In cats, blood loss anemia and erythropoiesis deficiency are the main indications of transfusion.¹ Recent discoveries and technological advancements will be discussed, as well as practical recommendations.

Red Blood Cell Antigens and Blood Groups in the Cat

Cat AB Blood Group System

The AB blood group system is the predominant blood group system in cats. Three phenotypes occur: type A, type B, and type AB. Approximately one-third of type A cats have alloantibodies in their plasma capable of weak macroscopic agglutination of type-B RBC. Of major clinical significance is the fact that all type B cats have strong anti-A naturally occurring alloantibodies. Type AB cats do not possess alloantibodies against either A or B antigens.

Genetics

The blood group antigens A and B are inherited as simple autosomal Mendelian traits with A being dominant to B. In spite of extensive breeding experiments and pedigree analysis, the mode of inheritance of the AB phenotype remains unclear due to apparently different inheritance patterns in different breeds.² The ab allele, causing blood type AB, was found to be separately inherited, being (co)-dominant to b and recessive to the A allele.³Thus, all type B cats are homozygous for the b allele (genotype b/b), type A cats can be either homozygous (genotype A/A) or heterozygous (genotype A/b or A/ab), and the rare type AB cats can either be homozygous (genotype ab/ab) or heterozygous (genotype ab/b).

Incidence of the Antigens

The percentage distribution of types A and B in domestic cats can vary markedly with geographic location worldwide. Type B domestic cats are uncommon in some countries like the United States and Switzerland; however, in other countries such as Australia, Greece and Turkey, their prevalence can reach up to 36% of the non-pedigree feline population. Similarly, the variation per breed is significant. For instance, the incidence of type B in the United States ranges from 0% up to 60% among different purebred cats.

To this day, type B has not been documented in Siamese cats worldwide. In opposite, breeds such as Turkish Van and Angora cats are reported to have a prevalence of type B cats of 60% and 46.4%, respectively.

Type AB is exceedingly rare and only found in breeds in which type B is detected.² In a survey of cats in the United States and Canada, 13 of 9,239 cats (0.14%) were type AB.² Similarly, only 7 of 1895 cats (0.4%) were type AB in a survey conducted in Australia. Type AB has, however, been reported more frequently in certain random bred populations, such as in specific surveys from Israel (14.5%), in Japan (9.7%), in Portugal (6.3%) and in England (8.5%). Compared to all other cat breeds, Ragdolls are commonly type AB (frequency in Italy: 18–24%).

Molecular Characterization of the Antigens

The A and B blood types of cats are caused by differences in the neuraminic acid residues present on a ceramide dihexose backbone on the RBC membrane. Type A RBCs have mainly N-glycolylneuraminic acid (NeuGc), while N-acetylneuraminic acid (NeuAc) is the determinant of the B antigen. The lectin from Triticum vulgaris (wheat) will bind selectively with NeuAc and can be used to identify RBC expressing the type B antigen. Type AB cats have both NeuAc and NeuGc present on the RBCs in similar quantities, each at approximately 50% normal expression levels.

Molecular Genetics

Cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) is the enzyme that catalyzes the conversion of NeuAc (type B antigen) to NeuGc (type A antigen).The discovery of polymorphisms in CMAH ascribed to type B has allowed the development of commercially tests to identify the AA, Ab and bb genotypes. However, the assays have the significant limitation of not being able to differentiate between type A and type AB cats.⁴ In addition, many examples of phenotype-genotype discordances for cats with type B and AB blood have been reported.⁵ More recently, novel variants in CMAH have been identified in Ragdolls and other breeds, and represent a promising diagnostic scheme to genotype all cats (i.e., differentiating type A, type B and type AB).^3,5

The Mik Antigen

Based on the presence of a naturally occurring alloantibody, the Mik blood group system was described in 2007.⁶ The clinical relevance of anti-Mik alloantibodies was documented after an acute hemolytic transfusion reaction following inadvertent transfusion of Mik-positive blood to a thereafter confirmed Mik-negative cat upon its first blood transfusion.⁶ Unfortunately, anti-Mik antibodies are no longer available.

Feline Blood Collection

Blood Donor Selection and Blood Collection

Feline donors should ideally weigh >4.5 kg and healthy indoor adult cats. They should be tested for transfusion-transmissible infectious agents, such as FIV, FeLV, Mycoplasma haemofelis and Bartonella henselae.⁷ Deep sedation/anesthesia is almost always required. About 10–15 ml/kg of blood can be collected (i.e., a total of 40–60 ml). No closed collection system suitable for cats is commercially available. Most commonly, an 18–19G butterfly needle connected by a three-way valve to 20–30 ml syringes containing CPDA-anticoagulant is used. Since this constitutes an open-collection system, the blood collected should be used either immediately (whole fresh blood) or stored at 4°C and used within 24 hours to limit the risk of bacterial contamination. That said, if the sample is taken according to strict aseptic rules and non-essential manipulations of the product are avoided, many veterinary centers store it for a period of 20 days.

