Superwarfarin contaminants found in synthetic cannabinoid-associated coagulopathy outbreak

1. During one month at a single medical center in Illinois in 2018, 34 cases of synthetic cannabinoid associated coagulopathy were identified.

2. Of the 15 patients who underwent anticoagulant poisoning testing, all 15 were positive for brodifacoum.

Evidence Rating Level: 4 (Below Average)        

Study Rundown: Synthetic cannabinoids are produced to mimic the user experience of cannabinoids while also being difficult to detect by traditional drug screening methods. Adverse effects of synthetic cannabinoids include intracranial hemorrhage, though coagulopathy has not previously been identified. Multiple patients presented to Illinois hospitals in 2018 with severe bleeding and public health officials linked the grouped presentations to synthetic cannabinoids. This case series examines the patient presentations and treatments of patients treated at a single institution during this outbreak. Out of 45 hospitalizations, 34 patients met criteria for synthetic cannabinoid-associated coagulopathy. Gross hematuria and abdominal pain were the most common bleeding and non-bleeding symptoms, respectively. Anticoagulant testing on 15 patients showed all 15 patients were positive for brodifacoum.

Strengths of this study include a notable proportion of patients identified in the statewide outbreak presented to the institution conducting the study and anticoagulant testing identifying coagulopathy causative agents. Limitations include its case series design and limited description of patient management.

Click to read the study in NEJM

Relevant Reading: Hemorrhagic stroke following use of the synthetic marijuana “spice”

In-Depth [case series]: This case series describes 34 patients who presented to a single institution during a synthetic cannabinoid-associated coagulopathy outbreak from March to April 2018, and includes a total of 45 hospitalizations. Eligible patients were diagnosed with synthetic cannabinoid-associated coagulopathy using institutional criteria. Anticoagulant testing was performed on a subset of 15 patients. At presentation the most common bleeding symptoms were gross hematuria, bruising, and melena, and the most common non-bleeding symptoms were abdominal pain, flank pain, and nausea/vomiting. The mean international normalized ratio (INR) was 15.8. Median number of days since last use of synthetic cannabinoid was 1 (range 1-3 days). Anemia was present in 29% of hospitalizations and leukocytosis was present in 53% of hospitalizations. For patients who underwent CT imaging for abdominal or flank pain, 12 of 23 patients had radiographic renal abnormalities. Confirmatory anticoagulant testing was performed in 15 patients with brodifacoum found in 15 patients, dif­enacoum in 5, bromodiolone in 2, and warfarin in 1 patient. Management varied by patient, but treatment strategies included oral vitamin K, intravenous vitamin K, red-cell transfusion, fresh frozen plasma transfusion, and 4-factor prothrombin complex concentrate. All patients, except for one patient who died during hospitalization, resulted in cessation of bleeding.

Image: PD

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