A nine-year-old neutered male, 5.5kg Bichon Frise presented for evaluation with an initial complaint of decreased appetite, lethargy and potential oral hemorrhage noted after grooming. The dog had no significant medical history reported, was not currently on any medications and was current on vaccines. No dietary indiscretion was initially reported. Physical examination revealed normal vital signs (temperature 101.8 F, heart rate 120 bpm, respiratory rate 20 bpm, and blood pressure 144/68 with MAP 93). He had no abnormalities found on oral examination. He was noted to be slightly tense on abdominal palpation. Thoracic auscultation was unremarkable. He was assessed to be 5-6% dehydrated based on mucous membranes and skin turgor.
Due to the relatively non-specific findings on physical examination, initial diagnostic recommendations included a metabolic evaluation (CBC/chemistry/urinalysis) and abdominal imaging (radiographs). Lab work revealed anemia (PCV 23/TS 5.2), a normal WBC and platelet count, a normal chemistry profile and moderate hematuria. The abdominal radiographs revealed a urinary bladder calculus, left coxofemoral subluxation with moderate secondary degenerative joint disease and an incidental finding of a small quantity of bilateral pleural effusion on the cranial aspect of the films. Thoracic radiographs were subsequently obtained which confirmed pleural effusion and also revealed a severe leftward shift of the cardiac silhouette (suspicious for recumbency related atelectasis) with adjacent alveolar infiltrate involving the left lung. The cardiac silhouette and pulmonary vessels did not appear enlarged and the right lung field appeared normal.
Pleural fluid sampling was considered as the next diagnostic test, but due to the concurrent anemia and history of possible oral hemorrhage, coagulation times were obtained. Both PT and PTT were found to be elevated (PT = 62 seconds with reference range 9-12, PTT 131 seconds with reference range 59-87). Upon further questioning, owner recalled that the dog had potential Decon rodenticide exposure approximately seven days prior to presentation. Therapy for anticoagulant rodenticide toxicity was recommended, including hospitalization, plasma transfusion, oxygen support if needed and vitamin K therapy.
The dog was blood typed DEA 1.1 positive. He was initially placed in oxygen due to hypoxia (SpO2 88% on room air, 94% in 40% oxygen). He was administered ~18mL/kg fresh frozen plasma over 3-4 hours, and subsequently started on Norm-R at 25mL/hr for rehydration. He was administered vitamin K 5mg/kg SQ once, then continued on oral vitamin K at a dose of 2.27mg/kg (12.5mg) PO BID with a fatty meal.
Over the course of the first night of hospitalization, the dog was weaned off oxygen and SpO2 remained 95% on room air. Coagulation times were rechecked and had significantly improved (PT 14, PTT 82). He was noted to have significant ongoing hematuria, and PCV/TS dropped to 18/5.5 necessitating a transfusion with packed red blood cells (pRBC), which resulted in PCV/TS improvement to 27/5.7.
On day two of hospitalization, he began to eat well. Recheck PT had normalized (12 seconds) and PCV/TS remained stable (30/6.5). Repeat thoracic radiographs were obtained in the evening and revealed a persistent small quantity of bilateral pleural effusion and partial resolution of the leftward shift of the cardiac silhouette with mild alveolar infiltrate still remaining.
The dog was discharged to the owners on day three, with instructions to continue oral vitamin K therapy 12.5mg PO BID for four weeks, enforce exercise restriction during treatment, recheck coagulation times 48-72 hours after completing treatment, and to prevent any further access to rodenticide.
