The elimination half-life of brodifacoum reportedly ranges from 16 to 36 days, with case reports of up to 270 days in intentional chronic exposures.^6,7 Treatment with vitamin K1 provides active cofactor, bypassing the inhibited enzymes. However, considering the lack of regeneration of spent cofactor to vitamin K1, poor oral absorption of vitamin K1, and the long elimination half-life of many superwarfarins, patients must take regular large doses of vitamin K1 for a prolonged course to continue to produce clotting factors.

Diagnosis and Treatment

Suspect brodifacoum in patients presenting with unexplained bleeding, particularly hematuria and flank pain. Because brodifacoum is a superwarfarin, patients will present with a markedly elevated prothrombin time and INR. A history of synthetic cannabinoid or other illicit substance use may strongly support the diagnosis, especially in the setting of a cluster of cases. A thorough history addressing other causes of genetic or acquired coagulopathy is vital. Calling your local poison center may prove crucial in facilitating initial stabilization, long-term management, and coordination with the local health department.

Faced with a large-scale outbreak and the need to properly utilize available resources, we developed a treatment protocol that started with 10 mg of IV vitamin K1 and Kcentra, FFP, or factor eight inhibitor bypassing activity (FEIBA) for major bleeding. All patients who could tolerate oral delivery without active gastrointestinal bleeding were also started on oral vitamin K1 at 50 mg three times a day and then titrated every 48 hours to maintain an INR below 2.

Once patients were on a stable minimum dose, they were discharged. Every patient required reliable outpatient follow-up and access to vitamin K, which was complicated by the cost of vitamin K1, the large doses required, and the anticipated prolonged duration of treatment.

Complete the CME activity.

Dr. Rasin is a toxicology fellow at Toxikon Consortium in Chicago.

Dr. Devgun is a clinical instructor and attending at the University of Illinois at Chicago.

Dr. Kim is an attending physician at NorthShore University HealthSystem in Evanston, Illinois.

References

1. King N, Tran MH. Long-acting anticoagulant rodenticide (superwarfarin) poisoning: a review of its historical development, epidemiology, and clinical management. Transfus Med Rev. 2015;29(4):250-258.
2. Moritz E, Austin C, Wahl M, et al. Notes from the field: outbreak of severe illness linked to the vitamin K antagonist brodifacoum and use of synthetic cannabinoids – Illinois, March-April 2018. MMWR Morb Mortal Wkly Rep. 2018;67(21):607-608.
3. Waien SA, Hayes D Jr, Leonardo JM. Severe coagulopathy as a consequence of smoking crack cocaine laced with rodenticide. N Engl J Med. 2001 30;345(9):700-701.
4. Spahr JE, Maul JS, Rodgers GM. Superwarfarin poisoning: a report of two cases and review of the literature. Am J Hematol. 2007;82(7):656-660.
5. Miller ME. Inside Alabama’s deadly spice craze. The Washington Post. April 24, 2015.
6. Weitzel JN, Sadowski JA, Furie BC, et al. Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum: clinical and metabolic studies of three cases. Blood. 1990;76(12):2555-2559.
7. Babcock J, Hartman K, Pedersen A, et al. Rodenticide-induced coagulopathy in a young child. A case of Munchausen syndrome by proxy. Am J Pediatr Hematol Oncol. 1993;15(1):126-130.