1. Bitches with erythrocytes lacking the canine A factor were immunized with intravenous injections of A-positive dog cells and mated with A-positive sires. ll A-positive pups born to such dams developed hemolytic disease provided they suckled the immunized dam during the first day of life. There was no evidence of transplacental isoimmunization or of transfer of antibody across the placenta from mother to pup. Anti-A could not be demonstrated in the blood of pups at birth and was not acquired by pups that first suckled an immunized bitch after the first day of life. A-positive pups born to a non-immunized bitch developed hemolytic disease after suckling an immunized foster dam on the day of birth.

2. Of 24 affected A-positive pups, 3 were sacrificed, 9 died within three days of birth and 12 recovered, 2 with the aid of transfusions of A-negative blood. Autopsies revealed varying degrees of hepatomegaly, splenomegaly, erythroid hyperplasia of the bone marrow, extra-medullary erythropoiesis, and questionable evidence of specific injury of the nerve cells of the basal nuclei of the brain.

3. The degree of anemia in the A-positive pups varied widely, the minimum hematocrit for the group being 10 per cent at forty-eight hours after birth. Erythroblastosis, reticulocytosis and spherocytosis were noted in most of the severely affected pups and osmotic fragility of the red cells was substantially increased in all of the A-positive pups exposed to anti-A.

4. The concentration of bilirubin in the serum of most of the affected pups was only slightly increased. The relatively small increases in serum bilirubin, compared with those in hemolytic disease of human infants, are presumably attributable to the unusual capacity of the dog liver for excreting bilirubin.

5. The red cells of all affected A-positive pups gave antiglobulin (Coombs) reactions and in surviving pups the cells were agglutinable in antiglobulin rabbit serum for as long as twenty-two days in A pups and sixty-five days in A’ pups. The degree of reactivity with antiglobulin serum was not correlated with the severity of the hemolytic process. Erythrocytes of the very mildly affected A’ pups were strongly agglutinated by antiglobulin serum but showed no definite sphering and only slight increase in osmotic fragility.

6. Serum of the 20 A-negative litter mates examined in this study contained anti-A for periods as long as thirty-two days while the red cells of these pups remained normal. A few of the A-positive pups also had anti-A in the serum. The in vitro behavior of anti-A in the pups’ sera was identical with that of anti-A in the maternal sera.

7. Twelve C-positive pups in 2 litters born to bitches immunized against the canine C factor showed no evidence of hemolytic disease.

8. Hemolytic disease of newborn dogs is compared with that of human infants and the need for further investigation of certain aspects of the disorder in both species is stressed.

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