POISON CONTROL
BRODIFACOUM POISONING:
A New Risk in the Use of Synthetic Cannabinoids By Kristen C. Lee, PharmD, BCPS Clinical Toxicology/EM Fellow at Florida/USVI Poison Information Center—Jacksonville
By Madison Schwartz, PharmD Clinical Toxicology/EM Fellow at Florida/USVI Poison Information Center—Jacksonville
A 27-year-old female presents to the emergency department complaining of increased bruising over the past few weeks and dark stool for the last three days. She has no prior medical history and is not on any prescription or overthe-counter medications. Her vital signs are within normal limits. Her urine drug screen is positive for cocaine and THC. Initial coagulation studies reveal an INR of 8.5 and a PTT of 85.7 sec. Upon further questioning, the patient admits to “occasional” cocaine use, as well as “intermittent” use of synthetic cannabinoid products that may include K2 or Spice. What is the connection between the patient’s use of synthetic cannabinoids and her current presentation? Synthetic cannabinoids, including those sold under the names “K2” or “Spice,” are synthetically-derived compounds that agonize the cannabinoid receptor. In March 2018, the Illinois Poison Center alerted the Illinois Department of Public Health to a series of cases of patients presenting to emergency departments with unexplained bleeding, elevated INRs from 5 to >20 and recent use of synthetic cannabinoids. Blood samples in subsequent cases seen throughout the U.S. were found to be positive for brodifacoum.1 Brodifacoum is a long-acting anticoagulant rodenticide (LAAR) in the same pharmacologic class as warfarin, with a chemical structure differentiated by a longer polycyclic hydrocarbon side chain. Brodifacoum is considered a “superwarfarin” because, like warfarin, it blocks formation of the active form of vitamin K to inhibit production of clotting factors II, VII, IX and X. However, its high lipid solubility and ability to concentrate heavily in the liver confers activity 100 times that of warfarin, with a longer duration of action.2 The terminal elimination half-life of brodifacoum in human cases has ranged from 24 to 31 days.3, 4 In animal models, brodifacoum has demonstrated a half-life of up to 120 days.5 Patients who present with signs or symptoms of bleeding— including hematemesis, hemoptysis, bruising, epistaxis, unusually heavy menstrual bleeding, melena, hematuria, bleeding gums, or bleeding disproportionate to injury— should be questioned about use of synthetic cannabinoids including K2/Spice in the last three months. Laboratory diagnostics should include an INR ≥ 2 or an abnormal coagulation profile with no alternative clinical cause, or identification of an LAAR through high-performance liquid chro¬matography–tandem mass spectrometry of blood 34
samples.1 Life-threatening bleeds due to brodifacoum should be managed similarly to warfarin toxicity, with rapid reversal of anticoagulation using fresh frozen plasma (FFP), prothrombin complex (PCC) or recombinant factor VIIa.6 To sustain the INR reversal achieved by FFP or factor products, vitamin K 5-10 mg (up to 400 mg has been needed) should be administered intravenously.7 Slower infusions (i.e. 1 mg/min) may reduce the risk of anaphylactoid reactions. In patients with elevated INR in the absence of significant bleeding, intravenous vitamin K alone can be given at the above-mentioned dosages. Caution should be used in patients on an anticoagulant for medical reasons. Once INR reversal is achieved, vitamin K should be continued orally and can be treated on an outpatient basis with regular follow-up for laboratory assessment once coagulation abnormalities have stabilized. While dosing strategies are variable based on response, one approach is 25-50 mg PO vitamin K 3-4 times daily for 1-2 days, with regular INR monitoring for adjustment of dosing.7 Serial serum concentrations of brodifacoum may also be useful in guiding duration of therapy, but may require analysis by independent laboratories and take multiple days to result.8 Because of the long duration of action of brodifacoum, patients should be followed to the resolution of coagulopathy, which may require weeks to months of observation. Serial INR measurements may guide tapering of vitamin K.2 Cases of brodifacoum-tainted synthetic cannabinoids have
EMPULSE WINTER 2019
