Chapter 25
Small Mammal Transfusion Medicine
Jody Nugent-Deal and Kristina Palmer
William R. Pritchard Veterinary Medical Teaching Hospital, University of California, Davis, California, USA
Introduction
Exotic small mammals such as ferrets, rabbits, and rodents are popular companion animals. Due to their popularity as household pets, veterinary professionals are often called upon to provide advanced veterinary care including, but not limited to, administering blood transfusions. Given the paucity of information in the veterinary literature pertaining to transfusion medicine in exotic species, common principles of blood transfusion medicine and blood substitute therapy in mammals such as dogs and cats can sometimes be extrapolated to exotic small mammals. However, the difficulties of catheter placement, shortage of blood products, and challenging blood collection techniques discourage many clinicians from performing transfusions in exotic pets. Further studies are needed to gather information about exotic animal transfusion medicine. Although there is sometimes little choice, caution should be taken when using blood substitutes and providing whole blood transfusions to these animals.
Indications for transfusions
Blood transfusions are generally indicated to replace a deficiency of blood constituents such as red blood cells (RBCs), plasma, clotting factors, and platelets. Frequently, the need for blood transfusions is acute, such as with hemorrhage due to trauma, surgery, or massive hemorrhage resulting in hypovolemia. Currently, the only option for exotic small mammals is a whole blood transfusion. Acute blood loss between 20% and 30% of the total blood volume in most patients is considered critical and will likely necessitate a transfusion. Other conditions sometimes requiring blood transfusions include, but are not limited to, coagulopathies, hypoproteinemia, decreased oxygen-carrying capacity, hemolysis secondary to hemolytic anemia (e.g., lead toxicosis), immune-mediated diseases, reduced hematopoiesis associated with chronic kidney disease, toxin exposure, and neoplasia (Box 25.1).
The decision to transfuse a patient should be based on the packed cell volume (PCV), clinical status of the patient, disease process, and availability of species-specific blood products. Reference ranges for PCV are available for all major groups of companion exotic small mammals (Table 25.1). In most cases, a transfusion is considered when the PCV decreases below 20%,
Table 25.1 Reference range for packed cell volume in companion exotic small mammals (Carpenter 2013)
Small mammal | Reference range (%) |
Ferret | Male 36–50, female 47–51 |
Rabbit | 30–50 |
Guinea pig | 35–45 |
Chinchilla | 27–54 |
Rat | 35–45 |
Mouse | 35–40 |
Hamster | 45–50 |
but the patient’s clinical status must also be considered, especially in patients with chronic conditions (Lichtenberger and Lennox 2012).
Donor selection
Proper donor selection is pertinent for a successful transfusion. It is important to ensure that the donor is a healthy young to middle-aged adult in good body condition. Ideally, donors are male or nulliparous females. The donor should have no previous history of blood transfusions or transmissible diseases. With the exception of ferrets, most exotic small mammals do not have standard vaccination protocols. Donor ferrets should be fully vaccinated prior to donation. Lastly, and arguably most importantly, the donor should be the same genus and species as the recipient. RBC destruction and transfusion reactions are greatly increased when blood from one species is transfused into another species (e.g., rabbit to mouse) (Lichtenberger 2004). Proper donor selection in any species will minimize the risk of transfusion-associated complications, including reactions.
Donor evaluation
A thorough physical examination, complete blood count, and biochemistry profile should be performed prior to donation. Blood values should be within normal limits, including a PCV >40% (Lichtenberger 2004). In some cases, a patient might be too small to perform a complete blood count and biochemistry panel prior to donation. When this is the case, minimally, a PCV, total solids, blood glucose, and blood urea nitrogen should be performed.
A comprehensive physical examination should be performed prior to blood collection. The exotic small mammal physical examination is performed similarly to that in dogs and cats. All items needed to perform the physical examination should be within arm’s reach before the patient is removed from the enclosure. Exotic small mammals can become easily stressed, therefore it is essential to keep the “time in hand” to a minimum. A visual physical examination should be performed prior to removing the patient from the cage or carrier. The visual examination will allow assessment of the overall mentation of the animal.
The physical examination is often started by first obtaining the patient’s weight and temperature. Many exotic small mammal patients are less than 2–4 kg, therefore it is best to use a gram or pediatric scale that can provide accurate weights to 1 gram. Obtaining a temperature can be challenging, but a rapid digital thermometer is generally the quickest and best method (unless the patient is too small).
The authors prefer the head-to-tail method for the hands-on portion of the examination. This will help ensure nothing is overlooked. It is important to obtain both a heart and respiratory rate as soon as the animal is removed from the cage. Normal physiologic values are available for all common companion exotic small mammals (Table 25.2). If the respiratory rate seems exaggerated, repeat the rate upon completion of the examination and after the animal has been placed back into the cage. The ears and eyes are assessed using an otoscope and ophthalmoscope. The primary deviation from the head-to-tail method of physical examination in exotic small mammals is the oral examination. In dogs and cats, the mouth is generally examined when the head is examined. The oral examination can be very stressful for exotic small mammals (ferrets are the exception) and therefore is generally done last. A complete oral examination is not typically performed on patients prior to donation, but is suggested as part of the yearly comprehensive examination.
