Bruce H. Williams, DVM, DACVP
Chairman, AFIP Department of Telemedicine
Armed Forces Institute of Pathology
Washington, DC 20306-6000
(202) 782-2392
Fax: (202) 782-9010
Email: williamsb@afip.osd.mil
As I have often said before, ferrets are not dogs, nor are they cats. Too many veterinarians attempt to use their knowledge of these two species in order to treat the domestic ferret. Now there are a number of ways that this can get you in trouble, but the most common way is in the interpretation of clinicopathologic data. This text will concentrate on tests that are commonly run on ferrets as well as common errors of interpretation are made.
The reader will note that normal values are not part of this handout. Normal values vary widely from laboratory to laboratory; however, most large commercial labs have compiled sufficient amounts of data in order to provide normal values for ferrets in their laboratory, just like they do for dogs and cats. The first mistake that you can make in interpreting ferret bloodwork is to take your normals out of a textbook!!!. If your lab doesn’t provide normal values, give them a call. While textbook normals can be used in a pinch, realize that your are dealing with generalizations at this point, and don’t interpret slightly elevated values to strictly.
The CBC and chemical profile of the ferret generally requires no more than two milliliters of blood. Practitioners should always try to use the smallest tubes possible, as placing only 0.5 cc of blood in a 3-ml EDTA tub may result in artifactual changes of hematological values. The average blood volume in a female ferret is approximately 40 ml, while that of a large male ferret is approximately 60 ml. Up to 10% of the blood volume can be safely extracted from a healthy ferret; generally this is only required during transfusion.
The Complete Blood Cell Count
CBC’s will yield tremendous amounts of information. Because ferrets often don’t willingly give up their blood, and many practitioners have trouble hitting their veins, a quick sedation with isoflurane is often needed in order to retrieve the sample. While this is acceptable practice, remember that isoflurane will artificially lower most CBC parameters across the board, and this should be factored into your interpretation.
Ferrets normally have a packed cell volume higher than the dog and cat, with normal values in the 45-60% ballpark. Perfectly normal healthy ferrets may have a PCV of 65, and this should not be interpreted as dehydration without other corroborating data, such as elevated total protein levels, and a high urine specific gravity, or clinical signs of dehydration.
White blood cell counts in the ferret are often confusing to vets who are unfamiliar with this species. While there is some variation between fitch and albinos, and males and females, the normal white count of the ferret is low, from 2500 to 7000/cm3. This occasionally leads to an erroneous diagnosis of leukopenia. When considering leukopenia in the ferret, look for elevated numbers of bands neutrophils in the peripheral blood. Values for calculating a left shift in the dog are valid for that in a ferret. Another finding that may support a diagnosis of leukopenia would be a concomitant anemia and/or decrease in platelets, such as might be seen in bone marrow suppression in estrogen toxicosis or the very rare case of adrenal-associated endocrinopathy.
Conversely, leukocytosis should be considered in cases in which WBC counts exceed 9,000. The stress response is not a significant cause of elevated white counts, due to the ferrets’ innate resistance to cortisone. So even marginal elevations of leukocytes over accepted lab normals should be taken into account, and inflammatory disease should be suspected.
A common misconception among practitioners is in the area of evaluation of the differential count. It is not uncommon, especially in older ferrets, to see elevated numbers of lymphocytes, which can often be demonstrated on a series of CBC’s performed at 2-4 week intervals. This has been referred to as "persistent lymphocytosis". In some cases, lymphocyte counts may even exceed neutrophil counts. Several years ago, practitioners circulated the notion that persistent lymphocytosis is evidence of lymphosarcoma in the ferret, and even went so far as to publish this concept. Based on this "fact", it was not uncommon for ferrets to be diagnosed with lymphosarcoma solely on the results of a CBC, and some were even treated with chemotherapeutic agents! Diagnosis of lymphosarcoma in the ferret must be confirmed by biopsy of a peripheral lymph node, visceral organ, or bone marrow aspirate which shows the formation of either solid tissue neoplasms, or in the case of the bone marrow, replacement of the normal marrow by infiltrates of lymphocytes exceeding 20% overall.
As in other species, however, the most common cause of elevated lymphocyte levels is chronic smoldering infection, not neoplasia. Gastric Helicobacter infection is a ubiquitous inflammatory disease of ferrets, and often causes a profound inflammatory response resulting in atrophic gastritis, mesenteric lymphadenopathy, and often splenomegaly. Additionally the large amounts of inflammatory mediators arising regionally often results in a low-grade systemic inflammatory response, and a low to moderate rise in circulating lymphocytes.
Rarely, a practitioner will encounter peripheral eosinophilia in the ferret. The most common cause of eosinophilia in ferrets is a recently described (1991) disease known as eosinophilic gastroenteritis. This is actually a misnomer, as eosinophils may be found in virtually any abdominal organ, including the liver, pancreas, and mesenteric lymph nodes. The cause of eosinophilic is yet unknown, however, due to the marked eosinophilic response in affected organs, both hypersensitivity and parasitism are possible causes for this syndrome. Hypersensitivity conditions and parasitism are uncommonly seen in American ferrets; however, low-grade eosinophilia may be recorded in heartworm infection.
The Chemistry Profile
As with the CBC, there are several unique features of the chemical profile
of the ferret; indeed, it is with the clinical chemistry that the majority
of misdiagnoses are made by the "un-ferret-knowledgeable" practitioner.
