An outbreak of severe coagulopathy in northern Israel among users of illicit synthetic cannabinoids adulterated with brodifacoum.

INTRODUCTION: Adulteration of illicit drugs is a well-known phenomenon that may expose consumers to unexpected adverse effects. We report a large outbreak of severe coagulopathy in northern Israel during nine months in 2021-2022 among users of synthetic cannabinoids adulterated with a long-acting anticoagulant, brodifacoum. METHODS: We performed a retrospective cohort study based on data extracted from the Israeli National Poison Information Center database and from electronic medical patient records at three participating hospitals. Confiscated drug samples and blood samples obtained at admission in a subgroup of patients were tested for the presence of long-acting anticoagulants. RESULTS: We identified 98 patients affected by the outbreak. All patients had a prolonged international normalized ratio on admission, and in 69%, the blood was non-coagulating. For patients treated in the three participating centers (n = 72), the presenting complaint was overt bleeding in 79% of patients, most commonly in the urinary (53%) and gastrointestinal tracts (50%). The most severe complications were intracranial bleeding (4%), hemothorax (3%), pericardial bleeding (1%), and four patients died. Brodifacoum was detected in all available blood samples (median concentration 207 µg/L, interquartile range 112-349 µg/L, range 45-1,118 µg/L), and the drug samples contained both brodifacoum and the synthetic cannabinoid ADB-BUTINACA. All patients were treated with high-dose phytomenadione (vitamin K1) and additionally by packed red blood cell transfusions, fresh frozen plasma, and/or 4-factor prothrombin complex concentrate when indicated. The most frequent phytomenadione (vitamin K1) dose regimen was initially 20 mg intravenously every eight hours, and at discharge, 20 mg orally three times daily. CONCLUSIONS: Outbreaks of severe coagulopathies in users of synthetic cannabinoids adulterated with a long-acting anticoagulant continue to erupt in different regions of the world. Rapid recognition of an outbreak requires a high index of suspicion when confronting young, otherwise healthy subjects with otherwise unexplained severe coagulopathy.

Trace analysis of urea nitrate in post-blast debris by GC/MS.

Urea nitrate (uronium nitrate, UN) is an improvised explosive that looks very much like sugar and is easily made from accessible starting materials, urea and nitric acid. During the last decade it has been frequently used by terrorists in the Israeli arena and in other countries as well. It is difficult to identify urea nitrate in post-explosion debris, since only a very small fraction survives the blast. Also, in the presence of water, it readily decomposes to its original components, urea and nitric acid, two ubiquitous substances with relatively low evidential value. By further modifying McCord's recent version of Clark's method for the detection of minute amounts of urea, we were able to identify with high degree of certainty traces of uronium ion, the main characteristic factor of urea nitrate, in post-blast residues by GC/MS. The analytical process is based on the initial formation of xanthenyl urea by the reaction of uronium cation with xanthydrol, followed by reaction with alcohol to form xanthylurethane, which is readily identified by GC/MS. The reaction mechanism was corroborated by the use of labeled (15)N-urea. By applying the technique to residues collected from scenes of controlled firing experiments, 4 out of 16 samples showed the presence of uronium cation as indicated by the formation of the corresponding xanthylurethane. Potential interferences such as urea and ammonium nitrate did not respond under standard conditions. However, under strongly acidic conditions (pH<2), urea is converted into uronium ion, which is a nuisance, since it behaves as an authentic uronium cation. Such conditions, however, do not prevail at common crime scenes.