Canine blood-typing
Canine blood-typing Andy Pachikerl, Ph.D Introduction: Dog erythrocyte antigens are responsible for initiating approximately 70% to 80% of immune-mediated transfusion reactions in the dog. As with other species, the red blood cell antigens found in the dog have various immunogenicities. In health, these antigens are participants in cell recognition-self versus nonself. In disease, they may serve as antigens for antibody or markers in disease occurrence. Little is known about their biochemical properties. Currently their description is reliant on polyclonal antibody serology. This reliance has limited the progress of transfusion practice in the dog. Historically, the study of canine blood groups and their importance in transfusion began in the 1600s through a physician, Richard Lower. He is credited with the first canine-to-canine transfusion. The efforts of doctors Lower and Denis in heterologous transfusion using lamb, dog, and human subjects introduced the basic transfusion premise “like transfuses like.” In 1910, Von Dungem and Hirszfeld documented the presence of four hemolysins and agglutinins based on canine alloimmunization (Swisher & Young, 1961). Further work by Ottenburg, Kaliski, and Friedman in 1913 confirmed these findings. From 1937 to 1949, Wright, Whipple, and Eyquem further defined the presence of six canine blood groups (Colling & Saison, 1980). However, not until 1961 was the importance of these antigens in transfusion and disease investigated by Swisher, Young, and Trabold (Swisher, et al., 1962). To date, the work submitted by Swisher and Young remains the most current published information of the importance of canine blood groups in transfusion (Swisher, 1954; Swisher, et al., 1962; Young, et al., 1951). Additional blood groups have been identified by Rubenstein (1968), Suzuki/5 Colling and Saison (Colling & Saison, 1980; Colling & Saison, 1980), and Symons and BelLl9 (Symons & Bell, 1992). Of this latter group, only the antigen first noted by Rubenstein (Colling & Saison, 1980) was evaluated in regard to transfusion significance by Bull (Bull, 1976). The importance of canine blood groups in veterinary transfusion medicine is based on three factors: the incidence of the antigen in the dog population, the incidence of naturally occurring antibody within the population, and the effect of the antibody against the antigen in vivo. Current blood typing schemes identify six erythrocyte antigens with possible importance. The dog erythrocyte system Blood groups are defined by glycolipids and glycoproteins on the surface of the red blood cell membrane. Current blood typing schemes identify six dog erythrocyte antigens (DEAs): 1.1, 1.2, 3, 4, 5, and 7 (Table 1). Blood groups are independently inherited. Simple Mendelian laws of dominance govern their inheritance. These antigens are defined by using polyclonal antibodies generated through canine alloimmunization. Polyclonal antibody recognition may be dependent on multiple recognition sites to define the “antigens” currently accepted. Biochemically, little is known about the DEA system. Table 1. Dog erythrocyte antigens established as international standards: classification, occurrence, and significance This blood group system has been defined with multiple alleles. They include the antigens 1.1, 1.2, 1.3, and a null type. An individual dog may show only one of the four phenotypes. Family studies suggest a Mendelian type of autosomal dominance. Table 2 describes the current phenotypic and genotypic information on this blood group system. 1.1- and 1.2-positive dogs have been studied for transfusion significance. Naturally occurring antibody to these alleles has not yet been found. Therefore, first-time transfusion reactions do not occur. However, if a negative dog is exposed to 1.1- positive erythrocytes, a strong hemolysin can result. On second exposure, an immune-mediated hemolytic transfusion reaction results causing removal of transfused cells in less than 12 hours. Hemoglobinuria and hyperbilirubinemia frequently occur. In addition to uncross matched, untyped transfusion, pregnancy can cause production of antibody against DEA 1.1 25% of the time. For these reasons 1.1-positive dogs are excluded as transfusion donors. 1.2-positive dogs can cause a problem as both the transfusion donor and recipient. A previously sensitized negative type dog undergoes permanent red blood cell removal and loss 12 to 24 hours after the administration of 1.2-positive red blood cells. Thus, 1.2-positive dogs are poor erythrocyte donors. If a 1.2-positive dog is sensitized with DEA 1.1 red blood cells, it will produce a potent anti-DEA 1.1 antibody. Administration of DEA 1.1 red blood cells to a sensitized 1.2 dog results in an immediate hemolytic transfusion reaction. Therefore, 1.2-positive dogs are at risk after sensitization for immediate transfusion. 1.3-positive dogs have not been evaluated for transfusion significance. Future study is limited because of the unavailability of typing sera for DEA 1.3. DEA 7 This red blood cell antigen is the most controversial among the six antigens discussed. Published reports of naturally occurring antibody to this antigen suggest that this antibody has a natural prevalence as high as 50% in DEA 7-negative dogs. Recent reports by Giger fail to support the presence of naturally occurring anti-DEA 7. Observations by the author suggest that naturally occurring antibody does exist in 20% to 50% of all DEA 7-negative dogs. However, the naturally occurring antibody is quite weak, rarely producing a titter greater than 1:8. In the presence of naturally occurring antibody, as in the cat, immunemediated transfusion reaction can occur during a first transfusion. Sensitized DEA 7-negative dogs, when transfused with DEA 7-positive erythrocytes show a delayed transfusion reaction. Hemolysis does not occur; however, an irreversible sequestration and loss of red blood cells occurs in 72 hours. This type of delayed transfusion reaction is only significant if the regenerative ability of the transfusion recipient is compromised. Because of the presence of naturally occurring antibody in the DEA 7-negative population and because of the delayed loss of erythrocytes in sensitized dogs, DEA 7-positive dogs are not recommended as donors. DEA3 This antigen has not been considered significant because of its low incidence in the dog population of the United States. However, recent evaluation of DEA type by breed suggests that it may be more important. Only 6% of the general population has DEA 3-positive cells. Yet 23% of the Greyhounds typed from 1990 to