Table 25.2 Normal physiologic values for common exotic small mammals (Ballard and Cheek 2010)
Species | Heart rate | Respiratory rate | Rectal temperature | Adult weight | Life span |
Rat | 250–450 bpm | 90 bpm | 35.9–37.5°C (96.6–99.5°F) | 250–520 g | 2–4 years |
Mouse | 300–750 bpm | 70–120 bpm | 36.7–38.3°C (98–101°F) | 20–40 g | 1–3 years |
Ferret | 180–250 bpm | 10–30 bpm | 37.8–40°C (100–104°F) | Male 1–2 kg, female 600–950 g | 5–8 years |
Chinchilla | 150–350 bpm | 40–80 bpm | 37–38°C (98.5–100.4°F) | 400–700 g | 8–10 years |
Guinea Pig | 230–300 bpm | 70–130 bpm | 37.2–39.5°C (99–103.1°F) | 700–1200 g | 5–8 years |
Hamster | 300–500 bpm | 60–220 bpm | 37–38.6°C (98.6–101.4°F) | 85–150 g depending on breed | 18–24 months |
Rabbit | 200–300 bpm | 30–60 bpm | 38.3–40°C (101–104°F) | 700 g to >6 kg depending on breed | 5–12 years depending on breed |
The hydration status of the patient should be evaluated during the physical examination. The mucous membranes should be moist and pink. As with most other mammals, the capillary refill time should be between 1 and 2 seconds. Signs of dehydration include dry or tacky mucous membranes, sunken eyes, and lack of skin turgor. The skin should be tented or pulled upward to assess dehydration. The longer the skin stays in place or stays “tented”, the more dehydrated the animal is. Percentages of dehydration can be assigned to the patient in the same manner as dogs and cats. For example, a patient with slightly tacky mucous membranes and skin that is only slightly slow (instead of immediate) to return to normal turgor can be assigned a 5% dehydrated. A patient with any signs of dehydration should not be used for donation.
The heart and lungs should be auscultated using an infant or pediatric stethoscope (Figure 25.1). It is important to note the presence of any heart murmurs, arrhythmias, or harsh lung sounds. Auscultation is performed in the same manner as would be performed on a dog or cat. A body condition score should also be assigned to the patient. The same system used for dogs and cats is also used with exotic small mammals (1 to 9 scale), with a 1 out of 9 being emaciated and 9 out of 9 being severely obese. Lastly, the entire body is visually examined and thoroughly palpated for any masses or other abnormalities.
Blood types
Blood types are defined by inherited antigens located on the surface of RBCs. The antigens are made up of various substances such as carbohydrates, proteins, glycoproteins, and glycolipids. These genetic markers are species-specific and vary in immunogenicity and clinical significance. Antigens contribute to the recognition of self. They elicit the production of antibodies once introduced into the circulation of an animal lacking these antigens. It is ultimately the antibodies in the serum of the recipient that have the ability to bind to these antigens, which will lead to acute or delayed hemolytic transfusion reactions.
To date, many species have documented blood types including primates, birds, dogs, and cats. While a great deal of information exists in these species, research is lacking in most exotic animals. The domestic chicken has been vastly studied, with 28 blood groups identified in this species (Hohenhaus 2004). Unfortunately, blood types have not been described in other companion or wild birds, nor have they been described in most exotic small mammals. Blood groups have not been vastly studied or identified in rabbits, guinea pigs, chinchillas, or rats.
The European or domestic ferret (Mustela putorius furo) is unique among the mammals that have been studied. The serum and RBCs of 212 randomly paired ferrets was examined and revealed no evidence of naturally acquired blood group antibodies. Six pairs of ferrets were transfused twice, 34 days apart, and all ferrets were tested 21 days after the first transfusion and then 10 and 30 days after the second transfusion. At no point were RBC antibodies detected; therefore, blood groups found in other animals either do not exist in the domestic ferret or represent antigen systems too weak to elicit measurable responses. This information suggests that transfusions in ferrets pose little clinical risk, even without crossmatching, because they have no detectable blood group antigens or antibodies (Manning and Bell 1990).
Crossmatching
Because blood transfusions have the potential to introduce foreign antigens upon administration to the recipient, crossmatching should ideally be performed in all patients prior to transfusion. Due to the lack of knowledge regarding blood types in most species of exotic small mammals, crossmatching is recommended prior to transfusion, especially when previous transfusion history is unknown.
Crossmatches are agglutination and hemolysis tests performed to assess donor–recipient compatibility, observing interactions between the donor and recipient RBCs and antibodies contained in the plasma. A major crossmatch detects the presence of pre-existing antibodies in the recipient’s plasma that could produce an immunologic reaction. Pre-existing antibodies could be either naturally occurring or antibodies produced after a previous incompatible transfusion. In ferrets, attempts have been made to induce an antibody response experimentally, with no success (Manning and Bell 1990; Hillyer 1995). Sensitization after blood transfusion has not been well studied in other exotic small mammals.
