Nontraditional mammalian species, such as ferrets, lagomorphs, marsupials, hedgehogs, and rodents, are stoic by nature and have evolved to mask their illness to avoid predation. This behavior can create a clinical challenge for the veterinarian and a false sense of security for an owner. In some cases, an animal that appears clinically normal may have a terminal illness. Hematology and plasma biochemistry analysis can be used to evaluate these species to characterize their true physiological status and aid in disease diagnosis.

When working with small species, it is important to determine the volume of blood that can be safely collected from the patient. The blood volume of a mammal is approximately 10% of the animal's body weight. In general, 1% of the total blood volume can be safely collected for sample processing, which is approximately 1.0-ml/100-gr BW. Because of the small size of some of the exotic mammals, veterinarians may be concerned that they cannot collect enough blood to perform a hematologic or chemistry profile; however, most laboratories or analyzers can perform a complete blood count (CBC) and plasma chemistry analysis on 1-ml of blood. It is important to consider the animal's history and physical examination findings when determining the volume of blood that can be safely collected. If an animal has experienced an acute blood loss, than a reduced volume of sample should be collected.

Blood samples should be placed into appropriate collection tubes immediately after collection. Hematological samples may be placed into ethylenediaminetetraacetic acid (EDTA) or lithium heparin. EDTA is generally preferred for complete blood counts. Blood for plasma chemistry analysis may be placed into a lithium heparin vial. The plasma chemistry samples should be centrifuged immediately to separate the cells from the plasma. If the blood cells are not separated from the cell fraction, than glucose levels may be lower than normal, and phosphorus and potassium levels higher than normal. There are some newer pieces of equipment, such as the Abaxis VetScan (Union City, CA), that can perform a plasma chemistry analysis on a small volume (100 microliters) of whole blood.

The complete blood count routinely includes a packed cell volume, total white blood cell count, and a differential white cell count. The packed cell volume can be used to assess a patient's general health and hydration status. In general, exotic small mammal hematocrits are 30–55. Interestingly, ferrets, which are one of the least active mammals found in captivity, generally have packed cell volumes > 40–45. Anemia in exotic species may be attributed to acute blood loss, chronic infections, malnutrition and toxicities. The erythron of an anemic animal should be evaluated to estimate prognosis. Most laboratories will report alterations in the red blood cell numbers by including information on possible difference in erythrocyte cytoplasmic color (polychromasia) or cell size (anisocytosis). Laboratories generally provide this information using an ordinal scale: 1–4, with 1 being minimal and 4 being a large amount. .

Unlike the lower vertebrates (e.g., birds, reptiles, amphibians, and fish), complete blood cell counts in exotic small mammals can be determined using an automated cell counter. When making differential blood smears, the author prefers to mix 1 drop of 22% bovine albumin (Gamma Biologicals, Inc, Houston, TX, 77092) to 5 drops of blood prior to making a smear to stabilize the cell membranes and improve cell visualization. White blood cell counts for most mammals fall between 5–15 x 10³ cells/microliter; however, white blood cell counts for rabbits (4–10 x 10³) and geriatric ferrets (3–6 x 10³) are generally lower. In both of these species, inflammatory responses are not necessarily characterized by elevated peripheral cell counts, but instead alterations in the cell differential.

Exotic small mammals have the same type of white blood cells seen in domestic mammals: neutrophil, lymphocyte, monocyte, eosinophil, and basophil. One exception is the rabbit, which has a heterophil instead of a neutrophil. The neutrophil (or heterophil in rabbits) is associated with the acute inflammatory response. Monocytes are a common finding in a chronic inflammatory response. In general, the function of the other white blood cells is considered to be similar to those described for other mammals. When interpreting a differential it is important to first determine the primary leukocyte for that species, which will be either the neutrophil or lymphocyte. The proportion of the predominant to the secondary cell will range from 1:1 to 3:1. Alterations in this ratio would be suggestive of an abnormal differential.

A plasma chemistry profile for exotic small mammals generally includes glucose, AST, ALP, ALT, CPK, total protein, albumin, globulin, calcium, phosphorus, potassium, sodium, chloride, blood urea nitrogen, and creatinine.

Plasma glucose levels can be influenced by both intrinsic and extrinsic factors. Hypoglycemia is common in animals offered inappropriate or inadequate diets. The most common cause of hypoglycemia in ferrets is insulinoma, Hyperglycemia in exotic small mammals is rare, although stress, neoplasia, hepatic lipidosis, and pancreatitis have been associated with increased plasma glucose levels.

Tissue and plasma enzymes are routinely used in mammalian patients to assess the function of various body organs. ALP is a non-specific enzyme that can be found in a variety of tissues. Elevations of ALP are common in young fast growing animals or animals repairing a fracture. ALT is generally associated with the liver. This enzyme can be used as an initial screening parameter for the condition of a patient's liver. AST is generally found in muscle and liver, and may be used as a preliminary diagnostic to assess liver function. CPK is consistently found in skeletal, smooth, and cardiac muscle. Elevations of CPK can occur in any disease process that is associated with muscle wasting or destruction.

Plasma total protein values are comprised of two components: albumin and globulin. Hyperalbuminemia is commonly reported in dehydrated animals. Hyperglobulinemia may indicate an infection. A serum electrophoresis can be performed to determine the globulin fraction responsible for the elevated plasma protein. Hypoproteinemia is often reported in cases of malnutrition.

Calcium and phosphorus are the primary plasma chemistry values used to assess renal function in vertebrates. In general, the calcium to phosphorous ratio should be 1.5–2.5:1 (calcium:phosphorus). An inverse calcium to phosphorus ratio may be suggestive of renal disease. The calcium-phosphorus product is a technique described in mammals that is used to assess renal function and the potential for soft tissue mineralization. A calcium-phosphorus product greater than 70 mg/dl is suggestive of renal disease. While this is used in humans to assess the risk for tissue mineralization, its value in exotic small mammals is not known.

Fluctuations in plasma electrolyte values can occur with dietary imbalances, diarrhea, vomiting, and inappropriate laboratory technique. Hypernatremia and hyperchloremia are common sequella to dehydration and dietary over-supplementation. Hyponatremia and hypochloremia may occur in cases of malnutrition. Hyperkalemia is common in renal disease. Hypokalemia may occur in cases of re-feeding syndrome.

Urea is the primary catabolic end product of nitrogen in mammals. Elevations in urea nitrogen can occur with dehydration, renal disease or blockage to the urinary outflow. Creatinine is also used to assess renal function in mammals. These end products of catabolism can be used to assess exotic small mammals using the same techniques described for domestic mammals.