Plasma von Willebrand factor concentration and thyroid function in dogs

Plasma von Willebrand factor antigen concentration was determined in 15 dogs with suspected hypothyroidism, in 1 dog with hyperthyroidism, and in 14 euthyroid dogs. The mean +/- SEM von Willebrand factor:antigen concentration in hypothyroid dogs (47.1% +/- 12.6%) was significantly decreased (P less than 0.0005), compared with that in euthyroid dogs (94.7 +/- 5.6%). Four hypothyroid dogs were given thyroxine for 1 month and all 4 had an increase in von Willebrand factor:antigen concentration. The plasma von Willebrand factor:antigen concentration was 200% in the hyperthyroid dog. Seemingly, reduced concentrations of plasma von Willebrand factor:antigen can be found in dogs in association with congenital von Willebrand disease or with von Willebrand disease acquired through hypothyroidism.     

Effect of desmopressin on plasma factor VIII and von Willebrand factor concentrations in Greyhounds

Objective To determine the effect of 1-Deamino-8-D-argi-nine vasopressin on plasma concentrations of von Willebrand factor and factor VIII in Greyhound blood donors, and to compare the response of 1-Deamino-8-D-arginine vaso-pressin injection on plasma concentrations of von Willebrand factor between groups with different resting plasma concentrations of von Willebrand factor.
Animals Fifteen Greyhound blood donors were used. Dogs were grouped into three categories depending on their von Willebrand factor concentrations.
Procedure Desmopressin was administered subcuta-neously at 1 mg/kg to all dogs. Plasma von Willebrand factor and factor VIII concentrations were measured before and 10, 20, 30, 45, 60, 90 and 120 min after desmopressin injection.
Results The von Willebrand factor and factor VIII concentrations in all dogs increased significantly and remained higher than base-line throughout the 2 h period.
Conclusion Desmopressin is useful in increasing von Willebrand factor concentrations in Greyhound blood donors, including those with low resting concentrations.     

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.     

Bleeding disorder (von Willebrand disease) in a quarter horse

Bleeding diathesis in a Quarter Horse filly was caused by von Willebrand disease. Hemorrhage occurred mainly from mucosal surfaces and after trauma. Quantitative and qualitative measurements of plasma von Willebrand factor (vWF) documented a specific deficiency of vWF high molecular weight multimers, and concurrently greater than expected deficiency of vWF activity relative to vWF concentration. These findings are characteristic of type-II von Willebrand disease in human beings. Application of vWF assays used in human and small animal medicine now permits evaluation of vWF and diagnosis of von Willebrand disease in horses with bleeding disorders.     

Failure of sodium pentobarbital anesthesia to alter 1-desamino-8-D-arginine vasopressin-induced elevations of plasma factor VIII/ von Willebrand factor in normal dogs.

The vasopressin analog 1-desamino-8-D-arginine stimulates elevations in plasma Factor VIII/ von Willebrand factor in normal dogs. In order to study the effects of general anesthesia on this response, six dogs were anesthetized with sodium pentobarbital or given an equivalent amount of saline then challenged with an intravenous dose of 1-desamino-8-D-arginine (0.6 micrograms/kg body weight). Factor VIII coagulant activity, von Willebrand factor antigen, and ristocetin cofactor activity were quantitated before anesthesia (or saline infusion), 20 min after induction (pre-1-desamino-8-D-arginine), and at 30 and 60 min post-1-desamino-8-D-arginine. Anesthesia did not significantly affect the elevations in plasma Factor VIII/ von Willebrand factor induced by 1-desamino-8-D-arginine. Sodium pentobarbital appeared however to prevent the rise in Factor VIII coagulant activity seen following saline treatment. The results of this study suggest that when 1-desamino-8-D-arginine is to be used in normal dogs to boost basal plasma von Willebrand factor levels, it is not necessary to administer it prior to induction of general anesthesia with sodium pentobarbital.     

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.     

DNA testing for type III von Willebrand disease in Dutch Kooiker dogs

Von Willebrand disease type III is widespread in Dutch Kooiker dogs. To eradicate von Willebrand disease from the breed, affected dogs and nonsymptomatic carriers must be excluded from breeding. Previous efforts to detect carriers in Kooiker dogs by a von Willebrand factor antigen assay were not satisfactory because of considerable overlap of plasma concentrations in normal dogs and carriers. The aim of this study was to develop and apply a DNA test for the detection of von Willebrand disease carriers in the Kooiker breed. Two mutations in the von Willebrand factor gene in affected Kooiker dogs have been described previously, a splice site mutation at the border of intron 16 and exon 16 and a missense mutation in exon 3. We have developed polymerase chain reaction tests for both mutations in genomic DNA. The missense mutation most likely is a neutral variant and appears to be a polymorphism present in many breeds. The allele-specific oligonucleotide test for the splice site mutation was applied in the selection of animals cleared to breed by the Dutch breeding club. In a few years, the mutation has been eliminated from the breeding stock without apparent increase of inbreeding or preferential sire usage.     

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.     

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.     

