Miscellaneous conditions of equine neonates (Proceedings)

New information on neonatal isoerythrolysis, kernicterus, neutropenia, thrombocytopenia, hypoxic ischemic encephalopathy will be discussed

Neonatal isoerythrolysis (ni)

Neonatal isoerythrolysis occurs when the foal inherits blood antigens (types) from the stallion that are different from that of the mare. As a result, the mare may produce antibodies to these antigens, which are then concentrated in her colostrum. It is thought that repeated exposure to red cell antigens after numerous foalings or placental leakage of blood sensitizes the mare. There have also been reports of primiparous mares also having NI foals. The foal nurses the colostrum, and, depending on the concentration and type of antibodies, the foal develops hemolytic anemia within 1-7 days of age. Red cell types Q and A are the most lethal antibodies. Occasionally, the types U, S, T, and, more rarely, other antibodies can induce NI. Many mares have anti-C type antibodies, which do not induce NI. Mule foals inherit "Donkey factor" from the Jack, and are at a greater risk of NI and immune mediated thrombocytopenia.

Clinical signs

Depend on the rapidity of onset of anemia.

     1. Weak but still desires to nurse

     2. Tachypnea and tachycardia

     3. Pallor of mucus membranes if acute

     4. Icteric if chronic (kernicterus or bilirubin encephalopathy has been reported in the foal)

     5. Reddish urine

Laboratory diagnosis

Other than a PCV, laboratory diagnosis is not necessary in most cases

     1. PCV<20; hemoglobinuria

     2. Direct Coombs test (usually not necessary), false positives common. Flow cytometry can be used for definitive diagnosis (Kansas State or Cornell)

     3. Demonstration of anti-red cell antibodies in the sera or colostrum of the dam.

Treatment

     1. Usually too late to withhold colostrum when the diagnosis is made.

     2. Replacement of RBCs (Usually done when PCV drops below 15-20% but this depends upon the rapidity of the drop in PCV)

     3. Blood (packed RBCs are preferred) from an Aa, Qa negative donor. The ideal donor is the dam, but her red cells must be washed to remove plasma that contains the offending antibodies. Collect the dam's blood in ACD or NaCitrate and centrifuge or allow red cells to settle, remove plasma and resuspend in saline. Wash 2 more times, if possible, after red cells in saline settle out. This procedure takes several hours, but may be performed at the local red cross!

     4. If death looks imminent use blood from any horse (any horse that has not had a foal).

     5. Constant monitoring of the PCV is necessary after transfusion because transfused red blood cells live only 3 +/- days.3).

     6. Fluid therapy to prevent pigment-induced renal disease.

     7. Antibiotics

     8. FPT is rare in these foals. If it has occurred, transfuse with whole blood rather than packed red cells

Complications

Foals that have received >2 transfusions of blood are at a great risk of iron toxicity resulting in fatal liver failure. Excessive transfusions should be avoided as foals are unable to eliminate excess iron derived from hemolyzed red blood cells.

Prevention

     1. Some farms blood type all mares for identification of Aa and Qa negative mares (i.e., the mares at risk). At risk mares can be screened shortly before foaling (within 30 days) to detect alloantibodies in their plasma. (Serology Laboratory, UC, Davis, CA 916-752-2221, or Kentucky 606 257-3022).

      2. Mares with a history of an NI foal can be bred to stallions that are negative for the red cell factor that is involved (then the foal will not have the red cell antigens which alloantibodies attack). The mare's udder should be stripped preemptively prior to foaling and for 24 hours after foaling. The colostrum should be discarded.

     3. Foalings of NI mares can be attended to prevent nursing of the dam's colostrum (in these cases banked colostrum or plasma transfusion (2 liters) is used to prevent FPT).

      4. Routine screening of colostrum with foal blood (i.e. Jaundiced foal agglutination test) before foals are allowed to nurse, especially for at risk mares.

Kernicterus

In rare cases severely anemic foals suffering from NI will have markedly elevated bilirubin concentrations. This can cause cerebral toxicity and seizures. Transfusions should be avoided unless absolutely necessary. Phenobarbital may help induce hepatic enzymes. Ultraviolet light lamps are used for human infants, but foals would require shaving, which would likely be too stressful.

Immune mediate thrombocytopenia

Similar to NI, occasionally alloantigens can attack the foal's platelets.1 These foals present with identical clinical signs as NI foals, with the addition of petechial hemorrhages. The platelet counts are also low on the CBC. Treat identical to NI foals.

Immune mediated neutropenia

Similar to NI, occasionally alloantigens can attack the foal's neutrophils. 23 These foals are usually bright and alert, but with severe neutropenia which usually resolves after 2-3 weeks. Antibodies on neutropils can be confirmed by using Flow cytometry. Contact Melinda Wilkerson at Kansas State 785-532-4818 www.vet.ksu.edu/depts/dmp/service/immunology/index.htm.

