Feline blood types: What you need to know and why (Proceedings)
Dr. Little is the co-owner of Bytown Cat Hospital and Merivale Cat Hospital in Ottawa, Ontario, Canada. She is president of the American Association of Feline Practitioners.
There are three well-known, clinically important blood groups in cats: A, B, and AB.1-2 Despite the nomenclature, the antigens in the feline AB blood group are not serologically related to the human ABO blood group antigens.
Feline Blood Groups
There are three well-known, clinically important blood groups in cats: A, B, and AB.1-2 Despite the nomenclature, the antigens in the feline AB blood group are not serologically related to the human ABO blood group antigens. Another potentially important group called MiK has recently been identified.3 The blood groups are genetically determined species-specific red blood cell surface antigens. The A-allele is dominant over the b-allele so that cats with genotypes A/A and A/b will be type-A, while only the homozygous b/b will have the type-B phenotype. A third type, AB, occurs rarely and expresses both the A and B antigens.4 However, the heritability of type-AB is not well understood.
Various methods are now available to determine blood type, both in a referral laboratory setting and patient-side. Diagnostic laboratories use various serological methods based on agglutination reactions. In addition, genetic testing is now available to identify blood types A and B using buccal swabs, although it cannot distinguish between A and AB blood groups.5 Patient-side testing may be performed with a card typing system (RapidVet®-H, DMS Laboratories, Flemington, NJ). If the card-typing system is used, type-AB and type-B results should be confirmed by a referral laboratory as some cross-reactions have been known to occur.6 A recently introduced option for patient-side blood typing is the gel column agglutination test (DiaMed-Vet® feline typing gel, DiaMed, Switzerland). This test is easier to interpret than the card method, although it requires a specially designed centrifuge that may be cost-prohibitive in some settings.7 An evaluation of various blood typing methods for the cat concluded that the gel column test is reliable when compared to the gold standard Penn tube assay.6
The distribution of feline blood types varies by geographic region and breed (Table 1).8-9 Type-A is the most common type among most cats. There is, however, geographic variation in the prevalence of type-B domestic shorthaired cats. Over 10% of the domestic shorthair cats in Australia, Italy, France and India are type-B. Breed distribution does not vary as much by location because of the international exchange of breeding cats. Over 30% of British Shorthair cats, Cornish and Devon Rex cats, and Turkish Angora or Vans have type-B blood. In contrast, Siamese and related breeds are almost exclusively type-A. Ragdoll cats appear to be unique with regard to blood types. Approximately 3.2% of Ragdoll cats are discordant for blood group when genotyping is compared to serology, necessitating further investigation in this breed.9
Table 1: Selected Blood Type A and B Frequencies in Cats (ignoring AB blood types)
The AB blood type is very rare while the frequency of the MiK blood type is unknown. The presence of red blood cell antigens in addition to the AB group may explain why transfusion compatibility is not guaranteed by blood typing; crossmatching is recommended prior to any transfusion.3 Breeding queens, along with blood donors and, if possible, blood recipients should be blood typed.
Understanding feline blood groups is important because, unlike other mammals, cats produce naturally occurring antibodies, called alloantibodies, against the red blood cell antigens not present on their own cells. The kitten produces these alloantibodies around two to three months of age resulting from the exposure to antigens on plants, bacteria or protozoa that are structurally similar to the red cell antigens. No alloantibodies are produced against antigens that are similar to self-antigens and no previous exposure to blood products (e.g., transfusion or pregnancy) is necessary to produce the alloantibodies. Type-A cats may have low levels of naturally occurring antibodies against blood type-B red cells, but all type-B cats have high levels of naturally occurring anti-A antibodies. Blood type-AB cats do not have alloantibodies.