Coagulation factors 2, 7, 9, and 10 are produced in the liver in an inactive form. The final step in activation requires vitamin K hydroquinone as an essential cofactor. This carboxylation step converts vitamin K hydroquinone to the inactive form vitamin K epoxide, which is then converted back to the hydroquinone form by an enzyme system (vitamin K epoxide reductase). The anticoagulant rodenticides inhibit this enzyme system, and thus prevent activation of the clotting factors. Once the circulating factors are depleted, the animal can hemorrhage spontaneously or after minor trauma. The delay between ingestion and clinical signs is typically about 48-72 hours due to the time it takes to deplete the circulating active factors. Factor 7 has the shortest half-life (~6.2 hours), and therefore the PT will be prolonged before the PTT. The PIVKA test (proteins induced by vitamin K antagonism) has previously been thought to be a more specific test for diagnosing anticoagulant rodenticide intoxication, but it can be elevated with other disease processes including severe hepatic disease and malabsorption or maldigestion syndromes, and therefore does not provide any clinically useful additional information.
If a patient presents for a known recent ingestion of an anticoagulant rodenticide, treatment recommendations include decontamination (emesis induction, activated charcoal) +/- empiric treatment with vitamin K. First generation anticoagulant rodenticides (warfarin, coumarin) are generally only toxic after repeated exposures, and the coagulation system is affected for approximately one week. The majority of toxicities are due to exposure to second generation products (brodifacoum, bromadiolone), and the effects last for three to four weeks. A recent publication (GE Pachtinger et al, JVECCS 2008) suggests that with recent exposure (within six hours), decontamination and serial assessment of coagulation parameters starting 48 hours post-exposure is a safe and acceptable alternative to empiric treatment with vitamin K. As other commercially available rodenticide products (cholecalciferol, bromethalin, zinc phosphide, strychnine) have very different mechanisms of toxicity, it is critically important to verify the type of poison prior to making treatment recommendations.
With anticoagulant rodenticide toxicity, hemorrhage can occur in a variety of locations and most typically as body cavity effusions or pulmonary parenchymal bleeding. Patients can show a myriad of different clinical signs, including both nonspecific (anorexia, lethargy, weakness) and specific manifestations (cough, dyspnea, hemoptysis, lameness, hematuria, bruising, exophthalmus, pharyngeal swelling, CNS signs, epistaxis, melena). Patients may present with signs of shock if the blood loss has resulted in a significant decrease in circulating volume. Other differential considerations for acute coagulopathy including DIC, severe thrombocytopenia, congenital coagulopathy and hepatic failure should be excluded based on history and other diagnostic tests. Initial therapy consists of both supportive care (volume replacement, oxygen supplementation, pRBC transfusion to improve oxygen carrying capacity, thoracocentesis or pericardiocentesis if indicated) and specific treatment (replacement of deficient clotting factors and initiation of vitamin K therapy). Volume replacement with crystalloids and colloids should be relatively conservative to avoid potential dilutional coagulopathy. As it takes 12-36 hours for regeneration of depleted coagulation factors after initiation of vitamin K therapy, transfusion support is required in patients that are clinically affected. The deficient coagulation factors can be found in frozen plasma, fresh frozen plasma, or fresh whole blood. Suggested transfusion volumes are 10-20mL/kg plasma or 20mL/kg FWB. Autotransfusion of blood that has been removed from a body cavity can be used to replace RBCs, but should not be relied upon to replace coagulation factors. Coagulation times should be reassessed post-transfusion to ensure that the patient is no longer at risk for hemorrhage. Vitamin K therapy should be instituted with an initial dose of 5mg/kg SQ, then continued at 3-5mg/kg/day orally (once daily or divided BID) with a fatty meal to enhance absorption. Intravenous or intramuscular administration of vitamin K is not recommended due to the relatively high risk of complications (anaphylaxis, hematoma formation). Treatment should be continued for at least three to four weeks in the event of ingestion of a second generation rodenticide and coagulation times rechecked 48-72 hours after therapy is completed to ensure that the coagulopathy has resolved. Owners should be counseled to ensure that no further exposure to rodenticide is possible and should also be alerted to the possibility that other pets in the environment could be affected. Anticoagulant rodenticide toxicity is typically associated with a good prognosis assuming that the diagnosis is obtained and aggressive treatment initiated in a timely fashion. It also carries the best prognosis of all causes of coagulopathy, and this diagnosis should be considered in any animal presenting with acute non-traumatic hemorrhage.