Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment courses averaged 168 days. Adjunctive hemostatic therapy with recombinant factor VIIa and prothrombin complex concentrate has been reported, and phenobarbital has been used to expedite LAAR metabolism.

[Warfarin - its synthesis and properties in a twenty-year retrospective*]. / Warfarín - jeho syntéza a vlastnosti v dvadsatrocnej retrospektíve*

The review paper deals with some aspects of warfarin history and its use, at the beginning as a rodenticide and later as an anticoagulant. It describes its principal physical-chemical properties and it analyzes schematically the possibilities of its preparation by both selective and non-selective synthesis from coumarin derivatives. A survey of syntheses and its results are tabulated, including the literary references, and the paper is concluded with an evaluation of the prospects of this agent in comparison with alternative anticoagulants and its advantages, disadvantages and prospects.

Wartime rat control, rodent ecology, and the rise and fall of chemical rodenticides.

The story of how World War II stimulated the development of DDT, and the ensuing postwar dependence on such chemical insecticides, is well known. However, less recognition has been given to the wartime efforts to synthesize new rodenticides to fight rat-borne epidemics. Baltimore, Maryland served as the site for field tests of the powerful new compound alpha naphthyl thiourea (ANTU) from 1942-1946. This experimental campaign sparked debates over the efficacy of controlling rats via chemical warfare instead of environmental sanitation, which led to the ironic conclusion that urban rat control demanded an ecological, rather than technological, approach.