Alloimmune neonatal neutropenia and neonatal isoerythrolysis in a Thoroughbred colt.

A 3-day-old Thoroughbred colt was originally presented for treatment of neonatal isoerythrolysis, which was treated with a blood transfusion. However, persistent neutropenia was observed despite the absence of detectable infection. Subsequently, a granulocyte agglutination test was performed by incubating the colt's neutrophils with the mare's serum; results were positive, leading to a clinical diagnosis of alloimmune neonatal neutropenia. The diagnosis was further supported via flow cytometric analysis. The colt was hospitalized and treated prophylactically with antimicrobials and 4 separate doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 1.4-3.5 µg/kg, subcutaneously) in attempts to maintain the neutrophil count within reference intervals over a 4-week period. The colt's neutrophil count increased after administration of rhG-CSF and eventually stabilized within reference intervals by day 20. The colt maintained normal neutrophil counts after discharge and was reportedly healthy at 6 months of age. Alloimmune neonatal neutropenia should be considered in foals with persistent neutropenia in the absence of infection. Alloimmune neonatal neutropenia can be treated with prophylactic antimicrobials combined with rhG-CSF with a favorable outcome.

[Isoimmune haemolytic icterus in neonatal calves as a consequence of vaccination against piroplasmosis]. / Isoimmunhämolytischer Ikterus bei Kälbern in Folge einer Piroplasmose-Schutzimpfung.

The article refers about several cases of isoimmunohaemolytic icterus in neonatal calves from different farms, whose dams had all been vaccinated against piroplasmosis. Clinical signs of immunomediated icterus neonatorum gravis, results of blood chemistry (with special regard to liver-specific parameters in the neonatal calf and results of haematology) as well as gross pathology and pathohistology are to be discussed. It is summarized, that the most relevant indicators for a hepatopathy in the newborn calf are total-bilirubin and the glutamate-dehydrogenase. Today, the production of piroplasmosis-vaccines out of blood of splenectomized animals is referred to as the only practicable method of harvesting sufficient amounts of vaccine-antigen.

Neonatal isoerythrolysis involving the Qc and Db antigens in a foal.

In 1992, a multiparous 13-year-old Thoroughbred mare and her 48-hour-old colt were examined because of possible neonatal isoerythrolysis (NI). Supportive treatment was administered, and the foal recovered without requiring a transfusion. According to the owners, the mare had delivered foals without incident during 1987 and 1991. The mare was barren during 1993, but in 1994, delivered a filly that developed severe NI. The foal was given 3 transfusions and eventually recovered without complications. Blood typing analysis of the mare and its foals indicated that all 4 foals were positive for the Qc, Db, and Dq antigens, and the 3 most recently born foals were positive for the Ua antigen; however, the marc was negative for the Qc, Db, Dq, and Ua antigens. The mare did not have alloantibodies against Ua and did not react to the Dq antigen. However, in 1994, the mare reacted against the Db (the reaction was characterized by strong agglutination and an increase in titer at the time of parturition and a subsequent decrease) and Qc (the reaction was characterized by weak lysis and an increase in titer at the time of parturition and a subsequent decrease) antigens. Results of testing in this mare and foals suggested that although approximately 90% of all cases of NI in horses are attributable to the Aa or Qa antigen, other antigens may be involved.

Suspected neonatal isoerythrolysis in two Baird's tapirs (Tapirus bairdii).

Two Baird's tapir (Tapirus bairdii) calves born at the Columbus Zoo from the same sire and dam developed hemolytic anemia that was consistent in history and clinical signs with neonatal isoerythrolysis (NI). One calf developed severe, fatal hemolytic anemia after being fed maternal colostrum, and the other developed moderate hemolytic anemia after being fed equine colostrum. No cross-reactivity was demonstrated between sire and dam blood samples, and both tapirs possessed serum antibodies reactive against equine blood group Ca and antigens reactive with several equine blood group D antibodies. Electrophoresis demonstrated significant genetic diversity between tapir and equine blood proteins. Agglutination testing demonstrated strong reactivity between a far greater percentage of equine colostrum samples when tested against sire and dam tapir blood (61% and 65%, respectively) than would be expected for equine blood (2%). These data are suggestive of a diagnosis of NI but are not definitive. Further study is required to determine whether NI occurs in tapirs and whether equine colostrum is harmful to tapir calves.

Feline colostrum--friend or foe: maternal antibodies in queens and kittens.

The transfer of immunoglobulins (Ig) by colostrum from the queen to the neonatal kitten not only provides protection from infection, but may also cause serious illness. Neonatal isoerythrolysis may occur when kittens of blood type A or AB receive colostral anti-A alloantibodies from a type B queen. In contrast to other species, Ig concentrations in milk and colostrum did not differ markedly. Gastrointestinal absorption of IgG was limited to the first day of life. The half-lifes of maternally derived IgG and IgA in kittens were shorter than in puppies. In conclusion, milk from another queen may be given as a replacement for colostrum to neonatal kittens. Kittens at risk of neonatal isoerythrolysis must be removed from their type B queen during the first day of life and may safely receive milk or colostrum from a type A queen.