Feline patients are most often transfused using whole blood. That said, the separation of whole blood into components (RBC concentration and plasma) is quite feasible, even using simple sedimentation. Using RBC concentrate should be strongly considered in cardiac patients and in cats requiring more than one blood transfusion.

Volume administered (ml) = Weight (kg) x 70 ml/kg (cat) x (Desired PCV - PCV of recipient)/PCV of blood unit

In contrast to findings in dogs, transfusion of feline RBCs using a syringe and microaggregate filter, compared to gravity, does not significantly impact short- or long-term survival of the transfused cells.⁸

Transfusion Reactions and Importance of Blood Typing

Of utmost clinical significance is the presence of highly potent anti-A antibodies in virtually all type B cats, which can result in severe acute hemolytic transfusion reaction, and even death, if type A blood is administered to a type B cat. This highlights the importance of performing blood typing of donors and recipients, which is facilitated by commercially available typing kit for the AB system in cats (RapidVet-H® feline or IC; feline Alvedia®).

Naturally Occurring Alloantibodies Outside of the AB System and Importance of Crossmatching

In recent literature, there is some evidence for the presence of other naturally occurring alloantibodies outside the AB blood group system, like anti-Mik.^9,10 As such, McClosky et al. documented major crossmatch incompatibilities outside of the AB system in 23 of 154 transfusion-naïve cats (14.9%).¹⁰ Similarly, Sylvane et al. identified 10 of 52 major crossmatches performed in transfusion-naïve cats to be incompatible (19%).¹¹ However, the crossmatch screening of 112 cats in the United Kingdom failed to detect any non-AB incompatibilities.¹² In a prospective controlled study, 48 transfusion-naïve anemic cats were randomized to receive either a type- and crossmatch-compatible packed RBCs transfusions or non-crossmatched blood type compatible pRBCs. No difference in the increase in PCV after transfusion or in the incidence of transfusion reactions were detected between groups; however, crossmatched-incompatible cats were not included (i.e., transfused) for obvious ethical reasons.¹¹

Other RBCs antigens outside of the AB blood group system can also be suspected based on the prevalence of non-AB RBC incompatibilities in previously transfused cats, which has been reported to be approximately 25–27%.^9,10 Again, the clinical significance of such alloantibodies remains unknown.

References

1.  Klaser DA, et al. Red blood cell transfusions in cats: 126 cases (1999). J Am Vet Med Assoc. 2005;226(6):920–3.

2.  Griot-Wenk ME, et al. Blood type AB in the feline AB blood group system. Am J Vet Res. 1996;57(10):1438–42.

3.  Kehl A, et al. Molecular characterization of blood type A, B, and C (AB) in domestic cats and a CMAH genotyping scheme. PLoS One. 2018;13(9):e0204287.

4.  Bighignoli B, et al. Cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) mutations associated with the domestic cat AB blood group. BMC Genet. 2007;8:27.

5.  Gandolfi B, et al. A novel variant in CMAH is associated with blood type AB in Ragdoll Cats. PLoS One. 2016;11(5):e0154973.

6.  Weinstein NM, et al. A newly recognized blood group in domestic shorthair cats: the Mik red cell antigen. J Vet Intern Med. 2007;21(2):287–92.

7.  Wardrop KJ, et al. Update on canine and feline blood donor screening for blood-borne pathogens. J Vet Intern Med. 2016;30(1):15–35.

8.  Heikes BW, Ruaux CG. Effect of syringe and aggregate filter administration on survival of transfused autologous fresh feline red blood cells. J Vet Emerg Crit Care. 2014;24(2):162–7.

9.  Weltman JG, et al. Influence of cross-match on posttransfusion packed cell volume in feline packed red blood cell transfusion. J Vet Emerg Crit Care. 2014;24(4):429–36.

10.  McClosky ME, et al. Prevalence of naturally occurring non-AB blood type incompatibilities in cats and influence of crossmatch on transfusion outcomes. J Vet Intern Med. 2018;32(6):1934–42.

11.  Sylvane B, et al. Effect of cross-match on packed cell volume after transfusion of packed red blood cells in transfusion-naive anemic cats. J Vet Intern Med. 2018;32(3):1077–83.

12.  Tasker S, et al. Feline blood genotyping versus phenotyping, and detection of non-AB blood type incompatibilities in UK cats. J Small Anim Pract. 2014;55(4):185–9.