detect and quantify these analytes take a relatively long time and are not routinely performed in acute premortem phases because they are of no help in diagnosis and/or ongoing treatment; (2) the analysis of histamine levels is not reliable at postmortem because its rapid metabolism; (3) total and specific IgE levels, although stable for weeks postmortem, may be absent in people suffering from anaphylaxis; (4) tryptase (upper limit for living subjects 11.4 μg/L) whose levels are generally stable for some days after death (postmortem cutoff of 23 μg/L was recently determined by Garland et al in cases of nonanaphylactic death) may be within normal limits even in cases of fatal anaphylactic shock; (5) tryptase levels are affected by numerous factors (such as postmortem interval, hemolysis, resuscitation procedures, trauma, acute cardiovascular disease, bacterial/viral infections, drug overdose, sudden infant death syndrome, mastocytosis) 13,79,80,88–99 …”

Fatal food-induced anaphylaxis: Determination of tryptase and specific IgE on cadaveric blood samples. What else for a better methodological standard?

“…22 Moreover, Tejedor-Alonso point out that the best cutoff point for postmortem tryptase in anaphylaxis is 40-60 mg/l, differentiating anaphylaxis due to drugs and Hymenoptera, comparing to anaphylaxis due to food (tryptase values were more than double of those deaths due to foods). 23 Similarly, Platzgummer states that in food anaphylaxis, tryptase levels are usually lower than those observed in drug-induced anaphylaxis. 24 Certainly, the argument about the validity of the current laboratory markers used for the post-mortem diagnosis of anaphylaxis is constantly evolving.…”