Siberian Husky ingesting 5-fluorouracil, a human cancer ointment
The review article this month is a case report involving a Siberian Husky ingesting 5-fluorouracil, an ointment applied to the skin for several forms of cancer in human beings. This case report is unique in that it provides sequential blood work from day 1 through day 25 and cytologic examination of the bone marrow on days 8 and 15. It is also the first case report to confirm the presence of echinocytosis in a dog exposed to 5-fluorouracil.
Fry MM, Forman MA: 5-Fluorouracil toxicity with severe bone marrow suppression in a dog. Vet Human Toxicol 48(4):278-180, 2004.
A 19.2 kg spayed Siberian Husky was initially evaluated by a veterinarian for gagging, vomiting, and severe neurological problems. Approximately 12-24 hours before admission, the dog had eaten 1 /4 tube of 5% 5-fluorouracil (5FU) cream for an estimated dose of 32 mg/kg BW. The dog was treated with diazepam, pentobarbital, cimetidine, metoclopramide, ampicillin, IV fluids, metronidazole and enrofloxacin.
Laboratory work on admission (day 1) showed a mild leukopenia, mild thrombocytopenia, mild hyperglycemia and decreased amylase. Laboratory work on days 2-7 showed a progressive, severe neutropenia and thrombocytopenia. Other laboratory abnormalities included electrolyte changes, metabolic acidosis, and mild changes in glucose and enzyme activities.
On day 3 the dog was recovered from pentobarbital anesthesia and developed persistent, non-responsive vomiting. The dog was transferred to a university teaching hospital for further care on day 7 post exposure. At admission to the teaching hospital, the dog was depressed, dehydrated, vomiting, and regurgitating. Electrolyte abnormalities and metabolic acidosis were present, as well as marked neutropenia and thrombocytopenia, monocytopenia, and moderate lymphopenia. Echinocytes were present on the blood smear. The dog was placed on total parenteral nutrition (TPN) and treated with IV fluids, electrolytes, sodium bicarbonate, metoclopramide, enrofloxacin, and ranitidine.
A bone marrow aspirate taken on day 8 showed only stromal elements with no precursor cells present at all. These findings were consistent with marrow aplasia. Filgrastim (Neupogen ® - Amgen Laboratories) was begun on day 9 and continued for 5 days.
By day 9 the CBC showed persistent neutropenia, worsening of marked thrombocytopenia, non-regenerative anemia and pancytopenia. The dog hemorrhaged on day 10 and was treated with 1 unit of fresh, whole blood. This controlled the bleeding and dog was removed from TPN and IV fluids over 48 hours and successfully introduced to solid food. Pancytopenia continued through day 13 and anemia and thrombocytopenia through day 18. A second bone marrow aspirate performed on day 15 showed recovery of hematopoesis. The dog was discharged to home on day 15 with complete resolution of blood abnormalities by day 25.
5-FU toxicity in dogs is well reported and many dogs do not survive. The minimum reported toxic dose is 8.6 mg/kg and the minimal reported lethal dose is 20 mg/kg, with no dogs surviving a dose of 43 mg/kg. Vomiting, tremors and neurological signs, as well as cytopenia are common signs.
Sequential blood work in this dog showed severe leucopenia and thrombocytopenia by day 7 which became even worse by day 9. Pancytopenia continued through day 13 and anemia and thrombocytopenia through day 18. By day 25, all cell lines had returned to normal. The authors postulate that the lag in neutropenia was secondary to depletion of the granulocyte storage pool and the delay in thrombocytopenia dependent on platelet lifespan. Anemia more than likely occurred from hemorrhage as well as impaired production. It is also possible that increased RBC turnover from echinocytosis played an important role in the development of anemia.
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