Superwarfarin ingestion and detection

Abstract

Because of the emergence of warfarin resistance, new potent long-acting anticoagulants are now readily available in several over-the-counter rodenticide products. The availability of these "superwarfarin" compounds has led to accidental and purposeful human ingestions, one of which has resulted in a death. We summarize the prior case reports and report a second death. In addition, we report the availability of an assay to detect the presence of brodifacoum (a superwarfarin compound) in human plasma and tissues.

Lethal paradoxical cerebral vein thrombosis due to suspicious anticoagulant rodenticide intoxication with chlorophacinone

“…Novel compounds were synthesized to combat rodent resistance, thereby creating a new class of anticoagulantsthe superwarfarins [10].…”

Superwarfarins

“…Serious poisoning has been reported in adults with massive overdoses. These long-acting anticoagulants have produced rapid and persistent bleeding due to hypoprothrombinemia (Chong et al, 1986;Hoffman et al, 1988;Katona and Wason, 1989;Wallace et al, 1990;Routh et al, 1991;Barnett et al, 1992;Exner et al, 1992;Mack, 1994;Morgan et al, 1996;McCarthy et al, 1997;Gallo, 1998;Berry et al, 2000). There is a risk of spontaneous abortion with long-acting anticoagulants (Lipton and Klass, 1984;Zurawski and Kelly, 1997;Nelson et al, 2006).…”

“…Newer long-acting warfarin derivatives such as brodifacoum, bromadiolone, diphenadione, and chlorophacinone can produce profound and prolonged anticoagulation and bleeding after a latency period that generally lasts 24-72 h FDA, 1985;Chong et al, 1986;Greeff et al, 1987;Smolinske et al, 1989;Swigar et al, 1990;Wallace et al, 1990;Routh et al, 1991;Wilton, 1991;Exner et al, 1992;Rauch et al, 1994;IPCS, 1995a-e;Hui et al, 1996;Tecimer and Yam, 1997;Chua and Friedenberg, 1998;Gallo, 1998;EPA, 2003EPA, , 2005 (Table 18.1).…”

“…For example, a bait concentration of only 50 ppm of brodifacoum is adequate to control the population in a single feeding for most rodents and noncommensal species (Matolesy et al, 1988). These newer compounds were called second-generation anticoagulant rodenticides and are often now referred to as superwarfarins in the contemporary medical literature (e.g., Chong et al, 1986;Greeff et al, 1987;Swigar et al, 1990;Wallace et al, 1990;Routh et al, 1991;Wilton, 1991;Exner et al, 1992;Rauch et al, 1994;Hui et al, 1996;Tecimer and Yam, 1997;Gallo, 1998;Chua and Friedenberg, 1998;Pavlu et al, 2005;Sharma and Bentley, 2005;Dolin et al, 2006).…”

Analysis of chiral pharmaceuticals using HPLC with CD detection

“…However, do not think that if you are on Coumadin/warfarin therapy that you can substitute rat poison; besides the impurities found in the warfarin used for that purpose, many other potentially fatal ingredients are used to enhance the effectiveness of the rodenticide, and none of these would be healthy to consume. 11 The chromatogram from the prescription Coumadin tablet is shown in Figure 5. No peaks are observed with the OR detector due to its decreased sensitivity in comparison to the CD chiral detector.…”