Von Willebrand's Disease in Two Families of Doberman Pinschers

The history, clinical symptoms and laboratory results in two families of Doberman pinschers with von Willebrand's disease are described. The affected animals illustrate the rather nonspecific bleeding problems that may be encountered in mild and moderate forms of this disease. In both families a bleeding diathesis was suspected when one member of the family underwent surgery with serious postoperative bleeding complications. These cases illustrate the importance of a thorough presurgical history as well as the necessity for specific laboratory assays of F VIII including von Willebrand factor activity for the recognition of affected and “carrier” animals.     

Inheritance of von Willebrand's disease in a colony of Doberman Pinschers

OBJECTIVE: To determine the mode of inheritance of von Willebrand's disease (vWD) and perform linkage analysis between vWD and coat color or narcolepsy in a colony of Doberman Pinschers. ANIMALS: 159 Doberman Pinschers. PROCEDURE: von Willebrand factor antigen (vWF:Ag) concentration was measured by use of ELISA, and results were used to classify dogs as having low (< 20%), intermediate (20 to 65%), or high (> 65%) vWF:Ag concentration, compared with results of analysis of standard pooled plasma. Buccal bleeding time was measured, and mode of inheritance of vWD was assessed by pedigree analysis. RESULTS: von Willebrand's disease was transmitted as a single autosomal gene defect. Results suggested that 27.04% of dogs were homozygous for vWD, 62.26% were heterozygous, and 10.69% did not have the defect. Most homozygous and some heterozygous dogs had prolonged bleeding times. Dogs with diluted coat colors (blue and fawn) were significantly overrepresented in the homozygous group, compared with black and red dogs, but a significant link between vWD and coat color was not detected. CONCLUSIONS AND CLINICAL RELEVANCE: von Willebrand's disease is transmitted as an autosomal dominant trait with variable penetrance; most dogs in this colony (89.3%) were carriers of vWD. Homozygosity for vWD is not likely to be lethal. Some heterozygous dogs have prolonged bleeding times. An association between diluted coat colors and vWD may exist.     

Canine von Willebrand's disease. A heterogeneous group of bleeding disorders

The term "von Willebrand's disease," refers to a group of inherited bleeding disorders, all of which are caused by a deficiency of the multimeric plasma glycoprotein, von Willebrand factor. The various forms of canine von Willebrand's disease can be categorized into one of three major types: in type I canine von Willebrand's disease, all sizes of von Willebrand factor multimers can be detected in the plasma; in type II canine von Willebrand's disease, only the smaller von Willebrand factor multimers are found in the plasma (larger multimers are absent); and in type III canine von Willebrand's disease, von Willebrand factor is completely absent from the plasma or present in only trace amounts. Von Willebrand's disease is common in dogs, but some forms of the disease are so mild that they are of questionable clinical significance.     

Kinematic characteristics of myositis ossificans of the semimembranosus muscle in a dog

A 6-year-old Doberman pinscher dog was presented with myositis ossificans of the semimembranosus muscle. Linear, temporal, and angular kinematic patterns were recorded and compared with those of sound dogs of the same breed. The results indicate that the specific gait compensations occurring with this disease may aid in the diagnosis of myositis ossificans of the caudal thigh muscles.     

Familial Glomerulonephritis in Doberman Pinscher Dogs

Progressive renal disease in 13 related Doberman pinscher dogs had the histological criteria of membranoproliferative glomerulonephritis. Polyuria, polydipsia and weight loss were the usual initial abnormalities and were observed at one year of age or less in seven of 11 dogs diagnosed antemortem as having renal disease. There was no sex predilection. All dogs were traced to a common male dog no more than four generations previously.     

Von Willebrand's disease in dogs

Von Willebrand's disease, the most common, mild, inherited bleeding disorder of animals, is an autosomal trait generally causing high morbidity and low mortality and affecting many breeds of dogs. Clinical signs include hematuria, epistaxis, gingival or genital mucosal bleeding, lameness, and prolonged bleeding from cut nails or wounds. Concurrent hypothyroidism exacerbates the disease. Affected dogs and carriers should not be bred or should be tested for von Willebrand's factor before breeding. Treatment involves IV infusion of fresh whole blood or plasma, at 3-5 ml/lb, with topical use of hemostatic compounds, and avoidance of drugs that interfere with hemostasis.     

