Neonatal isoerythrolysis (NI), also known as hemolytic icterus or hemolytic anemia, is a disease most commonly seen in kittens and foals, but has also been reported in puppies. It occurs when the mother has antibodies against the blood type of the newborn.
Neonatal isoerythrolysis in kittens In cats, the antibodies are already present in the mother's blood before parturition. The blood group antigens are similar in structure to the antigen of a common bacteria in the gut of cats leading to antibody formation. Kittens obtain the majority of their immune response from the colostrum, and are not born with a strong immune response. When they absorb the mother's antibodies against their blood type it causes lysis of the red blood cells leading to anemia. Symptoms include lethargy, weakness, depression, pale mucous membranes, fever, and blood in the urine. Hypoxia may lead to forebrain disease, increased heart rate and respiratory rate, and liver or kidney disease. Animals suffering from this disease must be taken to a veterinarian immediately. Treatment includes fluid support and blood transfusions. The condition is most commonly seen in kittens with type-A blood born to mothers with type-B blood since type-B cats form very strong anti-type A antibodies. The condition is less common (and less severe) in type-B kittens born to type-A mothers. It can be prevented by blood typing the mother and kittens. If there is a blood-type mismatch, the kittens should not be allowed to nurse for 72 hours from the mother to prevent the passage of antibodies in the colostrum. After that, the kittens can be allowed to nurse naturally.
Neonatal isoerythrolysis in foals Neonatal isoerythrolysis usually presents during the first 4 days of a foal's life, or 4-7 days in mule foals. It is a medical emergency and requires immediate veterinary attention to prevent further decline in health and subsequent death.
Pathophysiology Neonatal isoerythrolysis occurs if a foal is born with a blood group that is different from its dam, and then receives antibodies against those red blood cells (alloantibodies) through the mare's colostrum, leading to the lysis of the foal's red blood cells. There are thus three requirements for this disease to occur:
The foal must inherit and express an antigen from the stallion's blood group that is not present in the mare. The mare must have already produced alloantibodies against this antigen, which can only occur if she has been previously exposed to the incompatible red blood cells prior to birth of the foal. The foal must ingest these alloantibodies through the colostrum of the mare when the gut is still "open" (able to absorb antibodies, the first 24 hours following birth). The first scenario for the mare's exposure occurs if she is bred to a stallion of incompatible blood group, and during foaling receives the foal's red blood cells into her circulation due to transplacental hemorrhage. Because of the delay in production of antibody, this first foal is not at risk for isoerythrolysis since the mare will not have circulating antibodies until after colostrum production has ceased, meaning this foal will never have a chance for exposure. However, subsequent foals that are by the same stallion or a different stallion that carries the same incompatible blood group, are at risk, and as such this disease is most commonly seen in foals out of multiparous mares. Additionally, exposure can occur due to placental abnormalities in early gestation that allow the foal's red blood cells to leak into the mare's circulation, or if the mare is exposed through blood transfusion. Because this exposure occurs well before the foal receives colostrum, the mare will have circulating antibodies at the time of parturition and therefore the foal is at risk of developing NI. During the final month of gestation, alloantibodies concentrate into the colostrum. Horses, unlike humans, have an epitheliochorial placenta which prevents the transfer of antibodies to the foal in-utero. Foals are only exposed when they first nurse and ingest colostrum, so therefore are born without the disease and acquire it soon after birth. After ingestion, these antibodies coat the red blood cells of the foal, leading to lysis through the complement system or removal by the mononuclear phagocyte system, and causing subsequent anemia.
Blood groups associated with neonatal isoerythrolysis Most blood groups do not produce a highly immunologic response when the mare is exposed from previous foals or through placental leakage of red blood cells. However, a few factors, such as Aa and Qa, do lead to a significant response and therefore account for the majority of cases of isoerythrolysis. Mares that are Aa- and Qa-negative are therefore most likely to produce a foal with this condition. This is most commonly seen in Thoroughbreds (19%) and Arabians. Additionally, mule foals are especially at risk due to an associated donkey factor. Immune mediated thrombocytopenia often occurs concurrently in mule foals suffering from neonatal isoerythrolysis. Some mares have natural alloantibodies, usually to the Ca blood group, without ever having a known exposure to that blood group. This is seen in 10% of Thoroughbred mares and 20% of Standardbred mares. In this case, Ca alloantibodies are thought to actually suppress a response against Aa blood groups, and therefore these mares do not make Aa alloantibodies if the foal has both Ca positive and Aa positive blood. These natural alloantibodies have not been shown to produce isoerythrolysis in foals, and are actually thought to help prevent NI by desensitization of the immune system and preventing the more harmful Aa alloantibodies from forming. Alloantibodies against De, Ua, Pa, and Ab blood groups have also been associated with neonatal isoerythrolysis.
Clinical signs and testing
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