Characterization of a red blood cell antigen in donkeys and mules associated with neonatal isoerythrolysis.

A red cell antigen of donkeys and mules was identified using antibodies in serum from a mare which produced a mule foal affected with neonatal isoerythrolysis (NI). Subsequently antibodies with similar activity were identified in the sera of other mares which had produced mule foals and were produced by immunization of horses with blood from donkeys. The antigen detected by these antibodies does not correspond to any recognized horse red cell alloantigen. This may be a xenoantigen since all donkeys (and mules) tested have shared this antigen and all horses tested have lacked the antigen. The results suggest that all mule pregnancies (donkey sire x horse dam) are incompatible with regard to this factor and a potential for neonatal isoerythrolysis exists in all cases.

[Neonatal isoerythrolysis in newborn foals]. / Die neonatale Isoerythrolyse bei neugeborenen Fohlen.

Aetiology, pathogenesis, clinical symptoms, diagnosis, prophylaxis and therapy of neonatal isoerythrolysis in foals are presented. Neonatal isoerythrolysis is caused by isoimmunisation of a brood mare to the Aa and Qa erythrocyte antigens of the foal. The disease can develop, when the mare does not possess Aa resp. Qa blood group antigens, is sensitized to the Aa or Qa erythrocyte antigens--i.e. through pregnancy, parturition, blood resp. plasma transfusions, etc.--and the foal suckles colostral antibodies to its own blood cells. Aa and Qa antibodies can cause haemagglutination and haemolysis in the foal, with a consequent decline in erythrocytes, PCV and haemoglobin resulting in several clinical symptoms. In most instances the first signs of the disease are noticed by day 2 and 3, ranging from 8 to 96 hours of life. Diagnosis is based upon clinical examination and determination of erythrocyte count, PCV and haemoglobin concentration and can be further confirmed by immunological tests. Several tests can be used to prevent the occurrence of neonatal isoerythrolysis in the newborn foal. Prior to parturition, brood mares can be typed for blood groups and tested for antibodies to Aa and Qa in order to identify mares at risk for causing neonatal isoerythrolysis in the foal. After birth, compatibility of the mare's colostrum and the foal's erythrocytes can be checked by the "jaundice foal agglutination" test. Some instructions for prophylaxis of neonatal isoerythrolysis and for the treatment by red blood cell resp. whole blood transfusions are given.

Presumptive neonatal isoerythrolysis in cats.

Entire or partial litters of 4 queens died due to hemolytic anemia within 1 to 2 days of birth. Necropsy and histologic examination of tissues from 6 dead kittens were indicative of neonatal isoerythrolysis. Blood samples from affected kittens were not available for study. Nevertheless, hemolysins and agglutinins in each queen's serum reacted with RBC from 2 sires of the affected litters. These antibodies, identified as anti-A, also reacted with the RBC from 64 random-source cats.

Hematology, blood typing, and immunology of the neonatal foal.

Hematologic parameters change during the first 10 days of life. Erythrocytes increase in number but decrease in size and hemoglobin concentration. The PCV, hemoglobin, and platelet count also decrease. Total blood and plasma volume and, to lesser extent, erythrocyte volume decrease. Normal neonatal foals may have immature neutrophils (up to 5 per cent bands), and their early rapid rise in neutrophil numbers may be accompanied by a lymphopenia. Monocytes, eosinophils, and basophils are all absent or low initially. Infectious processes can cause rapid and variable changes in the leukogram. However, elevation of fibrinogen levels may lag behind the development of an inflammatory process, and this parameter should not be relied on for early evidence of infection. After 12 hours of life, there is generally a decrease in serum concentrations of Na, Cl, iron, creatinine, BUN, plasma protein, and possibly calcium. LDH, SAP, P, bilirubin, and glucose concentrations are all higher in foals than in mature horses. Creatinine may actually be elevated during the first 12 hours of life and then decreases. If azotemia, hypochloremia, hyponatremia, and hyperkalemia are found, ruptured bladder with uroperitoneum should be suspected. The creatinine concentration is preferable to BUN determination for diagnosis of this condition. Blood typing is useful for diagnosis of NI, determination of blood compatability between donor and transfusion recipient, and for verification of parentage for breed registries. Several techniques are available. Several tests are available for evaluation of the foal's immunoglobulin levels and confirmation of passive antibody transfer. Because foals suffering from FPT are more predisposed to infections, their immunoglobulin status should be determined as early as possible so that additional colostrum or plasma can be administered as needed. Neonatal isoerythrolysis is uncommon but is an important immunologic syndrome that often results in a fatal hemolytic crisis. If one suspects the condition may be likely, the optimal time for testing the mare is during the last 2 weeks of gestation. If the foal's dam is shown to have alloantibodies against a panel of known erythrocyte alloantigens, prevention is possible by feeding colostrum from another mare. If a foal develops NI, further colostrum ingestion from the dam must be prevented. Good nursing care, minimizing stress, and adequate frequent feedings are essential; prophylactic antibiotics should be used, and transfusion may be necessary.

