Interpreting blood profiles in non-domestic small mammals

Vet Times The website for the veterinary profession https://www.vettimes.co.uk Interpreting blood profiles in non-domestic small mammals Author : Vicki Baldrey, Ian Ashpole Categories : Exotics, Vets Date : December 10, 2012 Vicki Baldrey and Ian Ashpole conclude their article on the blood profiles of exotics, by advising on interpreting the results of blood samples taken from small mammals. Table 1. Reference ranges for haematological parameters in selected small mammal species. This article, the final in a series of four, focuses on the interpretation of haematology and biochemistry results from some of the small mammals that are increasingly encountered as patients in general practice. Earlier parts appeared in VT42.39, VT42.42 and VT42.45. Most small mammals are considered to be prey animals naturally and, like some reptile and avian species, they are often adept at disguising clinical signs of disease until pathology is advanced. It is, therefore, important the veterinary surgeon is able to perform a logical investigation of the 1 / 9

patient s problem, including blood sampling where relevant, to facilitate rapid, appropriate treatment. Please refer back to the first article in this series on obtaining a sample (VT42.39), for guidance regarding the collection of blood samples from small mammals. The other features appeared in VT42.42 and VT42.45. Reference ranges Table 2. Reference ranges for biochemical parameters in selected small mammal species. The laboratory will often provide a set of reference ranges based on its own results; however, for less commonly encountered species this data may be limited. Care should, therefore, be taken to evaluate the source of the ranges prior to their application. Tables 1 and 2 present general reference ranges for the more commonly encountered species. Haematology 2 / 9

Unlike birds and reptiles, small mammal red cells are anucleate and so haematology may be run on an automated machine. However, if only a small sample is obtained, a manual packed cell volume (PCV) and blood smear examination can be very informative. Regardless of method, some parameters, such as platelet numbers, should be confirmed by examination of a blood smear, as small clots in the blood sample or clumping of platelets may artificially lower the count. When interpreting haematology, attention should be paid to the method of sampling, as some parameters may be affected by general anaesthesia. This is most commonly documented in ferrets, where parameters including the PCV and white blood cell count have been shown to decrease by 20 per cent to 30 per cent under isoflurane anaesthesia, due to sequestration of cells into the spleen. Red cell changes can generally be interpreted in a similar way to those for cats and dogs; it should be noted, however, the erythrocyte lifespan is shorter in many small mammal species and, therefore, anaemia may develop at an earlier stage of disease. A mild, non-regenerative anaemia is often one of the first indications of disease and should be monitored closely, while the underlying cause is investigated. Figure 1. Bone marrow biopsy from the proximal tibia of a ferret. Non-regenerative anaemia may be associated with chronic renal insufficiency, chronic infectious or inflammatory disease, neoplasia, malnutrition and bone marrow disorders. Bone marrow biopsy may be indicated to investigate further if an underlying cause cannot be determined (Figure 1). Pancytopaenia may be encountered in entire female ferrets due to bone marrow suppression, as a result of hyperoestrogenism during prolonged oestrus. The same blood picture may be seen in a neutered jill with an active ovarian remnant. Sometimes these patients present collapsed with such pale mucous membranes that stabilisation and/or blood transfusion are required before attempting blood sampling. It is less common to see changes to the haematology with adrenal disease in ferrets. However, non- 3 / 9

