Blood groups are determined by species-specific, inherited antigens (glycoproteins or glycolipids) present on the surface of red blood cells.
CLASSIFICATION
The main classification system for blood groups in the dog is called the Dog Erythrocyte Antigen (DEA) system and includes DEA groups 1.1, 1.2, 1.3, 3, 4, 5, 6, 7 and 8. These groups can be characterized in vitro through the use of species-specific antiserum. In Japan a new classification, based on four monoclonal antibodies (Shigeta A, B, D and E), has been proposed, but it is not clear whether this correlates with the DEA classification. Only group A seems to correspond to DEA 3.
Some of the characteristics of the different blood groups, their spread within the canine population (the data refer to the incidence in the USA) and the problems related to possible transfusion reactions are discussed below.
DEA 1.1 is present in 45% of dogs, while the incidence of DEA 1.2 is 20%. Naturally circulating antibodies have not been reported for either blood group. After sensitisation with DEA 1.1-positive red blood cells, DEA 1.1/1.2-negative dogs develop antibodies which, if the dog is subsequently transfused with DEA 1.1/DEA 1.2-positive red blood cells, will cause elimination of the transfused red blood cells within 12-24 hours.
DEA 1.3 has been reported only in Australia and is not associated with natural antibodies in the circulation. No experimental studies on transfusions involving this blood group have been reported.
DEA 3 has been reported in 6% of dogs and natural antibodies have been found in 20% of DEA 3-negative dogs. The administration of DEA 3-positive red blood cells to a previously sensitised dog is followed by the loss of the transfused red blood cells within 5 days.
DEA 4 is present in more than 98% of dogs. Natural occurring antibodies have not been reported, while possible transfusion reactions associated with this blood group remain to be defined clearly. DEA 4-negative dogs produce antibodies if transfused with DEA 4-positive red blood cells. Immunised dogs do not, however, have loss or haemolysis of erythrocytes if transfused with DEA 4-positive red blood cells. There is a case report of a haemolytic reaction occurring after repeated transfusions of DEA 4-positive blood to a DEA 4-negative dog.
The incidence of DEA 5 is low and 10% of untransfused animals have circulating antibodies to this blood group antigen. The transfusion of DEA 5-positive blood to a previously immunised dog gives rise to the sequestration and loss of the red blood cells within 3 days.
DEA 6 is present in 100% of dogs. No cases of naturally circulating antibodies have been documented, while rapid removal of DEA 6-positive red blood cells transfused into a previously sensitised DEA 6- negative dog has been observed.
DEA 7 has been reported to be present in 40-54% of dogs. The antigen defining this group (Tr antigen) is not a true membrane antigen but is thought to be produced elsewhere in the body, secreted into the plasma and adsorbed onto the surface of the red blood cells. DEA 7 is associated with the presence of low-titre, non-haemolytic, weak antibodies in 20-50% of DEA 7-negative subjects. Furthermore, DEA 7-negative subjects sensitised by DEA 7-positive red blood cells show sequestration and loss of the erythrocytes within 72 hours of the transfusion of more DEA 7-positive red blood cells.
DEA 8 has been observed in 40-45% of dogs. The DEA 8 antigen (He antigen) has only been described: there is no information on the possible existence of natural antibodies or antibodies formed in transfusion reactions.
In 2007 a new antigen, named Dal, was reported. The alloantibody against this antigen was described for the first time in a Dalmatian dog immunised by previous transfusions.
The antigens characterizing the blood groups are able to cause an important production of antibodies (IgM and IgG) with haemolytic and red blood cell agglutinating effects. The serum of dogs that have never received a transfusion can contain natural alloantibodies against the blood group antigens, but the clinical significance of these antibodies seems to be limited. From a clinical point of view the blood group which seems to be most antigenic is DEA 1.1. Pre-formed alloantibodies to the antigen have not been identified, whereas naturally occurring antibodies have been recorded in 10%, 30% and 50% of dogs with blood groups DEA 3, DEA 5 and DEA 7, respectively, which seem to cause a delayed removal of transfused red blood cells not associated with haemolysis. For these reasons the first transfusion to a dog should not cause major problems. It should, however, be considered that when DEA 1.1-positive red blood cells are transfused for the first time to a DEA 1.1-negative subject, antibodies will be produced within 9 days and these antibodies will reduce the mean lifespan of the transfused red blood cells and could cause a delayed transfusion reaction. In the case in which the animal was previously sensitised (for example by a transfusion carried out “blindly”, without cross-matching the transfused blood), there will be a severe, acute haemolytic reaction. Transfusion reactions can be observed in all cases in which previously transfused individuals are transfused with red blood cells that are incompatible for all the other antigens besides DEA 1.1. These reactions can be observed within 4 days of the transfusion.
Transfusion reactions are not reported frequently (3%-13%). The low frequency of clinically significant natural antibodies, the fact that it is fairly rare for a dog to receive a second transfusion and, more probably, the low rate of notification of these episodes can explain this.
There are different opinions concerning the definition of the universal canine donor. According to the most restrictive definition, the ideal universal canine donor should be negative for DEA 1.1, 1.2, DEA 3, DEA 5 and DEA 7 and positive for DEA 4 (it is difficult to find DEA 4-negative subjects given that only 2% of the canine population have this characteristic). Other authors also accept DEA 7-positive dogs. In practice, the ideal situation would be to have only DEA 1.1-negative donor dogs. In the case that a DEA 1.1-positive dog is used as a donor, its blood must only be transfused to a DEA 1.1-positive dog to avoid sensitisation of the recipient towards the DEA 1.1 antigen.
In general, it is considered that typing for at least the DEA 1.1 antigen is indispensable prior to giving a transfusion of blood or blood derivatives. For dogs that have already received a transfusion, the blood group typing must be combined with a cross-matching test.
BLOOD GROUP TYPING
Blood group typing is usually based on serological studies involving agglutination reactions.
Since the DEA 1.1 blood group is associated with the production of antibodies and possible severe transfusion reactions in sensitised dogs and since about 50% of dogs are DEA 1.1-positive, typing for this antigen is definitely recommended prior to a transfusion. Typing the other blood groups is difficult because of the limited availability of the reagents needed to carry out the investigations and the difficulty in interpreting the results of the agglutination tests.
The methods that can be used to type the DEA 1.1 group include kits involving rapid agglutination on card (Fig. 1), agglutination in test-tubes and agglutination in columns of gel (Fig. 2). The typing is carried out on samples of whole blood collected into K3EDTA.
Particular care must be taken in the presence of agglutination. In these cases, the red blood cells from the dog to be typed must be washed three times in physiological saline. If the red blood cells remain clumped it will not be possible to type the blood group. In these cases if the patient must receive a transfusion, a DEA 1.1-negative donor dog must be found.
Suggested readings
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- Day HJ, Mackin A, Littelwood JD Ematologia e medicina trasfusionale del cane e del gatto. Ed. UTET, 271-316, 2004
- Giger U, Blais MC, Atti del 23° Congresso ACVIM di Baltimora, 2005
- Hohenhaus AE, Importance of blood groups and blood group antibodies in companion animals. Transf. Med. Rev., 18, 117-126, 2004
- Kessler RJ, Reese J, Chang D, Seth M, Hale AS, Giger U. Dog erythrocyte antigens 1.1, 1.2, 3, 4, 7 and Dal blood typing and cross-matching by gel column technique. Vet. Clin. Path., 39, 306-316, 2010
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- Weiss DJ, Wardrop J Schalm’s Veterinary Hematology 6th edition. Ed. Wiley-Blackwell, 711-756, 2010.