Combined Superwarfarin and Ethylene Glycol Ingestion: A Unique Case Report With Misleading Clinical History

1995 
A markedly elevated prothrombin time (PI) and activated partial thromboplastin time (AFIT) were observed in a 24-year-old man who was admitted with a history of ethylene glycol ingestion. Further laboratory evaluation suggested that the coagulopathy was related to acquired factor deficiencies. The PI' and A FI T improved transiently on usual doses of vitamin K, but rapidly became abnormal again. The coagulopathy was controlled only after large doses of vitamin K for at least 37 days. On further questioning, the patient admitted to consuming a large quantity of a rodenticide. The second generation anticoagulant rodenticides (superwarfarins) result in a potent and prolonged anticoagulant effect by reducing the activity of the vitamin K dependent factors (II, XII, IX, and X). To our knowledge, this is the first reported concomitant ingestion of both ethylene glycol and a superwarfarin compound. This case serves to illustrate how a logical laboratory evaluation can lead to the proper diagnosis, despite a misleading clinical history. (Key words: Superwarfarin; Ethylene glycol; Brodifacoum; Rodenticide; Anticoagulants) Am J Clin Pathol 1995; 104:663-666. Due to the development of warfarin (3-a-acetonylbenzyl)-4-hydroxy-coumarin) resistance in mice and rats, a group of potent new rodenticides has been developed including difenacoum, bromadiolone, and brodifacoum, which are 4-hydroxy-coumarin derivatives, and diphacinone, pindone, and chlophacinone, which are inandione derivatives. These compounds, aptly named "superwarfarins," cause a decrease in gamma-carboxylation of glutamic acid residues of coagulation factors II, VII, IX, and X, which is 100-fold greater than that caused by warfarin'- 2 and results in dysfunctional but detectable forms of these factors. The half-life of the superwarfarins is much greater than that of warfarin. In rats, the serum half-life of brodifacoum is 156 hours, 3 compared to a plasma half-life of 37 ± 15 hours for warfarin. 4 The half-life of the superwarfarins in humans is unknown. Products containing these second generation anticoagulant compounds (D-con, Havoc, Talon-G) are available in overthe-counter rodenticides and may result in accidental or intentional human ingestion. The extremely long half
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