Anticoagulant rodenticide toxicity represents that rare gem in realm of canine toxicities: a toxin for which there is both a rapid, bedside diagnostic test and an antidote. Even severely affected clinical cases stand a reasonable to good chance of recovery with the assistance of transfusion products - and here is an occasion when transfusion products are part of a curative therapy rather a temporary band aid (as can be the feeling when they are utilized in therapy for more insidious forms of anemia). Furthermore, if thoroughly questioned, most owners are aware of a potential exposure. While it may seem a bit perverse, it is for these reasons that anticoagulant rodenticides are among the “favorite” toxicities of many an ER vet.
So, what’s not to love? Why am I writing (again) about what is ostensibly such a well-known toxicity? Simply put, it’s because pets are still suffering from or dying from exposure to these pest removal products. Shockingly, many pet owners remain unaware of the danger: I have met more than one dog owner within the past year who was well-versed on the risks of chocolate ingestion but did not realize that the blue pellets in the basement could be far more deadly. In addition, recognizing hemorrhage due to coagulopathy and the possible role of a rodenticide as the underlying cause is not always straightforward. The sneaky trick of a delay of about a week between exposure and active hemorrhage seems to be the most likely reason this differential diagnosis slips under the radar. Finally, therapeutic decisions regarding the hemorrhaging patient can be quite stressful – such as when to transfuse and deciding whether and when to perform thoracocentesis on a coagulopathic patient with hemothorax.
Earlier in the year, I felt compelled to revisit this subject matter after what felt like a string of coagulopathic patients arrived both on referral and first presentation. In more than one case, progression to catastrophic bleeding may have been avoided by earlier diagnosis; which could have been achieved by phrasing questions about exposure history to include several days to a week prior to presentation. This his hit even closer to home last month, when my own sister’s dog spent 2 days (and her family’s spring break budget) in the ICU in Wisconsin. Our whole family just feels lucky that she survived.
For me, working on my own ICU 2000 miles away, it all started with a text: “Roxy is sick L.” Upon questioning, my sister texted that Roxy was lethargic and not eating or drinking. She was seen presented to her veterinarian that morning, but physical exam seemed unremarkable. She seemed much better while at the vet but was very lethargic again once home. Diagnostics were planned for the next day should she fail to show improvement. My sister had explained to her veterinarian that Roxy – young, recently adopted and quite a handful - managed to bolt out through the front door and run off the night before. She was missing for one hour, and certainly may have experienced trauma or ingested something untoward during that time.
By three AM the following morning, Roxy was breathing abnormally and my sister was increasingly concerned. She was unable to wait for her vet to re-open, and rushed Roxy to the emergency veterinary hospital nearby. On examination in the ER, she now had pale gums and a rapid heart rate. Pleural effusion was detected on T-FAST scan. PT and PTT were both too high to read. With her clinical signs now so declared, my sister was asked whether Roxy had any potential access or exposure to rat bait. With chagrin, she admitted that about a week prior Roxy had gained access to portion of the basement normally closed off to her and where my sister suspected (and later confirmed) there might be some D-Con. Roxy’s situation was critical. She received a plasma transfusion, thoracocentesis, and then additional blood transfusion due to the severity of her anemia. She made it home, completed 30 days of Vitamin K therapy, and is up to her old antics again. Recently her recheck PT/PTT off Vitamin K showed she is in the clear.
In Roxy’s case, the fact that she had gotten out of the house and was unsupervised for a time the night before her initial clinical signs created a giant red herring that may have played a role in delaying her diagnosis. With the timeline of her case, it seems less likely (though not impossible) that initiation of Vitamin K therapy alone would have prevented the hemorrhage that caused her pleural effusion later that night. Had the PT and PTT been performed the first day, and pre-emptive plasma transfusion administered, the progression to catastrophic bleeding may have been avoided.
Though I don’t really believe her, my sister stated at one point that if she and her husband had known up front that Roxy’s care would cost over $3000, they might not have initiated therapy. The photo of Roxy reunited with my nephews is priceless, but not all families can invest such funds in the care of their pet. Most can afford Vitamin K - so obtaining a detailed history of possible exposures ranging back to a week or two before presentation can be life saving.
There are multiple forms or generation of anticoagulant rodenticide on the market, including brodifacoum, diphacinone, warfarin, bromadiolone, and others. Most of these products include green dyes for a characteristic appearance – owners should be questioned as to whether they have seen any green or blue material in their pet’s feces or vomitus.
The mechanism of action of anticoagulant rodenticides is inhibition of the vitamin K epoxide reductase enzyme necessary for “recycling” of vitamin K in the liver. As vitamin K stores subsequently become depleted, there follows a reduction in functional vitamin K dependent clotting factors necessary for normal coagulation. Vitamin K is necessary for post-translational activation of non-functional forms of coagulation factors II, VII, IX, and X into the functional proteins required for the intrinsic, extrinsic, and common pathways of the clotting cascade.