Effect of Desmopresssin in Normal Dogs and Dogs with von Willebrand's Disease

Desmopressin acetate (DDAVP(R)), a synthetic analogue of vasopressin was slowly administered intravenously to 12 healthy dogs of various breeds and 10 Doberman Pinschers with mild-to-moderate type I von Willebrand's disease at a dose of 0.3, 1.0 and 3.0 micro g/kg body weight. Plasma von Willebrand factor:antigen was measured by an electroimmunoassay prior to and 30, 60, 90, 120 and 180 minutes after desmopressin infusion. Desmopressin induced only very modest and statistically insignificant increases in von Willebrand factor in both groups. We conclude that the response to desmopressin as measured by circulating von Willebrand factor is much less pronounced in healthy dogs and in Doberman Pinschers with von Willebrand's disease than in humans.     

Epidemiologic features of von Willebrand's disease in Doberman pinschers, Scottish terriers, and Shetland sheepdogs: 260 cases (1984-1988)

During a study period from 1985 through 1988, plasma von Willebrand's factor antigen (vWF:Ag) concentration was measured as a marker for prevalence of the von Willebrand's disease (vWD) trait in Doberman Pinschers (doberman, n = 5,554), Scottish Terriers (scottie, n = 1,363), and Shetland Sheepdogs (sheltie, n = 4,279). Significant increase in prevalence of the trait was seen in scotties and shelties during this period. In 1988, 73% of dobermans, 30% of scotties, and 28% of shelties tested had abnormal vWF:Ag concentration (less than 50% vWF:Ag). We found significant differences between breeds with respect to age and vWF:Ag concentration of clinically affected dogs at time of diagnosis. The affected dobermans were older (doberman mean age, 4.6 years; scottie mean age, 1.7 years; sheltie mean age, 1.9 years) and had higher concentration of plasma vWF:Ag (doberman mean vWF:Ag, 15%; scottie mean vWF:Ag, 0%; sheltie mean vWF:Ag, 8%). Bleeding in affected dogs of all 3 breeds was observed predominantly from mucosal surfaces and from cutaneous sites of surgery or trauma. The most common site of mucosal bleeding in scotties and shelties was oral or nasal cavity, and in dobermans was the urogenital tract. Differences in clinical manifestations of vWD in purebred dogs may reflect heterogeneous defects within the vWF gene, causing a variety of abnormalities in production, structure, and function of vWF protein. Analogous to vWD in human beings, acquired deficiencies of vWF may also contribute to the clinical variability of vWD in dogs.     

Von Willebrand's disease in the German shepherd dog

Two litters of German shepherd dogs were evaluated for a haemorrhagic tendency that was characterised by excessive bleeding from the umbilicus at birth, haemorrhage and haematoma formation at vaccination, excessive bruising, and lameness due to haemarthrosis. Platelet counts, clotting times and Von Willebrand's factor (VWF) assays were assessed in all dogs. Factor VIII determination was performed in 1 puppy and its parents. Based on the clotting times and VWF assay, 6 puppies (4 male and 2 female) showed type I Von Willebrand's disease (VWD), 5 (4 male and 1 female) possible type II VWD, and 4 were unaffected. One puppy with possible type II VWD had very low factor VIII activity; its sire had a normal factor activity, whereas the dam was in the low-normal range. This article reports type I and possible type II VWD in 2 related litters of German shepherd dogs, the latter being rare in German shepherd dogs.     

Detection of von Willebrand's Disease in Dogs with a Rapid Qualitative Test, Based on Venom-Coagglutinin-Induced Platelet Agglutination

A rapid, qualitative blood test was developed to identify potential bleeders among dogs that are von Willebrand's disease suspects. The test, based on venom coagglutinin-induced agglutination of formalin-fixed washed platelets, was compared to the more lengthy electroimmunoassay for factor VIII-related antigen. The 2 tests were performed on plasma samples from 82 dogs, including 68 Doberman pinschers. The 39 plasma samples that were found to be "clinically normal" by the new test had factor VIII-related antigen concentrations ranging from 32% to 192% of that in a pool of normal canine plasma samples. Plasma samples from the 43 dogs that tested as "potential bleeders" by the new test had factor VIII-related antigen concentrations from 4% to 38%. All 43 "potential bleeders" were Doberman pinschers. Shortly after being evaluated by the new test, 46 of the dogs underwent invasive diagnostic, therapeutic, or cosmetic procedures. Excessive hemorrhage was encountered in 40% of the 25 dogs that tested as "potential bleeders. " In contrast, only 5% of the 21 dogs that tested as "clinically normal" exhibited abnormal bleeding.     

