Case Report: Malamute with Thrombocytopenia

Honorable Mention, Cases/Abstracts
Hailey Harroun, Colorado

Signalment

Kaiyuh
3yr old FS Malamute
120lb
Longmont, CO

Kaiyuh, a 3-year-old female spayed Malmute, presented to her primary care veterinarian for acute onset epistaxis and a two day history of anorexia. Kaiyuh was current on flea, tick and heartworm medicines, and vaccinations. Owners reported no flea or tick problems and were confident that their pets had no access to rodent poison.  Kaiyuh’s only travel history was to Wyoming, and her only current medication was phenylpropanolamine for congenital urinary incontinence. Kaiyuh appeared bright and alert upon presentation. Initial differentials for Kaiyuh’s signalment were trauma, foreign body, anticoagulant rodenticide toxicity, neoplasia and fungal granuloma.

Diagnostics

The primary care veterinarian examined a blood smear of Kaiyuh’s epistaxis and radiographed her skull. No apparent abnormalities were found on blood smear, and no trauma, tumor or foreign body was found on the radiographs. The primary care veterinarian was concerned about anticoagulant rodenticide poisoning, and recommended that the owners take Kaiyuh to a nearby emergency hospital in order to evaluate her clotting times. She also sent the owners with an injection of Vitamin K for treatment of the presumptive diagnosis. The owners took Kaiyuh to the emergency hospital, at which point the emergency veterinarians noticed hyphema and large patches of echymotic hemorrhage on her abdomen. In-house testing revealed that all clotting times were normal and that Kaiyuh had profound thrombocytopenia with a platelet count of 29,000. PCV was 49, and serum chemistry values were all normal except for an elevated lipase. Top differentials at this stage of the clinical evaluation were infectious thrombocytopenia (Rickettsia, Ehrlichia, Anaplasma), immune-mediated thrombocytopenia and vaccine-associated thrombocytopenia.

Treatment

Owners declined bloodwork to check for tick-borne disease; they also declined an abdominal radiographs and ultrasound to look for internal bleeding. Kaiyuh was placed on IV fluids for volume resuscitation and rehydration, dexamethasone to treat presumed immune disease, doxycycline to treat presumed infectious disease, cyclosporine for immune suppression, and cerenia for nausea suppression. Kaiyuh was monitored in-hospital overnight. The next morning, the epistaxis seemed to have slowed, and Kaiyuh was eating. A re-check CBC showed a PCV of 36, fluids were discontinued, and Kaiyuh was switched to oral prednisone. At noon the next day, the PCV was 33. At 6pm the platelet count was re-checked, and showed no improvement. Vincristine, and anti-neoplastic drug that increases the circulating platelet count, was added to the drug regimen. Kaiyuh remained in the hospital for one more night, with serial monitoring of PCV and platelets. Upon discharge, the platelet count was still less than 30,000; Kaiyuh was QAR and eating normally. Kaiyuh was sent home on her battery of drugs and her owners were given strict instructions to recheck blood work the following week. At this point, the working diagnosis was idiopathic (immune-mediated) thrombocytopenia.

Prognosis

The prognosis for patients with IMTP is initially guarded, with fatal bleeding into the brain or spinal cord possible. Response often takes 3-10 days. Once the platelet count normalizes, the prognosis is fair to good. Many pets may be completely tapered from immunosuppressive medications, although relapse remains possible.

Follow-up

Kaiyuh returned for her check-up one week later. Her owners reported vague lethargy, panting, appetite loss and abdominal distension. No further frank blood leakage had been seen. Current drug regimen at the time of recheck was prednisone, cyclosporine, omeprazole, famotidine, cerenia, doxycycline and phenylpropanolamine. Blood work showed a PCV of 40 and normal platelet count of 387,000. Physical exam revealed cranial organomegaly. A plan was made to gradually switch Kaiyuh from cyclosporine to mycophenolate and to perform a re-check CBC in two weeks.

Patient Outcome

Two days after her re-check appointment at the emergency hospital, Kaiyuh began acting severely weak and lethargic. A follow-up serum chemistry profile was performed by the primary care veterinarian, which indicated that Kaiyuh’s liver enzymes were significantly elevated. The primary care veterinarian communicated to the owners that this was indicative of acute liver failure. At this point, Kaiyuh’s owners elected euthanasia.

Case Review & Discussion

Other potential causes of thrombocytopenia include neoplasia (lymphoma, hemangiosarcoma, leukemia, malignant histiocytosis); infection (Ehrlichia, Rickettsia, Anaplasma); drug reaction (trimethoprim sulfa, phenobarbitol, primidone); hepatic disease; pancreatitis.

 Other diagnostics that could have been considered was a bone marrow aspirate to rule out neoplasia, and an assay for platelet-bound antibody. The assay is highly sensitive but not specific for a IMTP. A diagnosis of IMTP is unlikely if the test is negative. With treatment including both prednisone and vincristine, the platelet count is expected to rise to more than 50,000 per uL within 7 days of treatment. Thrombosis has been rarely seen in patients after rapid rise of the platelet count.

 Patients with rapid (<3-5 days) rise of their platelet count to >200,000/ μL. may have their immunosuppressant medications tapered more quickly and/or antithrombotic medication administered. Kaiyuh’s platelet count increased to >300,000/uL by one week after initiation of treatment. There are several unexplained findings in this case. One of these discrepancies is the rapid increase in the leukocyte count between Dec. 11 and Dec. 12. The high end of normal leukocyte count in dogs is 17,000/uL, and Kaiyuh’s leukocyte count was 33,000/uL on Dec. 12 and 30,000/uL on Dec. 14. This finding is unexpected because administration of Vincristine (on Dec .12) is a myelosuppressive agent which decreases the leukocyte count, especially neutrophils. In this situation, leukopenia is expected, not leukocytosis. By the time of the re-check on Dec. 19, the leukocyte count had again normalized to 9.5K.

 Another discrepancy in the case is the presumptive diagnosis of acute liver failure. The diagnosis of liver failure was made based on elevated liver enzymes. Two of Kaiyuh’s medications - prednisone and doxycycline – are documented to cause elevated liver enzymes. Potential causes of acute liver failure include idiosyncratic drug reaction, aflatoxin in contaminated dog food, xylitol toxicity, organochloride pesticides, Leptospirosis, Ehrlichia, acute pancreatitis. Alfatoxin toxicity is unlikely because other dogs in the household were not affected. The toxicities are unlikely based on owner history. Leptospirosis would have presented with a fever and concurrent renal failure. Acute pancreatitis is expected to present with vomiting, diarrhea and fever. Idiosyncratic hepatic injury has been reported with doxycycline administration.