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| Liver from an anorexic ferret. Note that this is a physiologic change rather than a pathologic one. (Photo courtesy of Dr. Richard Montali, National Zoological Park). |
In conjunction with this physiologic change, elevations of ALT up to 800 mg/dl can be seen, and alkaline phosphatase up to approximately 100 mg/dl. This often causes confusion to practitioners, who render an erroneous diagnosis of unspecified hepatic disease. However, hepatic disease is quite uncommon in this species; the most common cause of true hepatic disease in the ferret is neoplasia, with lymphosarcoma causing 95% of cases. Rarely bacterial infections of the liver or biliary tree may be seen.
The diagnosis of hepatic disease in the ferret must be based not only on ALT and alkaline phosphatase, but other clinical indicators in the CBC and chem panel. Clinical elevation of icterus or an elevated bilirubin is an excellent indicatior of primary hepatic disease, or concomitant leukocytosis or pyrexia may lend additional credence to a diagnosis of primary hepatic disease.
Decreased total protein and mild hypoalbuminemia is a common finding in both ill and older ferrets. Most commonly, hypoalbuminemia indicates prolonged anorexia in the ferret, but it is also a common feature in long-standing inflammatory disease of the gastrointestinal tract. In older animals, gastroduodenal infection by Helicobacter mustelae is a common cause of mild hypoalbuminemia, and in young animals, any inflammatory bowel disease may cause this sign.
An interesting finding in evaluating the renal enzymes of ferrets is the relatively insensitivity of creatinine as an indicator of renal failure. Kawasaki et al. In 1995 documented a number of cases in which animals with histologic evidence of end-stage kidneys and blood urea nitrogen levels of 300-400 had creatinine levels lower than 3.0 mg/dl. In fact, the normal creatinine of this species averages approximately half the level of the dog and cat. In evaluation of azotemia, the prudent practitioner should also evaluate urine specific gravity on a routine basis, rather than awaiting elevations in creatinine for confirmation of renal disease.
Finally, one of the most commonly aberrant values in the chemical profile
of the older ferret is the blood glucose level. As insulinoma is the most
common neoplasm of the American ferret (interestingly, this is an uncommon
disease in other parts of the world), a recommendation for yearly evaluation
of this parameter after the age of three appears prudent. Ferrets with
levels of insulin less than 80 g/dl should suggest a possibility of insulinoma,,
and levels between 60 and 80 necessitate further testing, to include a
fasting glucose test, and possibly, an amended insulin/glucose ration.
(Absolute insulin concentrations in this species may result in false negative
findings). Ferrets with blood glucose levels less than 60 g/dl, especially
in the presence of clinical signs of lethargy and stupor, should be considered
candidates for surgery as soon as possible after stabilization. In cases
of hypoglycemia, elevated hepatic enzymes may result from inanition and
mobilization of peripheral fat stores. Contrary to published information,
this is not evidence of hepatic metastasis of insulinoma; in fact, metastasis
of islet cell tumors has not been documented in this species. As opposed
to islet cell neoplasia in the dog and cat, islet cell tumors in the ferret
exhibit benign behavior and metastasis is not seen. However, 40% of ferrets
will develop additional neoplasms within 10 months. This however, is not
consistent with the definition of metastatic disease or malignant behavior.
Adrenal Testing
Although not a typical part of the normal bloodwork of the ferret, occasionally the ferret practitioner will be call on to examine the ferret with marginal hair loss, possibly a sign of early adrenal-associated endocrinopathy due to excessive release of estrogen from a proliferative adrenal lesion. (Note - hyperplastic lesions of the adrenals are as likely to cause these clinical signs as neoplastic lesions.) While it is my firm belief that if clinical signs are obvious, such as marked truncal alopecia, vulvar swelling in spayed females, or a return to sexual behavior in male ferrets, then exploratory surgery may be performed without further testing. However, in the case of marginal clinical signs, or nervous owners, specific testing is available.
Because adrenal disease is the result of hyperestrogenism, not hypercortisolism, as in true Cushing's of the dog, the typical testing regimes used in the dog and cat (cortisol, ACTH stimulation test, dexamethasone suppression test) will generally yield little clinical information. CBC’s and chemistry profiles are generally normal. Occasional hypoglycemia is seen in ferrets with adrenal disease, generally as a result of the ferret being in the primary age group for development of these common tumors, rather than any predilection for multiple endocrine neoplasms, as has been theorized.
Specific testing for adrenal disease in the ferret is available through the Department of Endocrinology at the University of Tennessee College of Veterinary Medicine (615-974-5638). A special profile, requiring 1 cc of serum is performed to evaluate levels of estradiol and a number of pre-hormones produced by the adrenal cortex, including androstenedione, dehydroepiandrosterone sulfate, or 17-hydroxyprogesterone, among others. Correct interpretation of this assay is predictive of adrenal disease in 95% of cases. Intact female ferrets and those with functional ovarian remnants (a very uncommon finding, contrary to reported information) may result in elevated levels of estradiol, but not of other intermediates. If estradiol and any of the intermediates are elevated, or any of the intermediates are elevated, a strong suspicion of adrenal disease is incurred, and surgery should proceed.
Bruce H. Williams, DVM, DACVP
January 1999