Canine Von Willebrand's Disease: A Common Inherited Bleeding Disorder in Doberman Pinscher Dogs

Von Willebrand's disease is the most common inherited bleeding disorder of dogs occurring with particularly high frequency in Doberman pinscher dogs. Because of its method of transmission (autosomal incomplete dominant), the clinical and laboratory severity of the disease varies considerably. “Stress” may be required to make the increased bleeding tendency clinically apparent. This report describes five cases of Von Willebrand's disease in Doberman pinscher dogs and illustrates the variety of clinical expressions that the disease may take.     

Ovarian Disorders: Clinical and Morphological Observations in 30 Mares

A five year prospective study of equine ovarian problems requiring surgical correction was undertaken at the Ontario Veterinary College. Thirty mares were studied, of which 14 had granulosa cell tumors, six were with anovulatory persistent follicular “structures”, five had ovarian hemotoma, two presented ovarian hypoplasia and one each of ovarian dysgerminoma, teratoma and abscessation. The clinical signs manifested by the affected animals were varied. The affected ovaries were removed via flank or midline laparotomy or through colpotomy. Their morphology was studied and representative portions of affected ovaries submitted for laboratory diagnosis. Postsurgical recovery and resumption of reproductive activity were satisfactory.     

Historical aspects of Potomac horse fever in Ontario (1924–2010)

In the summer of 1924 Dr. Frank W. Schofield conducted investigations into an endemic disease of horses in the Kent and Essex counties of Ontario. According to farmers in these counties the disease had existed in this region for at least 50 years previously. The clinical, pathological, histopathological, and epidemiological findings outlined in Schofield’s detailed report strongly suggest that this endemic disease was what was designated in 1979 as “Potomac horse fever” (PHF). This assumption is further substantiated by transmission experiments involving horses and laboratory animals that were conducted by Schofield utilizing horse feces, whole blood, and mayflies. The aim of this paper is to present Schofield’s detailed investigations and findings and to compare these with PHF research conducted from 1979 to 2010 that ultimately led to the discovery of Neorickettsia risticii as the etiological agent and to elucidation of the organism’s complex life cycle.     

A hundred years of importation: The first animal quarantine station in North America; Lévis, Québec, 1876-1982

Quarantine, as a means of preventing disease importation, has been used for people and animals since the mid-19th century in Canada. The first animal quarantine facility in North America was established at Lévis, Québec in 1876. This quarantine station existed at Lévis until 1982 when it was closed and the function moved to Mirabel, Québec, near the International Airport. Veterinarians were in charge during the life of the Lévis Quarantine Station and some were also in charge of the Port of Quebec or a nearby District Office prior to the 1950's. In 1884 and 1886 the value of such a facility was illustrated in preventing the entry into Canada of contagious bovine pleuropneumonia and a vesicular disease. It was described in 1933 as “undoubtedly our most important quarantine station” and a year's operating costs as “trifling in comparison to losses which could occur if a foreign plague invaded this country”. This facility's history also illustrated the close veterinary and human medical cooperation during the early days of organized veterinary medicine in Canada. The station was an example for the establishment of other such facilities in North America.     

Glasser's Disease of Swine Produced by the Intratracheal Inoculation of Haemophilus suis

The intracheal inoculation of pigs with Haemophilus suis led to the production of Glasser's disease at every attempt without significant pulmonary involvement. Isolation of this organism from the experimental animals was possible only in the acute phase of the disease.

The indirect fluorescent antibody technique when applied to frozen sections of tissues obtained from the experimentally infected pigs at autopsy, revealed a few rod forms but mostly “round bodies” of H. suis in animals from which the organism was isolated, and “round bodies” only in the pigs from which the organism was not isolated.

Attention is drawn to the similarities between the lesions caused by H. suis and Mycoplasma hyorhinis, and to the confusion which may result therefrom. It is stressed that the laboratory diagnosis of these two diseases is complicated by the fact that both agents may not be isolated on the media commonly used in diagnostic laboratories. Both organisms necessitate the use of special media where the clinical and autopsy results indicate polyserositis and arthritis.

     

Inherited bleeding disorders of dogs and cats

The congenital bleeding disorders of domestic animals usually mimic closely the same disorders in man and are inherited in a similar fashion. Classical haemophilia (haemophilia A, factor VIII deficiency) and haemophilia B (factor IX deficiency) occur in both dogs and cats and are sex-linked conditions. Affected animals are almost always male and heterozygote females are asymptomatic carriers. Offspring of a carrier female have a 50 per cent chance of inheriting the defective X-chromosome and, on average, half of the sons will be affected and half of the daughters will be carriers. Diagnosis of affected animals is confirmed by specific factor assay. Carriers may be identified with a statistical certainty of greater than 80 per cent. Canine von Willebrand's disease is a less severe disorder due to a defect of platelet adhesion. It is an autosomal trait, inherited in most breeds in an incompletely dominant fashion.     