COMPUTED TOMOGRAPHY IN THE EVALUATION OF CAUDAL CERVICAL SPONDYLOMYELOPATHY OF THE DOBERMAN PINSCHER

Caudal cervical spondylomyelopathy is a common neurologic disorder of Doberman pinschers which has a number of striking similarities to cervical spondylotic myelopathy in humans. Diagnosis of this human disease is facilitated considerably by the use of computed tomographic (CT) myelography. Sixteen Doberman pinscher dogs with caudal cervical spondylomyelopathy were studied by conventional myelography followed by CT myelography. A close correlation was noted between the CT myelographic appearance of the cervical spinal cord in these dogs, and that reported for human cervical spondylotic myelopathy. Five dogs had atrophy of the spinal cord, and in another there was an accumulation of contrast medium within the spinal cord. These features are often associated with a poor response to surgical decompression in humans with cervical spondylotic myelopathy. The CT examination provided information that could not be obtained by conventional myelography alone and should be considered as an additional diagnostic procedure in dogs with caudal cervical spondylomyelopathy.     

Dilated cardiomyopathy (DCM) in dogs--pathological, clinical, diagnosis and genetic aspects

Dilated cardiomyopathy (DCM) is a heart disease which is often found in humans and animals. The age of onset of this progressive disease varies between 3 and 7 years of age. A juvenile form of DCM has been found in Portuguese Water Dogs and Doberman Pinscher Dogs. Some breeds such as Doberman pinscher, Newfoundland, Portuguese Water dog, Boxer, Great Dane, Cocker Spaniel and Irish Wolfhound exhibit a higher prevalence to DCM. There also seems to be a sex predisposition as male dogs are affected more often than female dogs and in Great Danes an X-linked recessive inheritance is likely. In Newfoundland and Boxer an autosomal dominant inheritance was found whereas an autosomal recessive inheritance was described in Portuguese Water Dogs. Atrial fibrillation as a cause or consequence of DCM is assumed for certain breeds. The causes of DCM are widely unknown in dogs. A genetic basis for this heart disease seems to exist. Apart from a few exceptions the mode of inheritance and the possible underlying gene mutations are not known for DCM in dogs. In humans mutations in several genes responsible for DCM have been identified. Comparative genetic analyses in dogs using genes causing DCM in men and a genome-wide scan with anonymus markers were not able to detect causative mutations or genomic regions harboring gene loci linked to DCM. The investigation of the genetic basis of canine DCM may lead to new insights into the pathogenesis of DCM and may result in new therapeutic approaches and breeding strategies.     

Effect of Desmopressin Acetate on Bleeding Times and Plasma von Willebrand Factor in Doberman Pinscher Dogs with von Willebrand''s Disease

Effects of desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]) on plasma von Willebrand factor (vWf) were studied in 12 purebred Doberman pinschers confirmed to have von Willebrand's disease (vWd) (plasma vWf antigen [vWf:Ag] concentrations, less than 30 U/dl). Twelve dogs had subnormal plasma botrocetin cofactor (BCf) activity and 11 dogs had prolonged buccal mucosa bleeding times. Tranquilization of three dogs with lenperone and three dogs with xylazine did not induce significant changes in mean plasma vWf:Ag concentrations or mean BCf activities. Thirty and 120 minutes after administration of DDAVP (1 micrograms/kg subcutaneously), there was significant shortening of the mean buccal mucosa bleeding time. Ten dogs responded to DDAVP with increases in BCf activity which exceeded 10 U/dl at 30 or 120 minutes, or both, after the drug was administered. At the same time, increases in plasma vWf:Ag concentrations were smaller than the increases in BCf activity. It was shown by multimeric analysis that primarily the higher molecular weight forms of vWf increased in plasma in response to DDAVP.     

Potential central nervous system complications of von Willebrand's disease.

Three Doberman pinschers were presented on emergency referral for progressive neurological deficits. All three dogs had a similar onset of clinical signs associated with an apparently minor traumatic event. Each dog progressed to significant neurological dysfunction including paraplegia, tetraplegia, and/or loss of deep pain sensation. None of the animals was apparently affected by cervical vertebral instability ("Wobbler's Syndrome"). All were confirmed to have von Willebrand's disease. In all cases, significant epidural hemorrhage was identified. The etiology of each hemorrhage, however, was different for each animal. The cases presented here demonstrate a potential relationship between neurological deficits and the patient's ability to effectively coagulate blood. Hemostatic abnormalities, such as von Willebrand's disease, should be included as possible differential diagnoses or contributing factors in animals demonstrating neurological deficits. These abnormalities should especially be considered following trauma, intervertebral disk extrusion, or spinal surgery.     