Effect of acepromazine, xylazine and thiopentone on factor VIII activity and von Willebrand factor antigen concentration in dogs

The effect of acepromazine maleate, xylazine and thiopentone on the packed cell volume, plasma protein content, factor VIII activity and von Willebrand factor antigen concentration of blood was studied in normal dogs. The same variables were measured in dogs with haemophilia A given acepromazine maleate and thiopentone. Both the packed cell volume and plasma protein content decreased after the administration of either acepromazine maleate or xylazine. Values were not changed further after administration of thiopentone. Changes in the haemostatic variables measured were generally small. Consequently, blood samples collected from dogs under the influence of premedicant doses of acepromazine maleate or xylazine, and when subsequently anaesthetised with thiopentone, are adequate for the assay of factor VIII activity and von Willebrand factor antigen concentration for establishing an animal's haemophilia A and von Willebrand's disease status.     

von Willebrand factor in lysates of washed canine platelets

Canine and human platelets (washed 4 times in a solution containing EDTA, prostaglandin E1, and theophylline to prevent release of alpha-granule constituents) were lysed by being frozen and thawed in the presence of detergent. Radioelectroimmunoassay for von Willebrand factor (vWf) in 5 human platelet lysates produced precipitin rockets, shaped like those produced from vWf in plasma from healthy human beings, and indicated that the mean von Willebrand factor antigen (vWf:Ag) content in platelets from healthy human being was 526 +/- 87 human U/10(12) platelets. Radioelectroimmunoassay for vWf in platelet lysates from 17 healthy dogs with normal plasma. vWf:Ag concentration produced precipitin rockets that looked different from those produced from canine plasma and indicated vWf:Ag content of 59 +/- 35 canine U/10(12) platelets. Inclusion of protease inhibitors in the lysing solution did not normalize the appearance of the precipitin rockets or substantially alter the measured platelet content of vWf:Ag. The array of vWf multimers revealed by sodium dodecyl sulfate-agarose gel electrophoresis of canine platelet lysates had a distinct appearance that differed from that of vWf in canine or human plasma and platelets; the intensity of the canine platelet vWf multimer bands was skewed, with relatively greater density in the lower molecular weight region and faint or undetectable multimer bands in the higher molecular weight region. Electrophoretograms with visible multimers in the high molecular weight region had vWf components that had higher molecular weight than did any vWf components in canine plasma. Radioelectroimmunoassay for fibronectin in these same canine platelet lysates indicated that the fibronectin content in platelets was 2.89 +/- 1.10 mg/10(12) platelets.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Von Willebrand's disease in dogs in the United Kingdom

An assay for the measurement of von Willebrand factor antigen has been established. In a period of 18 months, 13 dogs have been identified as suffering from von Willebrand's disease. The affected animals had levels of von Willebrand factor antigen which ranged from undetectable to 43 per cent of normal. Factor VIII levels were also reduced. Haemorrhagic episodes were usually associated with trauma or surgery, and often required transfusion with fresh blood or plasma to arrest haemorrhage.     

von Willebrand heterotopic osteochondrofibrosis in Doberman pinschers: five cases (1980-1987)

Five cases involving female Doberman Pinschers, each with a mass composed of osseous, chondrous, or fibrous tissue, or a combination thereof, formed in or around the muscles of the hip, were reviewed. In each dog, the mass severely limited the coxofemoral joint range or motion, especially when the joint was extended. Surgical debulking resulted in a favorable outcome. All dogs tested had plasma concentrations of von Willebrand factor antigen below established normal limits. We believe that the low concentrations of von Willebrand factor antigen commonly found in Doberman Pinschers may predispose them to the development of this condition and its resulting pelvic limb lameness, presumably because of increased risk of microvascular bleeding. This association is presumptive because 2 dogs in our study had a history of excessive bleeding either before or after being treated for the hip condition. Trauma was associated in 2 cases. All 5 dogs, however, bled more than usual during the curative surgery. These 5 cases, plus additional reported cases, confirm this syndrome, which warrants recognition. The name von Willebrand heterotopic osteochondrofibrosis of Doberman Pinschers was selected because it identified the basic features of the syndrome.     

Desmopressin enhances the binding of plasma von Willebrand factor to collagen in plasmas from normal dogs and dogs with type I von Willebrand's disease.

A new in vitro von Willebrand factor-collagen binding activity (vWF:CBA) assay was used to assess qualitative changes in vWF in normal dogs and dogs with Type I von Willebrand's disease (vWD) following treatment with desmopressin acetate (DDAVP). Although DDAVP induced increases in vWF antigen concentrations at 1 hour postinfusion in both normal and vWD dogs (57% and 60% increases, respectively), there were disproportionately greater increases in vWF:CBA (96% and 103% increases). These results support the hypothesis that the enhanced hemostatic activity induced by DDAVP is, at least in part, due to the selective release of more functionally active vWF multimers. The assay, as described, provides a convenient means of simultaneously assessing vWF quantity and function before and after DDAVP administration.     

