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The emerging threat of superwarfarins: history, detection, mechanisms, and countermeasures
Author(s) -
Feinstein Douglas L.,
Akpa Belinda S.,
Ayee Manuela A.,
Boullerne Anne I.,
Braun David,
Brodsky Sergey V.,
Gidalevitz David,
Hauck Zane,
Kalinin Sergey,
Kowal Kathy,
Kuzmenko Ivan,
Lis Kinga,
Marangoni Natalia,
Martynowycz Michael W.,
Rubinstein Israel,
Breemen Richard,
Ware Kyle,
Weinberg Guy
Publication year - 2016
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.13085
Subject(s) - brodifacoum , warfarin , vitamin k epoxide reductase , vitamin , vitamin k , rodenticide , toxicology , rodent , accidental , medicine , intensive care medicine , environmental health , pharmacology , biology , ecology , cyp2c9 , physics , cytochrome p450 , metabolism , acoustics , atrial fibrillation
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.