Anticoagulant rodenticides inhibit the enzyme vitamin K
epoxide reductase, which normally reactivates vitamin K, a crucial component in a
number of normal clotting factors, after those factors are consumed in normal
maintenance. Potentially dangerous to all mammals and birds, anticoagulant
rodenticides are a common cause of poisoning in pets and wildlife. Intoxications in
domestic animals have resulted from contamination of feed with anticoagulant
concentrate, malicious use of these chemicals, and feed mixed in equipment used to
prepare rodent bait.
All anticoagulants have the basic coumarin or indanedione
nucleus. The “first-generation” anticoagulants (warfarin, pindone, coumafuryl, coumachlor, isovaleryl
indanedione, and others less frequently used) require multiple feedings to result in
toxicity. The “intermediate” anticoagulants (chlorophacinone and in
particular diphacinone) require fewer feedings
than “first-generation” chemicals, and thus are more toxic to nontarget species. The
“second-generation” anticoagulants (brodifacoum,
difethiolone) are highly toxic to
nontarget species (dogs, cats, livestock, or wildlife) after a single feeding.
Secondary poisoning in nontarget animal species from anticoagulants has also been
documented. The concentration of brodifacoum and bromadiolone in the bait available
as pellets or blocks is usually 0.005% and that of difethiolone 0.0025%.
Anticoagulants antagonize vitamin K, which interferes with the
normal synthesis of coagulation proteins (factors I, II, VII, IX, and X) in the
liver; thus, adequate amounts are not available to convert prothrombin into
thrombin. A latent period, dependent on species, dose, and activity, is required,
during which clotting factors already present are used up. New products have a
longer biologic half-life and therefore prolonged effects (which require prolonged
treatment). For example, the half-life in canine plasma of warfarin is 15 hr,
diphacinone is 5 days, and bromadiolone is 6 days, with maximum effects estimated at
12–15 days. Brodifacoum may continue to be detectable in serum for up to 24 days.
All of these may be detected in liver even after serum levels drop.
Clinical signs generally reflect some manifestation of
hemorrhage, including anemia, hematomas, melena, hemothorax, hyphema, epistaxis,
hemoptysis, and hematuria, any of which may lead to weakness, ataxia, colic,
polypnea, etc. Petechiae rarely develop until after repeated small bleeds have
consumed too many platelets. Depression and anorexia may be seen in all species even
before bleeding occurs. Typically, the onset of clinical signs is delayed (due to
consumption of vitamin K–dependent clotting factors) for 3-7 days after exposure
(can be a little earlier with a fairly large dose). Dogs can also show nonspecific
clinical signs, such as limping or swollen joints (due to hemorrhage in the joints),
coughing or wheezing (bleeding in the lungs), bulging of eyes (retrobulbar
hemorrhages), and pale mucous membrane color. Sudden death with no obvious clinical
signs is also possible.
Anticoagulant rodenticide toxicosis may be diagnosed based on
history of availability of the bait in the animal's environment and evidence of
exposure (missing or chewed up package/bait, passing of greenish blue feces [color
of the bait]) but cannot be discounted if there is no known history of exposure.
Differential diagnoses when hemorrhage is encountered include disseminated
intravascular coagulation, congenital factor deficiencies, von Willebrand disease,
platelet deficiencies, and canine ehrlichiosis. A prolonged prothrombin time (PT),
activated partial thromboplastin time (APTT), or thrombin time in the presence of
normal fibrinogen, fibrin degradation products, and platelet counts is strongly
suggestive of anticoagulant rodenticide toxicosis, as is a positive therapeutic
response to vitamin K1. Stomach contents, serum, or plasma
can be analyzed for the presence of anticoagulant to confirm a diagnosis. Most
veterinary diagnostic laboratories have an “anticoagulant screen” to detect most of
the anticoagulants available in the market in the serum, plasma, liver, or
Vitamin K1 is antidotal. Because the
vast majority of exposures are to the second-generation agents, recommended dosages
are generally 3–5 mg/kg/day, PO, for 3–4 wk. Treating for an extra week will not be
harmful, whereas discontinuing treatment too soon can be lethal. The best way to
know when to stop vitamin K1 treatment is by checking the PT
time 72 hr after the last dose of vitamin K1 has been given.
If PT at that point is normal, treatment with vitamin K1 can
be stopped; if it is still prolonged, treatment with vitamin
K1 for 1 more week is warranted. The doses should be
administered with small amounts of fatty food (milk, meat, or cheese), because fat
will enhance vitamin K1 absorption. Administering half of the
daily dose every 12 hr will provide more constant levels of vitamin
K1. In patients are exhibiting clinical signs when
coagulation factors are abnormal, it is probably safer to avoid injections (unless
the patient is unable to take vitamin K1 orally) because of
the risk of bleeding and hematoma formation at the injection site. Also, the
possibility of anaphylactoid reaction cannot be excluded when vitamin
K1 injection is administered parentally.
Fresh or frozen plasma (9 mL/kg) or whole blood (20 mL/kg) IV
may be indicated to replace needed clotting factors and RBCs immediately if bleeding
is present. Administration of oxygen may be very useful. Activity should be limited
as much as possible during the first week of therapy to minimize bleeds due to
trauma to tissues. Oral vitamin K1 alone (3–5 mg/kg, PO) can
be used to prevent coagulopathy after a known exposure to an anticoagulant.
If a coagulopathy has developed, rechecking the PT and APTT
every 24 hr until normalized should be considered. At the end of a course of vitamin
K1 supplementation, a coagulation profile is needed
~48–72 hr after the last dose to confirm that no indication of coagulopathy
Vitamin K3 given as a feed supplement
is ineffective in treatment of anticoagulant rodenticide toxicosis. Administration
of vitamin K3 by injection in horses has been associated with
acute renal failure and is never an appropriate treatment.
To increase protection to nontarget animal species and children, the US EPA
has promulgated new rules on packaging and availability of anticoagulants. Some
of the highlights of these new rules include the following: 1) Consumer
products available in retail, hardware, grocery, or convenient stores with under a
pound of bait can no longer contain second-generation anticoagulants (brodifacoum,
difethialone, bromadiolone, or difenacoum). 2) Only first-generation anticoagulants
(warfarin, diphacinone, chlorophacinone) or rodenticides other than anticoagulants
(bromethalin, cholecalciferol) are allowed for sale in retail stores for use by
consumers. 3) All outdoor, above-ground use must be in a bait station intended to be
resistant to children and pets. 4) Loose poison baits (pellets, meals) are
prohibited. 5) All outdoor products are to be placed within 50 feet of a building.
6) Professional use products are available in quantities of at least 8 or 16 pounds
(second-generation anticoagulants) or at least 4 pounds (first-generation
anticoagulants); they are to be placed in bait stations. 7) Professional class
anticoagulants (second-generation) are not to be marketed in “consumer” stores
(grocery, hardware, or club stores).
The possible unintended end result of these new EPA
regulations is likely to be a higher incidence of exposure to rodent baits that
contain either bromethalin or cholecalciferol (vitamin D3).
Last full review/revision October 2014 by Safdar A. Khan, DVM, MS, PhD, DABVT; Mary M. Schell, DVM, DABVT, DABT