Clinical signs typically reflect spontaneous bleeding, more often into body cavities such as the abdomen, thorax, or joints. Depression and anorexia may be seen even before bleeding occurs. Any large volume hemorrhage will manifest more externally as weakness, lethargy, and pale gums. Hematomas or hyphema would be more expected than petechiae or ecchymoses, but melena, epistaxis, hemoptysis, or hematuria may be seen. Dogs can also show nonspecific clinical signs, such as limping or swollen joints, coughing, or ocular swelling due to retrobulbar hemorrhage. If pericardial or intracranial hemorrhage occurs, this can lead to sudden death.
A latent period, dependent on species, dose, and activity, is required, during which previously activated clotting factors are used up. It is important to note that clotting times will be elevated prior to the occurrence of active hemorrhage and typically within 48-72 hour of exposure. When vitamin K1 was prohibitively expensive, a common protocol for acute exposure (within roughly 4 hours of exposure) was decontamination via emesis, and provision of activated charcoal with sorbitol. Measurement of baseline PT/PTT is performed, followed by recheck PT/PTT after 72 hours. If still normal, therapy should not be required. This protocol is still quite reasonable, but if there is any doubt as to whether a client will follow up for recheck at the 72 hour mark, it is safer to prescribe vitamin K.
Diagnosis further out from ingestion is made on the basis of history of possible exposure, clinical signs, and prolonged clotting times. Prothrombin time (PT) will be elevated earlier than partial thromboplastin time (PTT) because PT measures the extrinsic pathway and factor VII has the shortest half life of all the vitamin K dependent factors. Differential diagnoses for typical signs upon presentation include hemorrhage secondary to neoplasia, idiopathic pericardial effusion, ITP or other thrombocytopenia, IMHA, or congenital factor deficiencies, but diagnosis is often straightforward based on history and clotting times. Veterinary diagnostic laboratories have an anticoagulant screen to detect most of the anticoagulants available in the market in the serum, plasma, liver, or kidney. However, treatment must be initiated long before such results would be available. Post mortem diagnosis is possible via such tests.
Providing exogenous vitamin K1supplementation for the duration of toxic effects is the antidote for these toxicities – replacing the stores that the liver is unable to “recycle.” Recommended dosage is 5 mg/kg/day by mouth for four weeks (2.5mg/kg q 12hr), fed with a fatty meal to enhance absorption. Later generation products have a longer biologic half-life and therefore prolonged effects requiring prolonged treatment. For example, brodifacoum may continue to be detectable in serum for up to 24 days. Prothrombin time should be rechecked 48-72 hours after last dose administered to ensure the duration of therapy has been adequate – it is better to err on the side of longer duration of therapy. If values are elevated, therapy should be resumed for a further week, once again followed by recheck PT/PTT 48-72 hours following cessation of therapy. Oral dosing is preferable, safer, and more effectively absorbed than injectable vitamin K, but SQ injection may be used for a patient that cannot receive oral medication. Activity should be limited as much as possible during the first week of therapy to minimize bleeds due to trauma to tissues.
Vitamin K3, which may be found in a very inexpensive form, is not an effective therapy and can have toxic effects of its own. It should never be used in place of vitamin K1.
If bleeding is present or profoundly elevated clotting times are detected, fresh or frozen plasma (10 mL/kg) or whole blood (20 mL/kg) transfusion is indicated immediately to replace needed clotting factors +/- red blood cells. PT and PTT should be rechecked every 24 hours until normalized. Some patients require multiple transfusions to stabilize. Units of frozen plasma may be kept on hand for over a year, so purchase of such a unit from the blood bank here at Dove Lewis or elsewhere can certainly be a worthwhile investment.
In my mind, hemothorax due to rodenticide toxicity presents a unique form of pleural space disease, because it is perhaps the one time when the “better out than in” adage is not always in effect. If dyspnea is not severe, I lean toward providing oxygen supplementation and transfusing plasma first in hopes of normalizing clotting times. If the respiratory status is stable, thoracocentesis is not always necessary as the patient may reabsorb a moderate quantity of blood present in the thorax. If dyspnea is severe, thoracentesis must be performed. It is possible to utilize blood obtained from the thorax or abdomen for autotransfusion for packed red cells, though of course there will be no beneficial clotting factors present in such a transfusion. If you have questions about administering a transfusion, you can call DoveLewis at any time.
Please note that there are other rodenticides such as those containing bromethalin, zinc phosphide or Vitamin D, which work by different mechanisms. They will not be addressed in this article, but cannot be effectively treated with Vitamin K. Whenever possible, it is important to have the owner bring any packaging they may have for the product to which their pet was exposed.
While anticoagulant rodenticides pose a serious risk to our veterinary patients, we at least have an antidote to their potentially deadly effects. With vigilance for clinical signs - and prompting owners to think back to exposures that may have occurred several days prior to even subtle signs, severe effects of the toxicity may be avoided with just Vitamin K therapy. The benefit of early plasma transfusion should not be discounted in the coagulopathic patient and carries a relatively low risk even without blood typing or crossmatching. Though the effects of any toxicity on our patients are never desirable, anticoagulant rodenticides will remain a favorite of mine because it is nearly always treatable – we can really help these dogs!