Development of a collagen-binding activity assay as a screening test for type II von Willebrand disease in dogs

OBJECTIVE: To develop an assay to measure canine von Willebrand factor (vWF):collagen-binding activity (CBA) to screen for type 2 von Willebrand disease (vWD) in dogs. SAMPLE POPULATION: 293 plasma samples submitted for analysis of canine vWF antigen (vWF:Ag) and 12 control plasma samples from dogs with inherited type 2 or 3 vWD. PROCEDURE: Bovine collagens were evaluated for suitability as binding substrate for vWF. Assay sensitivity to depletion, proteolytic degradation, or a genetic deficiency of high-molecular-weight vWF were determined. Amounts of vWF:Ag and vWF:CBA were measured. The ratio of vWF:Ag to vWF:CBA was used to discriminate between type 1 and type 2 vWD. RESULTS: An assay for canine vWF activity was developed by use of mixed collagen (types I and III). When vWF:Ag was used to subtype vWD, 48% of the dogs were classified as clinically normal, 9% as indeterminate, and 43% as type 1 vWD. Inclusion of vWF activity resulted in reclassification of 5% of those identified as type 1 to type 2 vWD. However, vWF:CBA of the reclassified dogs was not persistently abnormal, a finding compatible with acquired type 2 vWD. Some Doberman Pinschers had lower antigen-to-activity ratios than other breeds with type 1 vWD, suggesting that Doberman Pinschers have more functional circulating vWF. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of canine vWF activity should be included among the vWF-specific assays used to confirm type 2 vWD. The prevalence of inherited forms of type 2 vWD in screened dogs is lower than acquired forms that can result secondary to underlying disease.     

An interobserver and intraobserver study of buccal mucosal bleeding time in Greyhounds

Two observers experienced with the buccal mucosal bleeding-time technique using a standardised device (Surgicutt) performed the test on 20 Greyhounds, to evaluate interobserver and intraobserver repeatability. The interobserver and intraobserver repeatability were both about 2 minutes. The results indicated that, for any two readings within a dog, the buccal mucosal bleeding time may differ by up to +/- 2 minutes. A single reading was accurate to within +/- 80 seconds. Sixty-one Greyhounds were used to establish a reference interval for the buccal mucosal bleeding time, and to assess the relationship between the buccal mucosal bleeding time and plasma von Willebrand factor concentration. The mean was 129.5 (SD 44.2) seconds. The reference interval was 53 to 235 seconds, which was slightly lower than non-greyhounds. No significant correlation (r=-0. 18, P=0.17) between the buccal mucosal bleeding time and plasma von Willebrand factor concentration was found in the 61 Greyhounds, where plasma von Willebrand factor concentration was in the range 29 to 160 Canine Units dL(-1).     

Paraparesis caused by epidural granuloma in a cat

Caudal paraparesis in a cat was determined to be caused by an epidural mass. Surgical decompression was performed, and the mass was determined to be a granuloma. Fusobacterium and Bacteroides spp were isolated from the granuloma. Epidural granulomas are seldom reported in dogs and cats. Decompression and administration of antibiotics led to recovery of this cat even though in human beings an unfavorable prognosis is given if neurologic deficits have developed.     

Use of a questionnaire to predict von Willebrand disease status and characterize hemorrhagic signs in a population of dogs and evaluation of a diagnostic profile to predict risk of bleeding

The objective of this study was to use a questionnaire 1) for characterization of hemorrhagic signs; 2) to assess its value as a predictor of von Willebrand Disease (vWD) status; and 3) for evaluation of the vWD diagnostic profile [platelet function analysis using the PFA-100, Collagen binding assay (vWF:CBA), and vWF antigen ELISA (vWF:Ag)], partial thromboplastin time (PTT) and Factor VIII activity (FVIII) as predictors of hemorrhagic risk. von Willebrand factor (vWF) concentration and function was assessed for each of the 165 canine participants using the vWD diagnostic profile. Hemorrhagic signs for each dog were obtained using a standardized questionnaire. Questionnaires were scored according to a previously prepared scoring key. Of the 165 dogs in the study, 43.6% had a low vWF concentration, with only 48.6% of dogs in this group having reports of hemorrhagic signs. Oral bleeding was the most commonly reported sign. The questionnaire had a sensitivity of 48.6% and a specificity of 78.5% for the prediction of vWD status. Using the Spearman correlation coefficient, a statistical association was found between the questionnaire and the vWD diagnostic profile components. However, this could not be translated into an ability to predict hemorrhage. The questionnaire allowed characterization of hemorrhagic signs in a large population of dogs over a range of vWF:Ag concentrations, and demonstrated that the vWD diagnostic profile was unsuccessful in the prediction of hemorrhagic risk. Although the sensitivity was insufficient for a screening tool, the questionnaire did have some discriminatory power in the prediction of vWD status.     

Malignant fibrous histiocytoma in a cat

A large proliferative soft tissue mass found on the forelimb of an adult cat was identified as a malignant fibrous histiocytoma through cytologic and histologic examinations. This is a rare tumor of mesenchymal cell origin, which has been previously reported in cats, dogs, horses, and human beings. In this cat metastasis to the local lymph node was found.