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Background
The discovery of vitamin K antagonists has its origins in poisoning. Fatal haemorrhagic disease in cattle following the ingestion of spoiled sweet clover was first described during the 1920s. 1 This was later linked to impaired prothrombin function 2 and subsequently a 4-hydroxycoumarin compound, named dicoumarol was identified as the agent responsible. 3 Synthesis of dicoumarol analogues led to the synthesis of warfarin, 4 which was successfully deployed as an anticoagulant rodenticide alongside other first generation vitamin K antagonists including coumarins such as coumachlor, coumatetralyl; and indandiones including diphacinone. In response to the appearance of resistance among rat populations, 5 6 long-acting warfarin derivatives; superwarfarins such as brodifacoum, bromodialone and difenacoum, were synthesised. In parallel to these developments warfarin was introduced as a therapeutic anticoagulant in humans used for prophylactic treatment of thomboembolic disease.
Vitamin K antagonists elicit their anticoagulant effect by inhibiting the action of vitamin K 2,3-epoxide reductase (VKOR), which is responsible for the conversion of the inactive vitamin K epoxide to the active hydroquinone form, which is then available as a cofactor for the [GAMMA]-carboxylation of vitamin K-dependent proteins by the enzyme vitamin K-dependent carboxylase. As a result of inhibition of this process, [GAMMA]-carboxylation of the hepatic vitamin K-dependent clotting factors II, VII, IX, X, is impaired, leading to inhibition of coagulation. 6 Vitamin K antagonists are also known to elicit a procoagulant effect and cases have been reported where patients exposed to superwarfarins present with thrombosis as well as bleeding, 7 which is likely to be related to the inhibition of the vitamin K-dependent anticoagulant proteins C and S. Although the majority of cases reported in the literature indicate bleeding is the most common complication of superwarfarin poisoning clinicians should be aware of this less common presentation.
Superwarfarins are highly potent, long-acting, vitamin K antagonists. The enhanced potency of superwarfarins is due to their greatly extended tissue half-lives, their lipophilic nature causing them to reside for long periods in the liver. 8 Exposure to these commonly available rodenticides can result in potentially fatal haemorrhage and less commonly thrombosis. 7 9 10 Acute life-threatening complications can be prevented with timely intervention. Immediate administration of fresh frozen plasma, 8 four factor prothrombin complex concentrate and/or phytomenadione (vitamin K1 ) can...