Transfusion Medicine and Reactions
The indications for the use of blood products are many and include hemorrhage, anemia, hemostatic defects and hypoproteinemia.10 When donors are properly selected and pre-transfusion testing is performed, blood transfusions are well tolerated and effective in cats.11 The Infectious Disease Study Group of the American College of Veterinary Internal Medicine and the Association of Veterinary Hematology and Transfusion Medicine have produced guidelines for infectious disease screening for canine and feline blood donors.12 Many blood products are available or may be prepared, although most veterinary hospitals have access to owned cats for fresh whole blood donation. No universal feline blood donor exists although type-AB cats have been considered universal recipients since they do not have anti-A or anti-B alloantibodies. Recently, however, it has been recommended that type-AB cats be transfused with type-AB or type-A blood. The high titers of anti-A antibodies in type-B blood may result in destruction of recipient red blood cells.2
Both the donor and recipient should be blood typed and crossmatched. Even if the blood types are known, crossmatching should be performed prior to blood administration to avoid incompatible transfusions caused by untested or unknown erythrocyte antigens such as MiK. The risk of an adverse reaction to an unmatched transfusion depends on blood group prevalence and the alloantibody titer of the recipient. Therefore, the risk varies geographically.8 In one study of 126 cats that received blood transfusions, 8.7% suffered acute reactions.13 A crossmatch should be performed again if more than four days have elapsed since the last transfusion from the same donor or if another donor is used since antibody production can occur in as soon as three to four days.
Crossmatching determines the compatibility of donated blood with the intended recipient. For a major crossmatch, red blood cells from the donor blood are tested against the plasma of the recipient. If the recipient's plasma contains antibodies against antigens on donor red blood cells, agglutination will occur. Agglutination indicates the donated blood is incompatible for that specific patient. If no agglutination occurs, the donated blood is considered safe to transfuse. The minor crossmatch determines the likelihood of recipient red blood cell destruction by donor serum. This is a much smaller risk, since the volume of transfused serum is only a small fraction of the patient's total serum volume. Transfusion of whole blood may cause destruction of the patient's red blood cells if the donor blood contains alloantibodies. Importantly, a compatible major crossmatch, minor crossmatch or both does not guarantee red blood cell survival and cannot completely eliminate the risk of a transfusion reaction.
A quick means of performing a major crossmatch is to mix two drops of plasma from the recipient with one drop of anticoagulated blood from the donor on a slide at room temperature.4 The opposite will be a minor crossmatch. Development of macroscopic agglutination within one minute suggests the presence of alloantibodies in the recipient's plasma against donor cells (major crossmatch) or alloantibodies in the donor's plasma against recipient red blood cells (minor crossmatch). In either case, the blood is incompatible. Autoagglutination can make interpretation of the test difficult. Running a control test using saline instead of plasma may help interpretation.
An alternative patient-side method, gel agglutination, is now available for feline crossmatching. Gel tests are less time consuming, standardized, and rely less on the expertise of the operator.7 There are two commercially available products for in-clinic use (DiaMed crossmatch gel, DiaMed; Rapid Vet-H companion animal crossmatch gel, DMS Laboratories).
Adverse effects of blood transfusions can be immunologic reactions to incompatible blood or nonimmune events, and may occur within one or two hours after beginning the transfusion.10,14 Occasionally, they may be seen up to 48 hours later.10 Some reactions are severe enough to cause death. Immune-mediated reactions include hemolysis, allergic reactions, fever, or graft-versus-host reactions.10 Bacterial contamination of the blood product, hemolysis, hypocalcemia (from citrate toxicity), hypothermia, hyperammonemia and volume overload are examples of nonimmune adverse reactions. In either case, the life span of the transfused erythrocytes may be shortened. The half-life of appropriately matched red blood cells in the cat is 29-39 days, but for mismatched transfusions, the half-life may be a matter of hours.
When type-B blood is given to a type-A recipient, the adverse reaction is relatively mild, and includes listlessness, tachycardia and tachypnea occurring within minutes. In this situation, the half-life of the transfused red blood cells is only two days.14 However, if type-A blood is given to a type-B recipient, the reaction is severe and potentially fatal. Transfusion of as little as 1 mL of mismatched blood can cause severe clinical signs, including hypoventilation, apnea, vomiting, diarrhea, vocalizing and arrhythmias.15 The severe inflammatory response may cause signs of shock, multi-organ dysfunction, and disseminated intravascular coagulation. The half-life of the transfused red blood cells is measured in hours.