regenerative anaemia and even pancytopaenia may occur in very advanced cases. It is important to note that adrenal gland disease in ferrets is very different to Cushing s disease seen in dogs, with no change to serum cortisol concentration in affected ferrets. Serum androgens are elevated in ferret adrenal disease and these may be measured to confirm the diagnosis. An increase in one or more of the hormones oestradiol, 17-hydroxyprogesterone or androstenedione is considered highly suspicious. Regenerative anaemia occurs secondary to blood loss, toxicosis and immune-mediated destruction (rare). Blood loss anaemia is common in entire female rabbits as a result of haemorrhage associated with uterine adenocarcinoma. Gastrointestinal bleeding due to ulceration is also very common, often seen secondary to stress or underlying disease, particularly in rabbits and ferrets. Thrombocytopaenia may be associated with infection, haemorrhage, toxin exposure and neoplasia. Elevated platelet counts may occasionally be observed with severe inflammation or sepsis. Rabbits are sometimes described as having heterophils, instead of neutrophils, but the latter term will be used in this article. In rabbits, and some rodent species, the total white cell count does not usually increase in the face of infection, rather the ratio of neutrophils to lymphocytes changes. In a healthy individual, the ratio is approximately 1: 1; however, in response to infection, an increase in neutrophils is seen, with a relative decrease in the lymphocyte count. This may be accompanied by toxic changes to the cells, as noted on examination of a blood film. A relative lymphopaenia is a common, non-specific reaction to chronic disease in rabbits. An interesting feature of guinea pig haematology is the occurrence of Kurloff cells, a type of lymphocyte containing cytoplasmic inclusion bodies (so-called Kurloff bodies ), thought to be produced in response to oestrogen stimulation. This cell is seen most commonly in breeding female guinea pigs (although they may be observed in juvenile and male animals) and is thought to have a cytotoxic effect on leukaemic cells. A further peculiarity of guinea pig haematology is the absence of a stress leucogram, which may be seen with other small mammal species, as a result of transport and/or handling. Ferrets show white cell changes similar to those of dogs and cats with a leucocytosis seen in response to infection and inflammation, often with a left shift and toxic changes seen on morphological examination of neutrophils. An absolute or relative lymphocytosis is often associated with lymphoma, although lymphoma can be present in the absence of haematological change. Examination of a blood film may show unusual lymphocytes with mitotic figures and blast cells. Further tests, such as histopathology of a lymph node biopsy, are usually required to confirm this diagnosis. Biochemistry 4 / 9

Proteins Serum protein levels may increase with dehydration and immune stimulation and may decrease with starvation, liver disease and protein-losing enteropathy or nephropathy. Albumin in rabbits shows diurnal fluctuations and so may be more difficult to interpret in this species. An increased globulin concentration due to hypergammaglobulinaemia may be seen in ferrets with Aleutian disease, although this is an inconsistent finding. Calcium and phosphorus Disorders of calcium and phosphorus are generally similar to other mammals, but rabbits are different, having a much higher blood calcium level than other mammals as they do not rely on vitamin D for gastrointestinal absorption. Rather, calcium is passively absorbed across the intestinal mucosa, with the majority of excess calcium excreted via the kidneys: this explains the sludgy urine often encountered in these animals. Dietary phosphorous is important in herbivores as excess intake leading to high blood concentrations can affect bone calcification, and may lead to metastatic calcification of tissues. Renal parameters Figure 2. Lateral abdominal radiograph of a guinea pig demonstrating renal and cystic calculi. Azotaemia in small mammals is consistent with renal failure and, as with other mammals, may be prerenal, renal or postrenal in origin. 5 / 9

Prerenal causes of azotaemia include dehydration, gastrointestinal bleeding or recent ingestion of a high protein meal. Postrenal azotaemia may occur secondary to urolithiasis, seen commonly in guinea pigs (Figure 2) or, potentially, due to prostatic enlargement associated with adrenal disease in male ferrets. Encephalitozoon cuniculi infection is an important differential diagnosis for azotaemia in rabbits, although infection with this protozoal parasite may also manifest as a neurological syndrome or as ocular disease (Figure 3), with or without concurrent azotaemia. Serology is available as a screening tool, although results may be difficult to interpret. The availability of a test for IgM antibodies may be useful in conjunction with an IgG titre to help differentiate active infection from previous exposure. Figure 3. Anterior uveitis in a rabbit secondary to Encephalitozoon cuniculi infection. The normal creatinine concentration range in ferrets is lower than that of other mammals. Due to the mechanisms of excretion of creatinine in ferrets, elevations are not always seen in association with the uraemia seen in acute renal failure. Any elevation to creatinine, however, is considered to be significant and if found in association with elevated phosphorus concentration is suggestive of severe, chronic renal disease. Reduced urea in herbivores, such as the rabbit, is often associated with decreased food intake or lack of caecotroph ingestion (usually secondary to obesity, dental disease or lumbosacral disease), while reduced urea in carnivores, such as the ferret, may reflect reduced food intake or severe liver disease. Liver parameters 6 / 9

