Feline Anemias-Therapeutic Options and Transfusion Therapy
Urs Giger, Diplomate, ACVIM & ECVIM
University of Pennsylvania
Philadelphia, PA, USA
The identification of the various causes of feline anemia is a diagnostic challenge and has been reviewed in the previous chapter on Feline Anemia-a Diagnostic Challenge. Some of the therapeutic options for various specific diseases were also mentioned there and will be discussed here. However, this presentation will center on the supportive care with blood products.
Transfusion therapy has taken an increasingly important role in the life support of cats. Over the past decade the use of blood products in treating critically ill animals has drastically increased. At the Veterinary Hospital of the University of Pennsylvania alone approximately 350 units of blood are being transfused to mostly anemic and bleeding cats per year. A closed feline blood collection system has been developed that allows for blood component preparation and storage. Furthermore, the need for blood typing and cross matching as well as testing of donors for transmittable diseases has now been recognized in order to assure safe and more efficacious transfusions. Recent advances in blood compatibility testing in cats are reviewed and practical recommendations are made.
The AB blood group system is the only one recognized in cats and consists of three blood types: type A, type B, and type AB. Their inheritance pattern is unique and of considerable importance to breeders with respect to neonatal isoerythrolysis (NI). The A allele is dominant over the B allele. Thus, only homozygous B/B cats express the type B antigen on their erythrocytes. Type A cats are either homozygous (A/A) or heterozygous (A/B) for the A allele. Finally, the rare AB blood type is separately inherited as a third allele that is recessive to A and codominant to B. The frequency of feline A and B blood types varies geographically and among breeds. Although type A is the most common blood type, the frequency of type A and B in domestic shorthair cats varies worldwide and even among regions. Depending on the breed the type B frequency may vary from none, as in the Siamese and related breeds, to 40% as in the British and Exotic shorthair as well as Devon and Cornish Rex breeds. In contrast, type AB is extremely rare, less than 1% in domestic shorthair and some purebred cats, particularly in certain families.
In contrast to dogs, cats possess naturally occurring alloantibodies (also known as isoantibodies) against the blood type antigen they lack. In particular, all type B cats develop very strong anti-A antibodies with high hemolysin and agglutinin titers (>1:32 and in some cases reaching 1:2000) after a few weeks of age. These anti-A antibodies are responsible for the life-threatening incompatibility reactions such as neonatal isoerythrolysis and acute hemolytic transfusion reactions.
A mismatched transfusion with type A blood given to a type B cat will result in a very serious acute hemolytic transfusion reaction. A first transfusion and as little as one milliliter of incompatible blood may cause a fatal reaction without prior sensitization. Affected cats may show anaphylactic signs of hypotension, bradycardia, vomiting, and convulsions followed by hemolytic signs of pigmenturia and icterus without transfusion-associated rise of the hematocrit. Thus, mismatched transfusions are dangerous as well as ineffective. Hemolytic transfusion reactions are difficult to manage and no specific protocol has proven effective.
The A and AB kittens receiving anti-A alloantibodies through the colostrum from type B queens, including primiparous queens, during the first day of life are at risk for neonatal isoerythrolysis. Hemolysis of the newborn is characterized by dark pigmenturia, anemia, icterus, anorexia, and sudden death within the first week of life.
In contrast to type B cats, type A cats have generally weak anti-B alloantibodies with low anti-B titers of 1:2. These antibodies cause shortened survival of transfused B cells in type A cats with relatively mild signs of acute hemolytic anemia. However, these anti-B antibodies have not been associated with neonatal isoerythrolysis in type B kittens born to type A queens.
Table 1. Blood type A and B frequency in cats
*breeds with isolated type AB cats
Because of the strong antigenicity of the type A and type B erythrocytes, typing of donors and patients as well as breeding animals is strongly recommended. Serum from type B cats containing alloantibodies against A cells or anti-A monoclonal antibodies and a lectin (Triticum vulgaris) or anti-B monoclonal antibodies serve as anti-A and anti-B reagents and produce strong agglutination reactions with type A and type B blood, respectively. A simple blood typing card is available to classify cats as type A, B or AB (DMS Laboratories, 2 Darts Mill Road, Flemington, NJ 08822, 1-800-567-4DMS). The current assay requires a small amount of anticoagulated blood (0.1 ml) and is based on an agglutination reaction that occurs within 2 minutes when erythrocytes that are either A or B positive interact with the anti-A antibody or anti-B lectin. Feline blood typing is also available through most commercial and veterinary school laboratories including the author's laboratory, which has typed over 13,000 cats. Blood that is typed as AB should be confirmed in a reference laboratory that uses a tube assay, because unspecific agglutination may mimic the rare AB blood type. Typing is recommended 1) for feline donor and recipient cats in order to administer only matched transfusions and 2) for breeding cats to assure blood-compatible mates and avoid neonatal isoerythrolysis.
Caution should be exercised whenever the blood is autoagglutinating or has a very low hematocrit (<10%). It is recommended to check for autoagglutination of blood with saline on a slide or with the special typing cards to check for autoagglutination (available from the manufacturer). Autoagglutinating blood (as seen sometimes with FeLV positive blood) may be first washed 3 times with saline. However, true (persistent) autoagglutination precludes typing because it will always look like type AB positive blood on the card or tube assay. Finally, blood from very anemic cats may not agglutinate when exposed to the reagents because of a prozone effect. In these cases some of the patient's plasma may be discarded before applying a drop of blood onto each well on the card.
Whereas blood typing tests reveal the blood group antigens on the red blood cell surface, blood crossmatching tests discover the serologic compatibility or incompatibility between donor and recipient. Thus, the crossmatch test checks for the presence or absence of naturally occurring alloantibodies as well as alloantibodies induced by previous transfusions in serum (or plasma); these alloantibodies may be hemolyzing and/or hemagglutinating and can be directed against known blood groups or other red blood cell surface antigens. The major crossmatch tests for alloantibodies in the recipient's plasma against donor cells, whereas the minor crossmatch test looks for alloantibodies in the donor's plasma against the recipient's red blood cells. Autoagglutination or severe hemolysis may preclude the crossmatch testing. A major crossmatch incompatibility predicts that the transfused donor cells will be attacked by the patient's plasma thereby causing an acute hemolytic transfusion reaction that could be life-threatening. A minor crossmatch incompatibility indicates that the donor's plasma attacks the patient's red cell. It is important to recognize that the prediction and interpretation of crossmatch test results are different between dogs and cats.
Because of the presence of naturally occurring alloantibodies in cats, an initial crossmatch test result before the first transfusion can be incompatible. Furthermore, based upon the crossmatch results and knowledge of the donor blood type, one might be able to predict the blood type of the patient. If the major crossmatch is strongly incompatible, the recipient is likely a type B cat and the donor has type A (or AB) blood (because of the recipient's strong anti-A). If the minor crossmatch is strongly incompatible, the recipient is likely a type A (or AB) cat and the donor has type B blood (because of the donor's strong anti-A). Finally, if both crossmatches are compatible, donor and recipient have the same blood type. Thus, if blood typing is not available in a timely fashion, at least a crossmatch test should be done. Due to strong anti-A agglutinins, blood type incompatibilities in cats can be recognized by a simplified crossmatch procedure mixing two drops of plasma with one drop of blood from either recipient or donor on a slide at room temperature. The development of macroscopic agglutination within a minute would document an A-B incompatibility.Urs Giger, ACVIM & ECVIM
University of Pennsylvania
Philadelphia, PA, USA