Surreptitious Ingestion of a Long-Acting Vitamin K Antagonist/Rodenticide, Brodifacoum: Clinical and Metabolic Studies of Three Cases

The vitamin K metabolism of three patients with factitious purpura due to brodifacoum ingestion was studied. These patients, who presented with bleeding disorders due to deficiency of the vitamin K-dependent blood clotting proteins, were refractory to vitamin K, at standard doses and required fresh frozen plasma to control bleeding until large doses of vitamin K, were used. Metabolic studies demonstrated a blockade in vitamin K utilization, consistent with the presence of a vitamin K antagonist, but the patients denied use of anticoagulants. Warfarin assays were negative. We show that the factitious purpura in each patient was due to the surreptitious ingestion of brodifacoum. a OAGULOPATHIES due to severe deficiency of the C vitamin K-dependent blood coagulation proteins are associated with deficiency of vitamin K and ingestion of vitamin K antagonists, such as the anticoagulant warfarin sodium. The vitamin K-dependent blood proteins are synthesized in the liver in a precursor form.’ In a reaction directed by the y-carboxylation recognition site on the propeptide of the vitamin K-dependent proteins,293 a hepatic vitamin K-dependent carboxylase converts glutamic acid residues near the amino-terminus of these proteins to y-carboxyglutamic acid. The conversion of vitamin K, hydroquinone to vitamin KI-2,3-epoxide is closely coupled to the carboxylation of glutamic acid. The vitamin K epoxide reductase converts the vitamin K epoxide to vitamin K, and the vitamin K reductase reduces vitamin K to its active hydroquinone form. Coumarin anticoagulants, such as warfarin, inhibit the vitamin K epoxide reductase, resulting in accumulation of vitamin K ep~xide.~ Synthesized in the presence of warfarin, the vitamin K-dependent proteins are deficient in y-carboxyglutamic acid and cannot assume a metal-stabilized conformation required for protein-membrane interaction and biologic activity. Taken in excess by accidental ingestion or overdosage, vitamin K antagonists can be associated with severe bleeding. In factitious purpura, warfarin is used surreptitiously as a manifestation of an underlying psychiatric disorder.’ In the absence of anticoagulant therapy or mahbsorption syndromes, an acquired bleeding disorder associated with specific deficiency of all of the vitamin K-dependent blood coagulation proteins is due to the accidental or factitious ingestion of vitamin K antagonists. Because warfarin has been the dominant vitamin K antagonist available as an anticoagulant and as a rodenticide in North America, establishing the presence of warfarin in the serum of such a patient confirms the diagnosis. In the current report, we describe three patients with severe bleeding disorders due to deficiency of the vitamin K-dependent blood clotting proteins and without detectable serum warfarin. We show that all three cases of factitious purpura were due to the ingestion of brodifacoum, a second generation long-acting vitamin K antagonist used as a rodenticide. The coagulopathies responded to long-term administration of high-dose vitamin K, therapy. potent second generation long-acting vitamin K antagonist used as a rodenticide. The coagulopathies responded to long-term therapy with large doses of vitamin K,. The serum elimination half-time for brodifacoum ranged from 16 to 36 days in these patients. The anticoagulant effect is of long duration, requiring chronic vitamin K treatment. With increasing availability of new rodenticides, factitious purpura due to surreptitious ingestion of these potent vitamin K antagonists is emerging as a new problem, previously associated with warfarin, with important implications for diagnosis and treatment.