Sepsis must be ruled out, and regardless, intensive antibiotic therapy is indicated due to the low neutrophil numbers. Isolation and attention to hygine is also very beneficial. Some people have advocated the use of granulocyte colony stimulating factor (G-CSF) subcutaneously. Neupogen® 300 µg vial is ~$300. This will cause release of neutrophils from the bone marrow.

Ulcerative dermatitis, thrombocytopenia, and neutropenia

Sporadic cases of transient ulcerative dermatitis, severe thrombocytopenia, and mild neutropenia were recently reported in 6 foals.3 The foals presented at < 4 days of age with oral and lingual ulcers, and crusting and erythema around the eyes, muzzle, and perineal, inguinal, axillary, trunk, and neck regions. These foals had severe thrombocytopenia, leukopenia, and mild neutropenia. Most foals had petechiae and ecchymotic hemorrhages and 50% had bleeding tendencies. Histopathology of the skin showed subepidermal clefting with subjacent vascular dilation, dermal hemorrhage, and superficial papillary necrosis. Foals should be given supportive treatment with broad-spectrum antibiotics, possibly corticosteroids, and whole-blood transfusion or platelet-rich plasma if required. All foals reported by Perkins survived and were healthy as yearlings. Two mares each produced two affected foals, but upon subsequent pregnancies to different stallions, they both had healthy foals when an alternate source of colostrum was given. It is suspected that there is a possible relationship between colostral antibodies or some other factor in the colostrum and the thrombocytopenia and skin lesions.

Perinatal asphyxia syndrome (pas)

Synonyms for PAS include neonatal maladjustment syndrome, dummy, wanderer, and Hypoxic-ischemic encephalopathy (HIE). PAS refers to noninfectious CNS disease in foals < 4 days of age, excluding congenital and genetic defects or trauma involving the CNS. It is postulated that neuronal hypoxia caused by placental disease, premature placental separation, maternal illness, dystocia, caesarean section, birth trauma or airway obstruction may lead to PAS. However, in most cases no risk factors are identified.

Clinical signs

Foals may be born with clinical signs or develop them within the first 3 days of life. Cerebral dysfunction results in behavioral abnormalities, including a lack of interest in the mare, restlessness, hyper-responsiveness to handling, abnormal posture, tongue protrusion, obsessive licking, abnormal jaw and facial movements, star-gazing, head-pressing and abnormal vocalization. Seizures ranging from mild abnormal movements of the face and jaw to generalized seizures with recumbency and paddling of the limbs are not uncommon. There may also be head tilt, facial paralysis, lethargy, stupor or abnormal breathing patterns. The initial hypoxic event may also have caused ischemic damage to other organs such as kidney, gastrointestinal tract and liver, resulting in azotemia, diarrhea and elevated activities of liver enzymes.

Diagnosis

Diagnosis of HIE is based on rule out of other abnormalities and often complete resolution. Foals may have HIE in addition to sepsis, but uncomplicated cases of HIE have a normal CBC and serum chemistry unless complicated by organ dysfunction. Cerebrospinal fluid may be normal or xanthochromic, with an increased concentration of red blood cells and protein. CNS necrosis, edema, and hemorrhage are characteristic postmortem findings.

Treatment

Treatment is generally supportive with control of seizures, prevention (or treatment) of sepsis, and pharmacological treatment of possible CNS edema and hemorrhage. Foals should receive broad-spectrum antimicrobial coverage and ensure adequate maintenance of hydration and nutrition. Most foals require feeding by indwelling nasogastric tube (initially 10% of the body weight in milk divided into 12-24 feedings per day). If feeding is well tolerated, the amount can be slowly increased to 15, then 20 % of the foal's body weight. As the foal becomes stronger and clinical signs begin to resolve, training to reestablish nursing from the mare should be initiated. Seizures should be controlled with diazepam. If unsuccessful or recurrent, phenobarbital should be given for > 7 days. A CRI of midazolam can be effective when there is no response to phenobarbital. The use of anti-inflammatory or antiedema drugs is controversial. The following may be used: flunixin meglumine, MgSO4 CRI, thiamine, DMSO, vitamin E, vitamin C, mannitol or hypertonic saline. Corticosteroids should not be used.

Differential diagnoses

Differential diagnoses include brain trauma; birth defects (hydranencephaly, hydrocephalus, lavender foal syndrome); infectious causes (bacterial meningitis, equine herpesvirus 1); metabolic causes (hypoglycemia, hypoxemia, electrolyte or acid-base derangement, kernicterus, hepatoencephalopathy) and non-neurologic causes, including severe sepsis, branching enzyme deficiency, and white muscle disease).

Prognosis

90% of uncomplicated HIE cases resolve within several days with supportive care.

Drugs, Dosages and Indications for possible treatments for PAS

Summary

Neonatal isoerythrolysis, thrombocytopenia and neutropenia are caused by ingestion of incompatible colostrum. The most common causes of neurologic disease in neonatal foals is PAS. Differentials include include brain trauma and meningitis. Treatment of neonatal isoerythrolysis, kernicterus, neutropenia, thrombocytopenia, hypoxic ischemic encephalopathy all require supportive care and prophylactic antmicrobial therapy because of the increased risk of sepsis.