The diagnosis of liver disease can be complicated in small mammals, as with other species. Blood results must often be interpreted alongside diagnostic imaging results and in some cases histopathology of a liver biopsy may be required to make a definitive diagnosis. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are markers of hepatocellular damage; however, as in dogs and cats, they often lack specificity. ALT has been shown to be of value in assessing hepatic damage in ferrets, but is less useful in rabbits, guinea pigs and chinchillas, as the enzyme has lower activity in herbivores. Elevation to alkaline phosphatase (ALP) may be seen in conditions causing biliary stasis; however, this enzyme is also non-specific, being found in many other tissues including bone, intestine and kidney. Bilirubin will increase in response to both hepatocellular damage and biliary stasis, so may also be useful in the diagnosis of liver disease. Bile acid assay remains the best indicator of hepatic function, although reference ranges are not readily available for some species. Hyperadrenocorticism has been documented in guinea pigs, gerbils and hamsters and may be characterised by elevated ALP and cortisol levels alongside clinical signs of symmetrical alopecia, polyuria and polydipsia. Hepatic lipidosis is commonly encountered secondary to anorexia in small mammals and is especially common in rabbits. It is often difficult to definitively diagnose as it is accompanied by inconsistent changes to the animal s biochemistry, although elevated ALP and hypercholesterolaemia may be present in some cases. Reliance may have to be made on a suspicious history and clinical signs, with a liver biopsy required for definitive diagnosis. Glucose Hyperglycaemia is usually associated with stress in small mammals and it has also been associated with active bacterial infection. Diabetes mellitus is considered very rare, but it has been documented in guinea pigs, chinchillas, gerbils and degus, characterised by persistently elevated blood glucose concentration and in some cases elevated cholesterol, especially if associated with obesity. Significant hyperglycaemia may be seen in rabbits secondary to stress, but it has also been documented in association with severe pain due to intestinal obstruction and terminal hepatic lipidosis. Evaluating blood glucose may therefore be helpful in differentiating gut stasis from intestinal obstruction, with values above 20mmol/l indicating a poor prognosis and, probably, a surgical condition. Hypoglycaemia is uncommon in rabbits and rodents and, if observed, usually reflects reduced food intake or starvation. It may also occur with sepsis. Severe, persistent hypoglycaemia in ferrets is consistent with excessive insulin production due to insulinoma. 7 / 9

Ferrets with insulinoma can usually maintain a normal blood glucose concentration when fed frequently, so a period of fasting may be required for diagnosis. This should not exceed four to six hours and the ferret must be monitored closely for signs of hypoglycaemia. Conclusion Interpretation of blood profiles in non-domesticated animals is complicated by significant differences in physiology and response to disease between species. Attention must always be paid to the entire clinical picture when making a diagnosis, not just the individual blood results. Acknowledgment The authors would like to thank Michael Orsi for providing a photograph. References Antinoff N (2007). Small mammal and rabbit clinical pathology, Western Veterinary Conference, Las Vegas, Nevada. Harcourt-Brown F (2002). Clinical pathology. In Textbook of Rabbit Medicine, Reed Elsevier. Harcourt-Brown F M and Harcourt-Brown S (2012). Clinical value of blood glucose measurement in pet rabbits, Veterinary Record 170(26): 674. Hernandez-Divers S (2005). Rabbits. In Carpenter J (ed) Exotic Animal Formulary (3rd edn), Elsevier Saunders. Jenkins J (2000). Rabbit and ferret liver and gastrointestinal testing. In Fudge A (ed) Laboratory Medicine: Avian and Exotic Pets, W B Saunders. Jenkins J (2006). Clinical pathology. In Meredith A and Flecknell P (eds), BSAVA Manual of Rabbit Medicine and Surgery (2nd edn), British Small Animal Veterinary Association. Jenkins J (2008). Rabbit diagnostic testing, Journal of Exotic Pet Medicine 17(1) 4-15. Lennox A (2009). Ferrets: clinical pathology. In Keeble E and Meredith A (eds), BSAVA Manual of Rodents and Ferrets, British Small Animal Veterinary Association. Marini R P, Callahan R J, Jackson L R, Jyawook S, Esteves M I, Fox J G, Wilkinson R A and Strauss H W (1997). Distribution of technetium 99m-labeled red blood cells during isoflurane anesthesia in ferret, American Journal of Veterinary Research 58(7): 781-785. Ness R (2005). Rodents. In Carpenter J (ed) Exotic Animal Formulary (3rd edn), Elsevier Saunders. Rosenthal K (2010). Ferrets and rabbits: clinical pathology, Western Veterinary Conference, Las Vegas, Nevada. Wesche P (2009). Rodents: clinical pathology. In Keeble E and Meredith A (eds), BSAVA Manual of Rodents and Ferrets, British Small Animal Veterinary Association. 8 / 9

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