Heritability of plasma von Willebrand factor antigen concentration in German Wirehaired pointers

We applied quantitative genetic analyses to a population of German Wirehaired pointer dogs affected with type 2 von Willebrand disease. Plasma von Willebrand factor (vWF) protein concentration measured as vWF antigen (vWF:Ag), clinical history, and pedigree data were compiled for 331 dogs over a 5-year test period. Eight dogs had histories of abnormal bleeding and had markedly decreased plasma vWF:Ag concentrations (<1%). Four per cent of the dogs were inbred, with an average inbreeding of 2.52%. The estimated heritability of plasma vWF concentration was 0.52. We found a major gene effect on vWF concentration. Using a single gene locus model and two different prediction methods, the upper threshold value for the aa genotype was less than 1% vWF:Ag, and the optimal threshold value for discrimination between the AA and Aa genotypes was between 68% and 72% vWF:Ag. Our analyses indicate that phenotype, assigned on the basis of a single vWF:Ag determination, is heritable and can be applied for selective breeding in a von Willebrand disease test programme.     

Atrial fibrillation in ten cows

An irregular cardiac rhythm was identified in ten adult cows during auscultation of the heart and was subsequently characterized as atrial fibrillation by electrocardiography. The occurrence of the arrhythmia was associated with primary, organic disease of the heart in two animals which had valvular endocarditis. In seven of the other cows secondary or “functional” atrial fibrillation occurred in association with disorders of abdominal origin, six gastrointestinal disorders and one uterine torsion. Spontaneous conversion to normal sinus rhythm occurred in six cows after elimination of the primary disease.     

Effects of bilirubinemia, hemolysis, and lipemia on clinical chemistry analytes in bovine, canine, equine, and feline sera

Interferences caused by bilirubin, hemolysis, and lipemia on 25 clinical chemistry analytes in bovine, canine, equine, and feline sera were studied using the Coulter Dacos and commercial reagents. We present the data as “interferograms”, which show the anticipated percent change in serum analyte activity or concentration with varying concentrations of bilirubin, hemoglobin, or lipid. Obvious species differences in response to at least one added interfering substance were found for alanine aminotransferase, aspartate aminotransferase, cholesterol, creatine kinase, globulin, total protein, and urea. The remaining analytes were affected in a linear or complex dose-response relationship or were only affected at the highest concentrations of interfering substances. These data will be useful in aiding interpretation of laboratory test results when common interferences are present in the serum.     

Type III von Willebrand's disease in Dutch kooiker dogs

Summary

Type III von Willebrand's disease (vWD) was diagnosed in 38 Dutch kooiker dogs. Ten male and 9 female probands had been referred independently of each other to the Utrecht University Clinic for Companion Animals because of a moderate to severe bleeding tendency. Screening of 717 Dutch kooiker dogs, including 356 puppies, detected vWD in another 19 dogs. Diagnosis was based on non‐detectable amounts (< 1.6%) of von Willebrand factor antigen (vWF:Ag) in plasma by ELISA. Capillary bleeding time (CBT) was prolonged (> 10 min) and polybrene cofactor activity (vWF:PbCo) was not detectable in 11 dogs tested. No distinguishable protein bands were detected by multimer analysis. As in Scottish terriers with type III vWD, factor VIII clotting activity (F_VIII:C) in affected Dutch kooiker dogs was decreased but considerably less than in humans with type III vWD. A recessive mode of inheritance was indicated by the normal or subnormal but measurable amounts of vWF:Ag in the plasma of eight pairs of parents of affected dogs. The F₁ offspring resulting from the experimental mating of two affected dogs consisted of three affected males and four affected females. In 39 obligatory carriers vWF:Ag ranged from 30% to 114% with median and mean vWF values of 64% and 64.2%, respectively, and was subnormal (< 50%) in only 9 animals.     

Congenital Type III von Willebrand’s disease unmasked by hypothyroidism in a Shetland sheepdog

A 7-year-old, spayed female Shetland sheepdog had sudden onset of right-sided epistaxis. Diagnostic tests revealed Type III von Willebrand’s disease and primary hypothyroidism leading to an acute hypothyroid crisis and acquired factor VIII (FVIII) deficiency. Levothyroxine therapy normalized the serum thyroxine and FVIII concentrations. The delayed onset of disease and the reversible FVIII deficiency that was corrected with levothyroxine therapy, support a role for hypothyroidism in the pathogenesis of this dog’s sudden bleeding tendency as has been seen with hypothyroidism in humans.     

