Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum: clinical and metabolic studies of three cases

Abstract

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 K1 at standard doses and required fresh frozen plasma to control bleeding until large doses of vitamin K1 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 potent second generation long-acting vitamin K antagonist used as a rodenticide. The coagulopathies responded to long-term therapy with large doses of vitamin K1. 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.

The long‐term effects of the rodenticide, brodifacoum, on blood coagulation and vitamin K metabolism in rats

“…Poisoning, intentional or accidental, with these rodenticides has been reported (Park et al, 1986;Greeff et al, 1987; 1 Author for correspondence. Weitzel et al, 1990). Vitamin K is the physiological antidote.…”

Successful liver transplantation from a donor with brodifacoum intoxication

“…3,9,10 Therefore, the importance of long-term prophylaxis for coagulopathy with vitamin K has been stressed. 2,7 Because there was no previous report of organ transplantation from a donor with brodifacoum intoxication, we were unable to estimate the risk for transmission of coagulopathy from the donor to the recipient in this case. Toxicologists advised us that brodifacoum does not cause liver damage, and coagulopathy can be controlled with careful monitoring of the PT and administration of high-dose vitamin K (personal communication, poison control center, November 1997).…”

“…Its anticoagulant effect, however, is more potent and prolonged than that of warfarin. 1,2 Patients with severe brodifacoum intoxication present with spontaneous hemorrhage from multiple organs and require long-term administration of vitamin K. [2][3][4][5][6][7] In the United States each year, more than 120,000 cases of poisoning occur with brodifacoum or similar agents, and there have been three reported deaths related to brodifacoum intoxication (Rose Ann Soloway, American Association of Poison Control Centers, personal communication, July 1999).…”

Superwarfarin poisoning: A report of two cases and review of the literature

“…The elimination half-life in rats is 156 hr compared to the 17-hr half-life of warfarin [6]. In humans, the half-life is between 243À1656 hr for brodifacoum [7,8], compared to 17-37 hr for warfarin. The clearance follows zero-order kinetics initially, but converts to first-order kinetics at lower concentrations [6,9].…”