A retrospective study of heart disease in doberman pinscher dogs

The prevalence of gross and/or histological cardiac lesions was found to be much greater in Doberman pinscher dogs (16/26 or 62%) than in non-Doberman dogs (124/417 or 30%). At least some of the affected Dobermans were unrelated. Middle aged (mean age 4.7 yr) Dobermans of both sexes (11 M:5F) were affected. Four of the Dobermans with heart lesions had congestive cardiomyopathy; three of these four had congestive heart failure and the other one died suddenly. Prominent gross lesions were ventricular dilation and atrioventricular valvular endocardiosis. Histological lesions noted were prominent myocardial fibrosis, myofiber degeneration with fatty replacement, myofiber vacuolation and arterial intimal cushion formation. A spectrum of myocardial disease exists in Dobermans and clinically overt congestive cardiomyopathy represents one end of this spectrum.     

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.     

Color dilution alopecia in a blue Doberman pinscher crossbreed

A 6-year-old male, blue Doberman pinscher crossbreed was presented with coat abnormalities; in particular, flank alopecia and pruritus. Based on medical the history, clinical evidence, and histopathological examination, color dilution alopecia was diagnosed. The dog was with oral melatonin treated for 3 months without success.     

von Willebrand disease phenotype and von Willebrand factor marker genotype in Doberman Pinschers

OBJECTIVE: To define the relationship between clinical expression of a type-1 von Willebrand disease phenotype and genotype at 2 von Willebrand factor marker loci in Doberman Pinschers. ANIMALS: 102 client-owned Doberman Pinschers. PROCEDURES: Dogs were recruited on the basis of plasma von Willebrand factor concentration, clinical history, and pedigree. Blood samples and response to a history questionnaire were obtained for each dog. Plasma von Willebrand factor concentration was measured by use of an ELISA, and genotyping was performed via polymerase chain reaction for 1 intragenic and 1 extragenic von Willebrand factor marker. Amplification product size was determined by use of polyacrylamide gel electrophoresis (intragenic marker) or automated sequence analysis (extragenic marker). Western blots were prepared from a subset of dogs with low plasma von Willebrand factor concentration to evaluate multimer distribution. RESULTS: Strong associations were detected between plasma von Willebrand factor concentration and von Willebrand factor marker genotype. Twenty-five dogs had substantial reduction in plasma von Willebrand factor concentration and multiple hemorrhagic events. All were homozygous for a 157-base-pair intragenic marker allele and homozygous or compound heterozygous for 1 of 4 extragenic marker alleles. These marker genotypes were exclusively detected in dogs with low plasma von Willebrand factor concentration, although some dogs with these genotypes did not have abnormal bleeding. CONCLUSIONS AND CLINICAL RELEVANCE: Type-1 von Willebrand disease in Doberman Pinschers is associated with the von Willebrand factor gene locus; however, the expression pattern in this breed appears more complex than that of a simple recessive trait.     

Buccal mucosa bleeding times of healthy dogs and of dogs in various pathologic states, including thrombocytopenia, uremia, and von Willebrand's disease

The buccal mucosa bleeding time (BMBT; duration of hemorrhage from standardized cuts made with a spring-loaded disposable device in the mucosal surface of the upper lip) was used to evaluate the hemostatic competence of dogs. The mean (+/- SD) BMBT for 34 healthy dogs was 2.62 +/- 0.49 minutes. The BMBT of healthy dogs anesthetized with halothane or tranquilized with xylazine were not significantly different from the BMBT of healthy dogs evaluated without chemical restraint. The BMBT was significantly (P less than 0.01) prolonged 21 hours after aspirin (10 mg/kg of body weight) was administered orally to 10 healthy dogs; however, the mean aspirin-induced increase in BMBT was only 0.40 minutes. The BMBT of 28 of 30 dogs with various diseases not traditionally associated with hemostatic deficiencies were near or within the range of BMBT for healthy dogs; however, 2 dogs had BMBT of greater than 8 minutes. In contrast, BMBT were prolonged in most dogs with diseases known to induce deficient primary hemostasis; the 3 dogs with thrombocytopenia (less than or equal to 20,000 platelets/microliter), the 7 Doberman Pinschers with von Willebrand's disease (von Willebrand factor antigen; less than or equal to 18 U/dl), and 5 of the 6 dogs with severe azotemia (serum urea nitrogen; greater than or equal to 124 mg/dl) had prolonged BMBT. The BMBT of 16 dogs were determined immediately before they were subjected to various surgical procedures, and the severity of the hemorrhage encountered during these procedures was subjectively evaluated; the amount of hemorrhage from 12 of the 16 dogs was considered to be appropriate for the corresponding surgical procedures, but the remaining 4 dogs bled excessively during surgery.(ABSTRACT TRUNCATED AT 250 WORDS)