LONG ACTING ANTICOAGULANT RODENTICIDES

A report was recently forwarded to us by Dr. Charles McCune of Indianapolis of a dog taken to a practitioner after known ingestion of an anticoagulantrodenticide. The dog was treated, as is accepted practice, by the practitioner with injectable vitamin K and released. Ten days later the dog developed massive hemorrhages and was taken to Dr. McCune. In spite of supportive treatment and additional vitamin K therapy, the dog died. The purpose of this report is to emphasize the fact

that single treatment of toxicity of some of the second generation anticoagulants may be inadequate. The dose of vitamin K and the duration of treatment depends on the type of anticoagulant ingested and the response of the individual animal. The following article by the toxicology staff of ADDL addresses some of the issues of long acting and increased potency anticoagulant toxicosis.

Ingestion of anticoagulant rodenticidescontinues to be a common cause of poisoning in small animals. All of these anticoagulants act by interfering with the vitamin K enzyme complex, which is responsible for the production of functional clotting factors II, VII, IX, and X. Following ingestion, the onset of clinical signs is dependent on the amount ingested, the type of rodenticide, exposure to other drugs with high protein binding, individual animal variation, and the depletion of existing amounts of the affected clotting factors. The amounts of clotting factors II, VII, IX, and X decrease at rates similar to their half-lives which range from 6.2 to 41 hours in the dog. Clinical signs relating to a generalized coagulopathy and hemorrhage usually appear in one to five days although with internal bleeding the signs may go unnoticed until later.

It is important to remember that several types of anticoagulant rodenticides are in common use. These vary in the amount needed to cause poisoning, and the duration of effect (which is directly related to the duration of treatment).  The  older,  first  generation anticoagulants, the coumarins (warfarin and fumarin),   and   pindone   and   valone (indanediones),   usually   require   multiple ingestions and depress the amounts of clotting factors for seven to ten days. However, the second generation coumarins, brodifacoum and bromadiolone,    and   the   indanediones, diphacinone and chlorophacinone, are long-acting and will depress the amounts of clotting factors for three to four weeks. In addition, they generally only require a single ingestion of the anticoagulant-containing bait. Diagnosis is based on history of ingestion and/or access to an anticoagulant, clinical signs relating to hemorrhage,  and the  results of blood coagulation testing.

Treatment for all anticoagulant rodenticidetoxicoses is vitamin Kl with symptomatic and supportive treatment. Vitamin Kl itself has no direct effect on coagulation. Synthesis of new clotting factors requires six to 12 hours during which the animal may require supportive therapy such as blood transfusions. The dose of vitamin Kl and the duration of treatment depend on the type of anticoagulant ingested and the response of the individual animal. Pindone, valone, and the first generation coumarins (such as warfarin) may only require a dose of vitamin Kl at 1 ing/kg for five to seven days followed by re-evaluation of the coagulation status and continued therapy if indicated.    However,    the    long-acting anticoagulants, brodifacoum,bromadiolone, diphacinone, and chlorophacinone require 2.5 to 5.0 mg vitamin Kl/kg for three to four weeks followed by re-evaluation of the coagulation status and possible continuation of vitamin Kl therapy. More detailed discussions of the mechanisms,  diagnosis,  and therapy of anticoagulant rodenticide poisoning can be found in the references.

SUMMARY: Animals can be poisoned by short-acting or long-acting anticoagulant rodenticides.    Clinical signs relating to hemorrhage can appear in approximately one to five days. Diagnosis is based on history, clinical signs and results of blood coagulation tests. Treatment consists of symptomatic and supportive therapy and vitamin Kl at a dose and for a duration of time based on the type of anticoagulant ingested and the response of the patient

REFERENCES:

Dorman, David C. Anticoagulant, cholecalciferol, and bromethalin-based rodenticides. In, Veterinary Clinics of North America: Small Animal Practice, Beasley, Val Richard, ed.W.B.Saunders Co, Philadelphia, pp. 339-352, 1990.

Mount, M.E., Woody, B.J., and Murphy, M.J. The anticoagulant rodenticides. In, Current Veterinary Therapy DC, Small Animal Practice, R.W, Kirk, ed. W.B. Saunders Co., Philadelphia, pp. 156-165, 1986.

- ADDL Toxicology Personnel:

Christina Wilson, Laboratory Technician
Jennifer McCarthy, Assistant Chemist
Robert Everson,PhD, Analytical Chemist,

Laboratory Supervisor Stephen B.Hooser,DVM, PhD, Veterinary

Toxicologist, Section Head