Anticoagulant Rodenticide Toxicity

Also known as: Warfarin Toxicity, Anticoagulant Rodenticide Toxicity/ Poisoning.

Description

One of the most common causes of an acquired coagulopathy in dogs is the accidental ingestion of an anticoagulant rodenticide. The first generatlion coumarin-derivative anticoagulant, warfarin. has a short half-life of about 12 hours and a relatively low toxicity in non-target species. Therefore, repeated or massive exposure would generally be required to produce clinical bleeding in a dog. The second generation coumarin derivatives (bromadiolone and brodifacoum) and indandione rodenticides (pindone and diaphacinone), developed in response to wartarin resistance in target species, are tar more potent than warfarin. They have much longer lasting etfects (half-lives of four to six days) as they are more completely bound to plasmla proteins and, compared to warfarin, have an enhanced tendency to accumulate in hepatic tissue. Secondary poisoning through ingestion ol killed target species is more likely to occur with these latter agents. The coumarin derivatives exert interaction of their anticoagulant eftect by inhibiting the enzyme, vitamin K epoxide reductase (see box on page 63). This enizymiie is a component of the vitamin K epoxide cycle required tf)r hepatic synthesis of the functional clotting factors F-II, F-VII, F-IX and F-X. Inhibition of the enzyme causes the accumulation of the inactive vitamin K epoxide and prevents the carboxylation of vitamin K-dependent coagulation proteins. The acarboxy precursor proteins are incapable of being activated during the coagulation process and thus cannot actively participate in fibrin formation.

Signalment

• Most commonly seen in the dog and pig, after eating bait for rodents.
  • Warfarin poisoning is therefore relatively common in farm dogs.

Diagnosis

Clinical Signs

The diagnosis of anticoagulant rodenticide toxicosis is dependent on a thorough patient history and physical examination, and appropriate haemostatic testing. The likelihood of exposure to a specific rodenticide may be difficult to reliably determine. The onset of clinical signs is delayed for several days post-exposure while the plasma concentrations of the vitamin K-dependent clotting factors become depleted. Symptoms may be non-specific if there is internal bleeding, and might include depression, weakness, pallor, dyspnoea, abdominal swelling, or even sudden death. Other possible signs include anaemia, external haematomas, bruising, excessive bleeding from venepuncture sites or other sites of injury, epistaxis, haematemesis, haematochezia, melaena, haematuria and/or lameness.

Laboratory Tests

Coagulation screening tests are unlikely to reveal abnormalities until at least 36 to 72 hours post-exposure. The prothrombin time (PT) generally becomes prolonged first (by 36 to 48 hours), since F-VII, a component of the tissue factor-mediated coagulation pathway, has the shortest half-life (about six hours) and is therefore the first factor to become depleted. The partial thromboplastin time (PTT) and activated clotting time (ACT) are usually prolonged by 48 to 72 hours post-exposure. The thrombin clotting time (TCT), platelet count and buccal mucosal bleeding time (BMBT) (an assessment of platelet function) are usually normal (see table below). The so-called 'proteins induced by vitamin K antagonism' (PIVKA) are acarboxylated proteins formed as a result of anticoagulant rodenticide toxicity. While not normally detected in the circulation, these increase in the plasma of poisoned animals and can be detected using the PIVKA test which is available through some veterinary diagnostic laboratories. PIVKA are usually cleared within 12 hours of administration of vitamin K. Samples for coagulation testing should be collected before initiating vitamin K therapy. Other possible confirmatory tests include quantitation of vitamin K epoxide concentrations and determination of the specific anticoagulant in the blood, liver and/or stomach contents.

Pathology

• Gastric haemorrhage
• Haemorrhage elsewhere in body, particularly mediastinum

References

1. Beasley, V (1999) Toxicants that Interfere with the Function of Vitamin K. In Veterinary Toxicology, International Veterinary Information Service.
2. DeWilde, L (2007) Why is Fluffy Bleeding? Secondary Hemostatic Disorders. In Proceedings of the North American Veterinary Conference 2007, NAVC.
3. Dodds, W J (2005) Bleeding Disorders in Animals. In Proceedings of the World Small Animal Veterinary Association 2005, IVIS.
4. Murphy, M J and Talcott, P A (2005) Anticoagulant Rodenticides. In Small Animal Toxicology (Second Edition), Saunders.
5. Campbell, A (1999) Common causes of poisoning in small animals. In Practice, 21(5), 244-249.
6. Keen, P and Livingston, A (1983) Adverse reactions to drugs. In Practice, 5(5), 174-180.
7. Mayer, S (1990) Coumarin Derivatives. In Practice, 12(4), 174-175.
8. johnstone, I () Bleeding disorders in dogs 2. Acquired disorders. In Practice, 24(2), 62-68.