Despite the best of efforts to prevent them, transfusion reactions may still happen. Depending on the severity, therapy can include glucocorticoids, epinephrine, IV fluids, and discontinuing the transfusion. Fever is usually mild, requiring no treatment. Furosemide should be administered if volume overload occurs. The blood product can be warmed to no more than 37° C if hypothermia occurs. Crossmatching blood is the best means of preventing immune-mediated transfusion reactions even if the blood type is known for both cats. It is also imperative blood be collected and administered as aseptically as possible and cats receiving blood products are monitored carefully.
The strong hemolytic characteristics of the anti-A alloantibodies found in the serum of type B cats is responsible for the often fatal hemolysis that occurs in very young kittens. By understanding the pathologic basis for the disease known as neonatal isoerythrolysis (NI), it is easy to see how it can be prevented. Treatment of the disorder is often unrewarding.
The A allele in cats is dominant to the b allele. Type B queens mated to type A or AB toms will likely have kittens that have expressed type A (or AB) antigens on their erythrocytes. Because the placenta in cats is impermeable to the passage of immunoglobulins, in-utero hemolysis does not occur. Once born, however, passive absorption of proteins from the colostrum, including anti-A antibodies, occurs for the first 12 to 24 hours. The exposure to the strongly hemolyzing anti-A antibodies in the colostrum of type-B queens leads to massive, often fatal erythrocyte destruction in type A and AB kittens.16 The severity of signs is related to the amount of colostral antibody absorbed prior to closure of the kitten's intestinal tract to passive immune transfer. Once the kitten gains the ability to digest proteins, it is no longer at risk for neonatal isoerythrolysis. When this occurs varies among individuals.
Kittens at risk are born healthy and only become ill after consuming anti-A antibodies in colostrum. Clinical signs appear within the first few hours to days of life and may range in severity from sudden death, to kittens that develop tail-tip necrosis from vessel obstruction by agglutinating erythrocytes. Some kittens develop dark colored urine. These kittens may also stop nursing; fail to thrive or gain weight; develop anemia and icterus; and usually die within the first week after birth. The diagnosis is confirmed by blood typing the queen and affected kittens.
Because of the acute nature of the disease, therapy is usually unsuccessful. The kitten should be removed from the queen for the first 18-24 hours after birth and body temperature should be well controlled. Affected kittens may be transfused with 5-10 mL washed type-B red cells via intravenous or intra-osseous catheter.17 Ideally the donated blood will come from the queen as she will not have antibodies against her own red blood cells. Type-B blood is used since the only alloantibodies present in the newborn kitten are the anti-A antibodies from the queen's colostrum; they have not yet made any of their own alloantibodies. Kittens start to produce their own anti-B alloantibodies soon after birth. If a further transfusion is necessary three days after birth, use type-A blood.
Preventing the disorder, however, is much more successful than the treatment. Blood typing of breeding pairs in breeds known to have a high percentage of type-B cats will identify pairings that could produce kittens at risk of NI. If it is necessary to breed a type-B female to a type-A or AB tom, plans should be made to foster the kittens to a type-A queen for the first 18-24 hours of life. If a suitable foster queen is not available, the kittens can be fed kitten milk replacer for the first 18-24 hours. Alternately, if the breeder can be present at the time of birth, patient-side blood typing cards may be used to type umbilical cord blood from the kittens before they have a chance to nurse. Only kittens at risk of NI (type A or AB) are then removed from the queen for 18 hours, and type-B kittens are allowed to remain with the queen. Care must be taken to avoid cross-contamination with blood from the queen in birth fluids. Type-B kittens receiving anti-B antibodies from the colostrum of type-A queens are not known to be at risk of developing NI.
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