Pathological analysis of batch safety testing of veterinary vaccines using small laboratory animals

Batch safety tests (BSTs) of veterinary vaccines are conducted using small laboratory animals to assure the safety of vaccines according to several criteria, including clinical signs and change in body weight. Although the latter is used as an evaluation index in BSTs, there have been no reports on the internal changes that affect body weight during the test period. Therefore, we analyzed BST via pathological examination of the tested animals. Here, BSTs were performed for 176 batches using mice and 126 batches using of guinea pigs. Most of the gross findings could be classified into four lesion types (nodules, adhesions, ascites, no apparent signs), with only one vaccine inducing lesions that could not be classified into any of these four types. Histopathological examination revealed that the reactions caused by BST were pyogenic and/or granulomatous inflammation. Nodular or adhesive lesions comprised more severe pyogenic granulomatous inflammation than ascites or cases with no apparent gross lesions. These nodular or adhesive lesions were more frequently induced by vaccines that contained an adjuvant than by vaccines that did not contain an adjuvant. The cases with “exceptional” gross findings histologically presented severe necrosis of the hematopoietic system. Additional testing showed that these “exceptional” lesions were induced when a specific type of light liquid paraffin was injected along with other vaccine additives. Our results show that body weight loss and/or lesions during BST were induced by proinflammatory properties of the tested vaccines and that BST is a sensitive method for detecting unexpected effects of vaccine components.     

Bovine Leukosis II. Comparison of Hematological Classification with DNA Synthesis Between Herds

Blood samples of 126 mature cows with “persistent” hematological status from two leukosis herds and a leukosis free control herd were collected for determining hematological status and estimation of replicating lymphocytes. To quantitate the number of DNA synthesizing cells, the blood was incubated with tritiated thymidine in vitro followed by autoradiography. Classification of animals according to lymphocytosis status did not reveal clearly whether or not a difference existed between the two leukosis herds. The estimation of DNA synthesizing lymphocyte counts showed that the animals from the two leukosis herds did not differ from each other while differing significantly from control herd animals. The study suggests that the similarities between the two leukosis herds, while ambiguous on lymphocyte counts alone, become clear when DNA synthesizing cell counts are compared. Thus the animals of the two leukosis herds belonged to the same “leukosis” population.     

Business intelligence tools to optimize the appropriateness of the diagnostic process for clinical and epidemiologic purposes in a multicenter veterinary pathology service

Laboratory tests provide essential support to the veterinary practitioner, and their use has grown exponentially. This growth is the result of several factors, such as the eradication of historical diseases, the occurrence of multifactorial diseases, and the obligation to control endemic and epidemic diseases. However, the introduction of novel techniques is counterbalanced by economic constraints, and the establishment of evidence- and consensus-based guidelines is essential to support the pathologist. Therefore, we developed standardized protocols, categorized by species, type of production, age, and syndrome at the Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), a multicenter institution for animal health and food safety. We have 72 protocols in use for livestock, poultry, and pets, categorized as, for example, “bovine enteric calf”, “rabbit respiratory”, “broiler articular”. Each protocol consists of a panel of tests, divided into ‘mandatory’ and ‘ancillary’, to be selected by the pathologist in order to reach the final diagnosis. After autopsy, the case is categorized into a specific syndrome, subsequently referred to as a syndrome-specific panel of analyses. The activity of the laboratories is monitored through a web-based dynamic reporting system developed using a business intelligence product (QlikView) connected to the laboratory information management system (IZILAB). On a daily basis, reports become available at general, laboratory, and case levels, and are updated as needed. The reporting system highlights epidemiologic variations in the field and allows verification of compliance with the protocols within the organization. The diagnostic protocols are revised annually to increase system efficiency and to address stakeholder requests.     

Von Willebrand's factor deficiency in a random population of Danish golden retrievers

The incidence of deficiency of von Willebrand's factor, the cause of von Willebrand's disease, the most common, mild, inherited bleeding disorder of people and animals was documented in a random population of Danish Golden Retrievers. Using a rabbit, anticanine von Willebrand protein antibody and a rocket immunoelectrophoretic technique, 68 dogs were examined. Eighteen percent, 12 dogs, had statistically and significantly (P less than 0.01) low concentrations of the von Willebrand protein and were considered carriers or deficients. These findings in this modest population should raise the clinical index of suspicion concerning this disease and other disease processes associated with it.     

