Brodifacoum poisoning: A clear and present danger to public health in the USA

Feinstein, Douglas L.; Brodsky, Sergey V.; Weinberg, Guy; Breeman, Richard van; Rubinstein, Israel

doi:10.1016/j.toxlet.2017.01.004

Cited by 19 publications

(8 citation statements)

References 12 publications

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“…We could not monitor quantitative levels of brodifacoum, as we believed our approach using basic coagulation screening and in-clinic verification of oral vitamin K1 treatment adequately treated the patient's brodifacoum exposure. Given that the rodenticide exposure is still high with an incidence of over 8,000 cases in 2012, we hope that our case report in this clinical scenario will help to increase awareness of this public health issue [10,11].…”

Section: Discussionmentioning

confidence: 91%

Superwarfarin Exposure: An Important Uncommon Cause of Painless Bleeding

et al. 2019

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Painless bleeding in a patient presenting from the community with elevated coagulation studies rarely makes the physicians suspect superwarfarin or rodenticide poisoning. Although a significant number of superwarfarin exposure cases are diagnosed every year, we believe there appears to be delay in diagnosis and confusion in determining what is the ideal way to treat and monitor these patients during the management. This is the first thorough literature review of all the reported cases of superwarfarin poisoning which also studied the clinical presentation, management and follow-up patterns. We present a 70-year-old man who presented to the emergency room with epistaxis, melena, colacolored urine with elevated prothrombin time (PT), activated partial thromboplastin time (aPTT) and international normalized ratio (INR). Mixing studies showed complete correction of coagulopathy indicative of factor deficiency. Additional history revealed that the patient had arguments with family member at home and made us suspect superwarfarin exposure. Qualitative brodifacoum testing was positive and was managed with fresh frozen plasma and high doses of vitamin K1 (phytomenadione) with serial monitoring of INR and clinical symptoms. Superwarfarin poisoning should be considered in the differential diagnosis of a patient who presents with above clinical and laboratory profile especially in the absence of any history of coagulopathy or anticoagulant use. We want to raise public and especially physician awareness that history taking, early diagnosis and managing in right clinical setting play a significant role in survival of these patients.

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Section: Discussionmentioning

confidence: 91%

Superwarfarin Exposure: An Important Uncommon Cause of Painless Bleeding

et al. 2019

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“…3 Exposure to LAARs can occur through different routes, including ingestion, inhalation, and transcutaneous exposure. 3 Large-scale poisoning attempts with brodifacoum 15 have also raised serious public health concerns surrounding intentional misuse. Because of the commercial availability of brodifacoum, the variety of routes with which individuals can be exposed to drug, and the delayed manifestations of symptoms after poisoning, the US government lists brodifacoum on the chemical threat risk assessment compound list.…”

Section: Laarsmentioning

confidence: 99%

“…Because of the commercial availability of brodifacoum, the variety of routes with which individuals can be exposed to drug, and the delayed manifestations of symptoms after poisoning, the US government lists brodifacoum on the chemical threat risk assessment compound list. 15 Brodifacoum consists of a substituted phenyl chain for the terminal methyl group of warfarin, which accounts for its high affinity for vitamin K epoxide reductase, resulting in a 40-to 50-fold increase in hepatic concentration and 100-fold increase in potency relative to warfarin (Figure 1). [16][17][18] Pharmacokinetic studies in rabbits 19 and poisoning cases in humans 20 indicate a high volume of distribution and a biexponential decay caused by slow plasma clearance.…”

Section: Laarsmentioning

confidence: 99%

Bad weed: synthetic cannabinoid–associated coagulopathy

Arepally

Ortel

2019

Blood

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Recent multistate outbreaks of coagulopathy caused by brodifacoum-tainted synthetic cannabinoids or “fake weed” highlight the public health impact of long-acting anticoagulant rodenticides (LAARs). Patients presenting with this syndrome have had recent exposure to synthetic cannabinoids, evidence of isolated vitamin K antagonism with or without bleeding, and detectable levels of brodifacoum and other LAARs in circulation. This article will provide information on synthetic cannabinoids, LAARs, and coagulopathic manifestations arising from use of adulterated synthetic cannabinoids and their management.

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“…These properties result in extremely low median lethal dose (LD 50 ) values, typically between 0.2 and 0.8 mg/kg in rodents, and an acute lethal dose in humans of approximately 15 mg/kg (Table 1 ). LAARs are used worldwide to eradicate rodent infestations; however, unfortunately, their increased use has led to increased incidence of accidental poisonings, primarily in children, and unintentional exposure following accidental leakage [ 4 ]. In the majority of these cases, a single administration of fresh frozen plasma or vitamin K1 can restore coagulation to normal levels within a relatively short period; however, following ingestion of larger amounts, as often occurs in suicide attempts, daily administration of vitamin K1 is required for months to over 1 year [ 5 ], the time needed for serum LAAR levels to diminish to levels considered non-toxic (< 10 ng/ml) [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Should Cytochrome P450 Inducers be Used to Accelerate Clearance of Brodifacoum from Poisoned Patients?

et al. 2019

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A recent multi-state outbreak of life-threatening bleeding following inhalation of synthetic cannabinoids has been attributed to contamination with the long-acting anticoagulant rodenticide (LAAR) brodifacoum, a second-generation, highly potent, long-acting derivative of the commonly used blood thinner warfarin. While long-term treatment with high-dose vitamin K1 restores coagulation, it does not affect brodifacoum metabolism or clearance, and, consequently, brodifacoum remains in the human body for several months, thereby predisposing to risk of bleeding recurrence and development of coagulation-independent injury in extrahepatic tissues and fetuses. This has prompted the evaluation of pharmacological measures that accelerate brodifacoum clearance from poisoned patients. Since the induction of certain cytochrome P450 (CYP) enzymes accelerates warfarin metabolism, using CYP inducers, such as phenobarbital, to accelerate brodifacoum clearance seems plausible. However, unlike warfarin, brodifacoum does not undergo significant metabolism in the liver, nor have the effects of phenobarbital on vitamin K1 metabolism been previously determined. In addition, the safety of phenobarbital in brodifacoum-poisoned patients has not been established. Therefore, we propose that CYP inducers should not be used to accelerate the clearance of brodifacoum from poisoned patients, but that alternative approaches such as reducing enterohepatic recirculation of brodifacoum, or using lipid emulsions to scavenge brodifacoum throughout the body, be considered.

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Brodifacoum poisoning: A clear and present danger to public health in the USA

Cited by 19 publications

References 12 publications

Superwarfarin Exposure: An Important Uncommon Cause of Painless Bleeding

Superwarfarin Exposure: An Important Uncommon Cause of Painless Bleeding

Bad weed: synthetic cannabinoid–associated coagulopathy

Should Cytochrome P450 Inducers be Used to Accelerate Clearance of Brodifacoum from Poisoned Patients?

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