Experimental production of neonatal isoerythrolysis in the foal.

Serological evidence with or without clinical signs of neonatal isoerythrolysis was experimentally produced in 6 of 8 foals born to mares allo-immunized with washed erythrocytes from the stallion. Blood group antigens were determined in all mares, stallions and foals, and the incompatible antigenic factor(s) responsible for the disease were defined. In 5 of 8 foals born to alloimmunized mares, a single antigenic factor difference accounted for the erythrocyte incompatibility between mare and foal. The erythrocyte antigen suspected as the most responsible for isoerythrolysis observed was A1. Agglutinin and hemolysin titers were measured in mare serum and colostrum. Of the presuckle anti-foal erythrocyte titers, colostral and hemolysins titers were greater than serum and agglutinin titers respectively. Foals were allowed to nurse and treatment of affected foals was not attempted which allowed full expression of disease and outcome.

Evaluation of a series of testing procedures to predict neonatal isoerythrolysis in the foal.

A series of modified (field) tests were compared to a crossmatch between mare and foal for their reliability in predicting neonatal isoerythrolysis (NI) in eight foals born to experimentally alloimmunized mares. In the field tests, mare's serum, plasma and colostrum were combined with foal erythrocytes washed by a modified procedure to determine which combination was the best predictor of impending NI. A consistent grading system for agglutination and hemolysis was employed. The field tests using mare's plasma demonstrated less agglutination and hemolysis than tests where serum was employed. Immediate assessment of agglutination failed to demonstrate agglutinin activity when compared to tests where incubation was included. Rouleaux formation posed a problem in interpretation of minor agglutination, however the grading of hemolysis was simpler, quicker, and more accurate. The field test that was most reliable when compared to the crossmatch and presuckle anti-foal erythrocyte titers in demonstrating agglutinins was the combination of mare's serum and foal's erythrocytes. The tests for hemolysin detection in serum and colostrum which incorporated rabbit sera as a complement source were also reliable.

Prevalence of anti-red blood cel antibodies in the serum and colostrum of mares and its relationship to neonatal isoerythrolysis.

The sera of 390 pregnant Standardbred mares and 409 pregnant Thoroughbred mares were tested for anti-red blood cell (RBC) antibodies. Of the Standardbred mares and Thoroughbred mares, 20% and 10%, respectively, had anti-RBC antibodies detectable in hemolytic or saline agglutination tests. Most of the antibodies were specific for the CA blood-group antigen of horses. Other antibodies were specific for the Aa, Ab, Aa, Ab, Da, Df, Ka, Ua, or Qa blood-group antigens. The occurrence of these antibodies in the serum and colostrum was compared for 268 mares. With 3 exceptions, whenever antibodies were found in 1 sample, they were found in the other. When a mare had antibodies to the Aa or Qa blood group antigens which were reactive at serum dilutions of 1:16 or greater, colostrum was withheld from that mare's foal. This practice seemed justified, because 1 foal which accidently received colostrum with anti-Aa antibodies developed neonatal isoerythrolysis. All other foals were allowed to nurse their mares' colostrum. None of them developed neonatal isoerythrolysis, even when anti-RBC antibodies were found for blood-group antigens other than Aa or Qa which reacted with the foals' RBC in in vitro tests.

Fatal hemolytic disease in sheep attributed to Leptospira interrogans serotype hardjo infection.

An outbreak of acute hemolytic disease in a large flock of sheep resulted in a mortality of approximately 5% in lambs. A diagnosis of Leptospira interrogans serotype hardjo infection was established on the basis of the presence of leptospires in the urine of one lamb, serologic findings in a guinea pig inoculated with this urine, L. hardjo titers in lambs, and pathologic findings. Prominent necropsy findings included severe icterus, thin watery blood, dark red to black kidneys and severe hemoglobinuria.

Counselling for genetic diseases of horses.

Dead or deformed foals produced by purebred parents represent an economic and emotional loss to the horse breeder. In order to avoid producing such defective foals in the future, the breeder may seek guidance in determining whether their origin is environmental or genetic. Only a few genetic diseases of horses have been rigorously defined. Selected, rare genetic diseases that prevent reproduction, cause the natural death, or necessitate the humane destruction of a foal before it fulfills its intended purpose serve as examples for collecting evidence to define the genetics of other deleterious diseases in the horse. In advising breeders how to avoid genetic defects in future foals, the professional needs to verify with appropriate evidence that the defect is genetic in origin, to discuss the mode of inheritance with the owners, and to advise them of the findings in writing so that they have a reference for making decisions.