Neonatal lsoerythrolysis: A Complex, Yet Preventable Disease

Neonatal isoerythrolysis (NI) is an uncommon, complex disorder of newborn foals that results from a blood group incompatibility that exists between the dam and the foal. NI occurs after the foal suckles and absorbs antibodies from the mare's colostrum, which then attack the foal's red blood cells. This results in destruction of the red blood cells of the foal and subsequent anemia (decrease in red blood cells).

Red blood cells (also known as erythrocytes) are crucial in the maintenance of life. Erythrocytes circulate throughout the body in blood vessels, picking up oxygen in the lungs and transporting it to all of the cells within the body. Hemoglobin is a protein within the red blood cell that actually carries the oxygen molecule. When red blood cells are destroyed, hemoglobin and other substances within the cell are released into the blood stream and the cell can no longer function properly in its ability to distribute oxygen. The lack of oxygen-carrying ability and the presence of hemoglobin in the blood that ensues can then lead to a number of disease conditions.

The surface of the red blood cell is covered with a number of structures called antigens. These structures provide a 'fingerprint' for the cell, giving the cell an identity and enabling the body to recognize the cell. When one is exposed to blood that is different from their own, problems can arise. If this new blood has antigens on it that the body does not recognize, antibodies will be produced in an effort to destroy the new red blood cells, which are perceived as invading organisms. This is a normal defense mechanism that the body utilizes to protect itself from disease and infection.

The antigens on the red cells are inherited from both parents and are generally a combination of the two. These antigens are given specific names (usually letters) depending on their structure, and are then placed in various groups. This is the basis for blood grouping. Humans have four blood groups (A, B, AB and 0). Horses, however, have eight blood groups and anywhere from one to eight different types of antigens within a given group.

 

Note: The capitalized letter refers to the blood group while the lower case letter refers to specific antigens within that blood group. The Aa and Qa types that are implicated in NI are bolded.

Only a small percentage (1-2%) of mares are at risk to produce foals that develop neonatal isoerythrolysis. These include mares that lack the Aa and Qa antigens on their red blood cells. Thoroughbreds and Standardbreds are at a higher risk than other breeds. Also, this disease is more commonly seen in multiparous mares, which will be explained shortly.

NI requires a series of events to occur, in a specific order, before the disease results. First, a mare that is Aa or Qa negative (lacks the antigen) must be bred to a stallion that is Aa or Qa positive (has the antigen). The fetus will then inherit antigens from both parents. If the fetus inherits the Aa or Qa antigen from the stallion, it will possess a blood group that is different from its mother. If the mare is exposed to her fetus' blood (which can occur during late pregnancy or during parturition), she will produce antibodies directed against the Aa or Qa blood type. This is not a problem during the first exposure, because the mare does not have sufficient time to produce antibodies. However, in successive pregnancies, problems can arise. The mare has been creating antibodies against Aa and Qa blood and then accumulates them in her colostrum during later pregnancies. Any later foal that is born Aa or Qa positive is now at risk. When it drinks the dam's colostrum, the antibodies are absorbed into the bloodstream from its digestive tract, which then attack and destroy the foal's red blood cells. It is for the reasons above that the disease is seen only after the foal suckles and usually only in multiparous mares.

The signs that you see are due to the destruction of red blood cells (hemolytic anemia). They include progressive weakness, lethargy, an increased breathing rate, an increased heart rate, repeated 'yawning', a yellowish discoloration of the membranes, seizures and possibly death. The foal will generally be normal at birth and signs will only be observed after the foal has suckled from the mare. This can vary from 8-96 hours post-suckle.

Your veterinarian can generally diagnose neonatal isoerythrolysis based on the clinical signs. However, several tests are available that utilize the blood from the main and foal or the mare's colostrum.

When a foal has NI, your veterinarian will provide supportive therapy for the foal. A blood transfusion may be required to provide red blood cells, until the foal can produce more on its own. The foal may require fluids, nutritional support, antibiotics and steroids. The foal should be kept in a warm dry environment that is free from stress and activity should be limited until recovery is complete.

NI is a completely preventable disorder. If your mare has lost one or more foals shortly after birth, you should be concerned about NI. Her blood can be tested to determine her blood type and if she is in a higher risk group (Aa or Qa negative). If you have an at-risk mare, there are several ways to prevent the occurrence of NI in later pregnancies. These include:

McClure JJ. Strategies for prevention of neonatal isoerythrolysis in horses and mules. Equine Vet Educ 1997:9(3):118-122.

McClure JJ. How should a mare whose foal died from neonatal isoerythrolysis be managed in subsequent pregnancies? Compend Contin Educ Pract Vet, 1999: 21(2):169-175.

Smith B. Neonatal Isoerythrolysis. Smith's Large Animal Internal Medicine, Mosby 1996:1865-1873.

Whiting JL, David JB. Neonatal Isoerythrolysis. Compend Contin Educ Pract Vet, 2000:22(10):968-975