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Ann N Y Acad Sci. 2016 Jun;1374(1):111-22. doi: 10.1111/nyas.13085. Epub 2016 May 31.

The emerging threat of superwarfarins: history, detection, mechanisms, and countermeasures.

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Department of Anesthesiology, University of Illinois, Chicago, Illinois.
Jesse Brown VA Medical Center, Chicago, Illinois.
Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, North Carolina.
Department of Medicine, University of Illinois, Chicago, Illinois.
Department of Pathology, the Ohio State University, Columbus, Ohio.
Department of Physics and the Center for the Molecular Study of Condensed Soft Matter, Illinois Institute of Technology, Chicago, Illinois.
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, Illinois.
X-ray Science Division, Argonne National Laboratory, Lemont, Illinois.


Superwarfarins were developed following the emergence of warfarin resistance in rodents. Compared to warfarin, superwarfarins have much longer half-lives and stronger affinity to vitamin K epoxide reductase and therefore can cause death in warfarin-resistant rodents. By the mid-1970s, the superwarfarins brodifacoum and difenacoum were the most widely used rodenticides throughout the world. Unfortunately, increased use was accompanied by a rise in accidental poisonings, reaching >16,000 per year in the United States. Risk of exposure has become a concern since large quantities, up to hundreds of kilograms of rodent bait, are applied by aerial dispersion over regions with rodent infestations. Reports of intentional use of superwarfarins in civilian and military scenarios raise the specter of larger incidents or mass casualties. Unlike warfarin overdose, for which 1-2 days of treatment with vitamin K is effective, treatment of superwarfarin poisoning with vitamin K is limited by extremely high cost and can require daily treatment for a year or longer. Furthermore, superwarfarins have actions that are independent of their anticoagulant effects, including both vitamin K-dependent and -independent effects, which are not mitigated by vitamin K therapy. In this review, we summarize superwarfarin development, biology and pathophysiology, their threat as weapons, and possible therapeutic approaches.


HPLC; brodifacoum; intralipid; lipid membrane; nephrotoxicity; neuropathology; superwarfarins

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