The pathogenesis and pathology of bovine tuberculosis with insights from studies of tuberculosis in humans and laboratory animal models

This paper reviews key insights the discipline of pathology has contributed to our understanding of bovine tuberculosis in the context of findings of studies of tuberculosis in humans and laboratory animal models. Analysis and extrapolation of data from other species have the potential to expand our understanding of the pathogenesis of the disease in cattle. The distribution of lesions in affected cattle, humans and laboratory animals illustrate the primacy of the respiratory tract as portal of infection and raise questions about the role of the upper respiratory tract surface, tonsil and dorsal lung regions in disease pathogenesis and transmission. The mechanisms behind significant pathological processes such as necrosis, apoptosis and liquefaction, occurring within lesions, are explored and their potential practical significance assessed in the context of herd disease dynamics and vaccine development. It is proposed that effective 'innate' host defences result in many animals and humans remaining disease-free and tuberculin test negative following exposure to infection. Furthermore, the concepts of latency and disease reactivation, considered significant factors in perpetuating tuberculosis in human populations, are explored in the context of the bovine disease.     

The Veterinary Practitioner and Diseases Exotic to Canada

Veterinarians, in clinical practice, regulatory field work, laboratory diagnosis or research, must work together as a team, each within his area of expertise in order to protect the livestock industry of Canada from exotic diseases. This freedom from many of the serious animal plagues has allowed the development of intensive animal production units with increased vulnerability to disease and in which the impact of disease outbreaks may be more serious.In differential diagnoses one should think not only of the classical exotic diseases such as vesicular diseases, swine fever and rinderpest in today''s world, but one should constantly be on the outlook for any disease outbreak that does not quite fit the picture of the domestic diseases. From this standpoint the large animal practitioner is the very important “first line of defense” since, in all likelihood, he will be the first to see a disease exotic to Canada should that disease gain entry.     

Canine hypoadrenocorticism: Part I

Hypoadrenocorticism (Addison’s disease) has been referred to as “the great pretender,” due to its ability to mimic other common diseases in the dog and thereby represent a diagnostic challenge. Naturally occurring hypoadrenocorticism is an uncommon canine disease. Young, female dogs are overrepresented. Hypoadrenocorticism typically results from immune-mediated destruction of all adrenocortical layers, resulting in deficiencies of min-eralocorticoids (aldosterone) and glucocorticoids (cortisol). A small number of dogs suffer from glucocorticoid deficiency only. Dogs suffering from hypoadrenocorticism may present in a variety of conditions, from a mildly ill dog to a shocky and recumbent dog. This review discusses etiology, pathophysiology, history, physical examination findings, and diagnostic findings in the Addisonian patient. A follow-up article (Part II) will discuss the definitive diagnosis and management strategies for these patients.     

Corynebacterium pseudotuberculosis infection in goats. II. The prevalence of caseous lymphadenitis in 36 goat herds in Northern Norway

The precalen-ce of caseous lymphadenitis was surveyed in 36 goat herds in Northern Norway. In each herd, information concerning the occurrence of the disease was obtained from the farmer. Adult animals (1 year of age or older) in 35 herds were examined for superficial swellings, and serum samples were collected from most animals in the herds. The sera were examined for antibodies to Corynebacterium pseudotuber-culosis using the bacterial agglutination test (BAT) and the hemolysis inhibition test (HIT).Gaseous lymphadenitis was diagnosed with certainty in 19 herds. Information from the farmers indicated that the disease indeed oc-curred in these herds, and that the majority had been infected with the disease for many years. The herds had apparently become infected through contact with animals from infected herds. Clinical examina-tions were carried out in 18 of these herds and superficial swellings were found in 26 % of the examined animals. The prevalence of ani-mals with lesions varied from 11 to 40 % among the herds. Of the animals in these herds, 81 % were positive in BAT and 84 % in HIT. The prevalence of positive animals varied from 26 to 99 % in BAT and 28 to 99 % in HIT. The prevalence of seropositive animals was lowest in a herd in which animals were kept separately in stalls.Caseous lymphadenitis could not be diagnosed in 16 herds. In-formation from the farmers indicated that the disease indeed seemed to be absent in 14 of these herds. These 14 herds had no history of contact with animals from herds considered to be infected. However, in the remaining 2 herds, the farmers were somewhat uncertain about the occurrence of the disease. One of these 2 herds had a history of contact with infected herds through participation in a goat “breeding circle”. Only a few of the animals were, however, seropositive and all these had low antibody titres.In 1 newly established herd, a single animal showed a high posi-tive titre in BAT only. All the other animals were negative in both tests. This particular herd consisted of animals obtained both from herds with caseous lymphadenitis and from herds in which the disease was not considered to occur.