Neonatal Isoerythrolysis in Horse
and Mule Foals |
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Introduction
Tests for diagnosis of or potential for developing conditions due to antibody
mediated destruction of red blood cells (erythrocytes) in horses are of
three types. The first is used to determine the blood type of a horse;
the second is used to determine whether anti-erythrocyte antibody is present
in serum or colostrum; and the third is used to determine if antibody
is attached to the red blood cells (Coombs' test). The results of blood
typing, antierythrocyte antibody and Coombs' testing in horses provides
information useful in the diagnosis, management or prevention of antibody-associated
adverse reactions on red blood cells. Antibodies to red blood cells (often
referred to as antierythrocyte antibodies) can be transferred to another
horse through either colostrum (as from dam to foal) or through transfusion,
or they may develop to a horse's own red blood cells. When antierythrocyte
antibodies are transferred from a mare to its foal, a syndrome called
neonatal isoerythrolysis (NI) may develop. Antierythrocyte antibodies
transferred through transfusion may cause several types of adverse reactions,
called transfusion reactions. When a horse develops antibodies to its
own erythrocytes autoimmune hemolytic anemia (AIHA) may occur. Neonatal Isoerythrolysis (NI) in Horse
Foals
Neonatal isoerythrolysis is a disease of newborn horse foals and mule
foals that occurs within the first week of life. (See below for information
on the condition in newborn mules.) It is caused when the mare produces
antibodies against the foal's red blood cells and transfers those antibodies
to the foal through colostrum during the early stages of lactation and
nursing. This syndrome may occur when the blood type of the mare is different
than that of the stallion and the foal inherits the sensitizing red blood
cell type from the stallion. Mares that are negative for red blood cell
factors have the potential to develop antibodies against those factors.
Mares only become sensitized as a result of exposure to blood of a fetus
with incompatible blood type as a result of placentitis, difficult parturition,
or from exposure to blood containing the foreign blood factors from a
previous blood transfusion. Horses have 8 different blood
group systems, each of which has different factors. Some of the factors
are more commonly associated with NI (e.g. factors Aa, Qa and Qb). There
are several other, but less common, factors (Ua, Ka, Qc, Pa, Pb, Ac, Ab) that
can also cause NI. However, for unknown reasons, only a small number of
mares that are negative for a factor develop these antibodies. Generally,
a mare does not develop sufficient amount of antibodies to cause NI in
its foal during the first pregnancy from breeding to a stallion that has
a factor for which the mare is negative. However, in rare cases a mare
may produce sufficient antibody during a first pregnancy and can cause
NI in her foal. Increased risk of developing NI occurs with subsequent
pregnancies due to breeding to that stallion or another stallion with
the same red blood cell factor. After ingestion of colostrum containing
antibodies to red cell factors, the antibodies are absorbed into the foal's
blood. This is unlike the situation in humans where the antibodies (which
most frequently are anti-Rh antibodies) cross the placenta during late
pregnancy. The antibodies attach to the factors (antigens) on the foal's
red blood cells, and through a series of reactions, cause the foal's red
blood cells to rupture (erythrocyte lysis, which describes the syndrome's
medical name, neonatal isoerythrolysis). Neonatal
Isoerythrolysis (NI) in Newborn Mules
Neonatal isoerythrolysis is not a common condition in horse foals, although,
when it does occur, it is a severe, life threatening condition. In contrast,
the reported incidence of NI in newborn mules is about 10%, which is much
higher than the incidence in horses. In many mule pregnancies, the mare
develop antierythrocyte antibodies. It is probable that this occurs because
there are many differences in blood group factors between horses and donkeys.
In mules and donkeys the specific red blood cell factors have not been
identified, therefore blood typing is not available. It is likely with
every donkey/horse breeding that there is the potential for NI. Mules
suffering from NI frequently manifest thrombocytopenia (low platelet count)
as well as anemia, presumably because of the presence of anti-platelet
antibody as well as anti-red cell antibody. Alloimmune thrombocytopenia
(platelet destruction due to anti-platelet antibody) may occur without
NI as well. Determining the Potential
for Developing NI
A mare that has produced a foal that developed NI is likely to produce
others. The risk of producing another NI foal is greater if the mare is
bred to the same stallion or a stallion with the same inciting blood type
as that of the original stallion. Mares that have previously produced
a NI foal are excellent candidates for antierythrocyte antibody screening
in subsequent pregnancies. Mares that are either factor Aa, Qa, Qb, or
Ua negative, are also good candidates for antibody screening. In addition,
mares bred to a donkey are at risk of producing a NI newborn, and they
are also excellent candidates for antierythrocyte antibody screening.
Prevention of NI
There are two ways to prevent NI. One method is to withhold colostrum
from the foal of a mare that has antibodies to red cell factors of her
foal. The foal should be muzzled and the mare's milk emptied for 24-48
hours under the advisement of a veterinarian. An alternate source of colostrum
should be administered to the foal. The other method is to breed mares
only to stallions that have red cell factors that she also has or have
red cell factors to which she is unlikely to develop antibodies. Certainly,
if the mare is already pregnant, only the first method is feasible. In
this situation, the mare's serum should be tested for antierythrocyte
antibodies 2 to 3 weeks before she is scheduled to foal. The results of
this testing provides information that can used to predict the possibility
that a foal will develop NI. The antibody screen tests for antibodies
to 31 red cell factors. Antierythrocyte antibody testing is performed
using a panel of red blood cells from 11 horses and one donkey. In addition,
if the stallion or jack's red blood cells are available, crossmatching
with the mare's serum is also performed at no extra charge. Blood typing of the mare and potential stallions can provide information that is useful for preventing NI. For mares that have had a foal that developed NI, this information can be used to select a sire that is negative for the blood group factor to which she has antibodies. Currently, the following blood factors are determined. A (a,b,c,f,g), Ca, D (a,g,k), Ka, P (a,b), Q (a,b,c), Ua, V and W.
Diagnosis of NI
Clinical signs of red blood cell lysis in the affected foal usually occur
within 6-72 hours after birth. The major clinical signs are lethargy,
elevated pulse (heart rate), increased respiratory rate, anemia and jaundice.
If mild, the foal may recover without treatment, however the disease may
progress to severe anemia and organ dysfunction leading to death. Diagnosis is confirmed by demonstrating antibody on the surface of the foal's red cells by performing a Coombs' test (EDTA sample). Diagnosis is supported by demonstrating anti-red cell antibodies in the colostrum or serum of the mare. Samples
for testing
For NI antibody screen of the mare, 2-3 ml of serum is required. Allow the
blood from a 10 ml red top tube to clot for 30 minutes, spin and separate
the serum into another tube. If the mare has had a previous NI foal, please
send a whole blood (EDTA) tube as well.
Samples from outside the USA: Contact the hematology laboratory to receive a copy of the import permit or download permit here.
Submission Form Request a form to be faxed or mailed to youReporting of Results Generally testing is performed within a few days of receiving the sample. Results will be transmitted through FAX or phoned. |