Since naturally occurring alloantibodies or induced antibodies have not been identified in the domestic ferret, an immunologic transfusion reaction is unlikely to occur, and multiple transfusions from the same donor can be administered without a crossmatch. Because other exotic small mammal species have not been well studied, it is advisable to perform a crossmatch prior to administering any blood transfusion. A compatible crossmatch reduces, but does not eliminate, the risk of a transfusion reaction; therefore, patients must still be monitored closely during and immediately after the transfusion.
Major and minor crossmatch
The major crossmatch is a serologic method designed to determine the compatibility between the donor RBCs and the recipient plasma. The main purpose of the test is to help prevent incompatible transfusions that could result in immunologic transfusion reactions. The major crossmatch is more clinically significant in exotic small mammals. To perform a major crossmatch, a small amount of the recipient’s plasma is incubated with a small amount of the donor’s RBCs. The mixture is observed for visible and microscopic agglutination or hemolysis. If an agglutination reaction or hemolysis occurs, an incompatibility exists and the donor’s RBCs should not be used for the transfusion.
A minor crossmatch is the serologic method designed to determine the compatibility between the donor plasma and the recipient RBCs. The transfusion of plasma-containing components (e.g., whole blood, fresh frozen plasma) has the potential to cause destruction to the recipient’s RBCs. Destruction occurs if the donor plasma has antibodies directed against an RBC antigen on the recipient’s RBCs. The minor crossmatch is performed by mixing a small amount of the recipient’s RBCs with a small amount of the donor’s serum. The mixture is then examined under a microscope. If the RBCs are agglutinated, then the results are incompatible. This test is of less clinical significance as it is less common for donors to have antibodies against recipient RBCs if not previously sensitized by a transfusion.
Simplified crossmatch
Comprehensive crossmatching procedures performed in dogs and cats typically require up to 2 mL of blood anticoagulated in ethylenediaminetetraacetic acid (EDTA). Due to the size of most exotic small mammals, this is usually impossible, especially if the patient is already critically ill, anemic, or requiring a surgery with a large amount of blood loss anticipated. In such cases, a simplified crossmatch can be performed (Box 25.2). This is completed by mixing 2 drops of plasma from the recipient with 1 drop of blood from the donor on one slide. On a second slide, 2 drops of plasma from the donor are mixed with 1 drop of blood from the recipient. Both slides are examined under a microscope. Macroscopic agglutination within 1 minute suggests an incompatibility between the donor and recipient. This simplified crossmatch predicts potential agglutination, but it cannot predict hemolysis (Lichtenberger 2004).
It is important to remember that a compatible major or minor crossmatch does not guarantee normal RBC survival, nor does it completely eliminate the risk of a transfusion reaction. Delayed transfusion reactions or reactions to donor leukocytes or plasma proteins are not detected by crossmatching.
Blood collection and common venipuncture sites
Blood collection can be difficult in exotic small mammals, especially when a large amount of blood is needed for a transfusion. It is imperative that staff are properly trained and comfortable with handling, restraint, and various species-specific venipuncture sites. Table 25.3 lists common venipuncture sites for companion exotic small mammals. Most donors will need to be heavily sedated or anesthetized for large-volume blood collection. Because these patients are so small, a traditional blood collection system cannot be used for collection, storage, and administration. Instead, a hypodermic or butterfly needle attached to a sterile syringe with anticoagulant is used to collect blood (Lichtenberger 2004).
Table 25.3 Common blood collection sites in common exotic small mammals
Ferrets | Jugular vein Cranial vena cava |
Rabbits | Jugular vein Lateral saphenous vein |
Guinea pigs | Jugular vein Femoral vein Cranial vena cava |
Chinchillas | Jugular vein Cranial vena cava |
Small rodents | Jugular vein Femoral vein Cranial vena cava |
How much blood is it safe to collect?
Exotic small mammals are generally very small, with most species weighing <4 kg. While blood volume varies by species, it is generically estimated that circulating blood volume is about 6–7% of the donor’s body weight (Lennox and Bauck 2012). In a healthy adult animal, it is imperative that no more than 10% of the blood volume be collected within a 30-day period (Box 3). Table 25.4 illustrates the estimated blood volume of many common companion exotic small mammals, as well as safe blood collection volumes.
Table 25.4 Estimated circulating blood volume in common exotic small mammals
Species | Estimated blood volume (mL/kg) | Collection volume limit (10% of estimated blood volume) (mL/kg) |
Ferret | 60 | 6 |
Rat | 65 | 6.5 |
Mouse | 75 | 7.5 |
Guinea pig | 70 | 7 |
Hamster | 80 | 8 |
Rabbit | 55 | 5.5 |
Source: University of Pittsburgh Policy for Regulating the Volume of Experimental Blood Sample Withdrawals in Laboratory Animals, https://www.iacuc.pitt.edu/sites/default/files/documents/Blood%20Volume%20Withdrawal%20Policy.pdf