ACCORDING to the Veterinary Poisons Information Service (VPIS), well over 1,000 telephone enquiries are received each year from UK veterinary professionals seeking advice on how to manage potential and accidental exposures to anticoagulant rodenticides in a variety of animals – mainly pet dogs. Therapy is often complicated by uncertainty over the likelihood of exposure, the time that has elapsed since the anticoagulant was consumed and the dose ingested. The availability of appropriate treatments has also proved problematic until quite recently.
Anticoagulants
There are over 500 types of anticoagulant rodent poisons in use across Europe. Concentrates are generally reserved for professional use but coated cereals, bait blocks, baited traps, waxed “scatter packs”, sachets and semolina formats are freely available with some even boasting “professional strength” formulas. First generation anticoagulants include coumafen (warfarin) and coumatetralyl. These usually require higher doses to be consumed and repeated consumption over consecutive days is necessary to exert toxic effects in rodents. Second generation anticoagulants include diphacinone, difenacoum and bromadiolone and third generation products include brodifacoum and ocoumafen. These so called “superwarfarins” persist in the body for some time – up to eight weeks or longer in the case of the third generation compounds. Coumatetralyl was demonstrated to have a plasma elimination half-life of 0.52 days following a single oral dose compared to Brodifacoum, a secondgeneration product, which showed a plasma elimination half-life of 91.7 days.1 The elimination half-lives in liver varied from 15.8 days for coumatetralyl to 307.4 days for brodifacoum.
Anti-vitamin K1 action
Vitamin K1 is supplied through dietary intake and production by gut bacteria. It is needed to activate K-dependent coagulation factors prothrombin (II), proconvertin (VII), antihaemophilic factor B (IX) and Stuart factor (X). These factors are present in a nonfunctional form and are converted by active vitamin K1 into functional coagulants. In the process, vitamin K1 is converted into a non-active vitamin K1 epoxide. Active vitamin K1 is regenerated under normal conditions but anti-vitamin K1 anticoagulants interfere with this process. This means that the clotting factors remain in the non-functional state, leading to a high risk of haemorrhage. The effects remain as long as anticoagulant is present in the body and a significant intake of Vitamin K1 is needed to restore normal clotting during that time.
Clinical signs
Onset of clinical signs can take anywhere between one and 12 days (average 3-4 days) after ingestion of the anticoagulant. This can make diagnosis difficult. The signs include haemorrhages in various locations – nose, gingival tissues and eyes. Haematomas, haematuria or haemorrhagic diarrhoea, lethargy, depression, dyspnoea, anaemia, hypothermia, anorexia, blindness,
paresis, paralysis and seizures may be observed. There is likely to be an increase in prothrombin time (> 10 seconds), in partial thromboplastin time (PTT) and clotting time (> 10 minutes).
Vitamin K1 treatment
Vitamin K1 must be administered, as vitamin K3 is ineffective in anticoagulant poisoning. Some human preparations cannot be given intravenously as they are oil-based and may trigger an anaphylactic reaction. Subcutaneous and intramuscular routes are not generally recommended due to the risk of haematoma and poor resorption rates. A veterinary licensed Vitamin K1 (Vitamin K1 TVM, Eurovet Animal Health) has been introduced to the UK recently and can be given by slow iv injection, ensuring immediate 100% bioavailability and activation of the clotting factors to stop or reduce
active haemorrhages. Two doses should be given at 12 hour intervals at a dose rate of 5mg/kg (depending on the preparation used – always check manufacturer’s instructions). Supportive fluid therapy or blood transfusion may also be required. Injectable vitamin K1 should be followed by oral treatment with vitamin K tablets (5mg/kg daily), which need to be continued for the duration of time that the anticoagulant remains present in the body. Recent supply problems that have affected the availability of Vitamin K1 tablets will shortly be resolved by a veterinary licensed tablet. Oral doses should be given once daily, with a meal. Where the anticoagulant has not been identified, a minimum treatment period of 21 days is recommended. First generation anticoagulants will remain in the body for around 1-2 weeks, second generation for 2-3 weeks and third generation for 3-8 weeks. After 48 hours following cessation of oral treatment, the prothrombin time or clotting time should be evaluated. If prothrombin time extends beyond 10 seconds or clotting time is longer than 10 minutes, oral vitamin K1 should be continued for another week and the process repeated again at the end of that time.
- Vandenbroucke, V., Bousquet- Melou, A., De Backer, P. and Croubelsm, S. (2008) Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration. J. Vet. Pharmacol. Ther. 31 (5): 437-45.
