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.     

Effect of desmopressin on von Willebrand factor multimers in Doberman Pinschers with type 1 von Willebrand disease

OBJECTIVE: To assess the effect of desmopressin (DDAVP) administration in Doberman Pinschers with type 1 von Willebrand disease (vWD) on plasma von Willebrand factor (vWF) multimers through determination of vWF collagen binding activity (vWF:CBA; a functional vWF assay dependent on the presence of high-molecular-weight [HMWI multimers), comparison of vWF antigen concentration (vWF:Ag) to vWF:CBA, and vWF multimer size distribution. ANIMALS: 16 Doberman Pinschers with type 1 vWD and 5 clinically normal control dogs. PROCEDURE: Plasma vWF:Ag and vWF:CBA assays and vWF multimer analysis were performed before and 1 hour after administration of DDAVP (1 microg/kg, SC). RESULTS: Following DDAVP administration, dogs with type 1 vWD had an increase in mean baseline values of plasma vWF:Ag and vWF:CBA from 10% to 17% for both variables. The mean vWF Ag:CBA ratio at baseline (0.95) was similar after DDAVP administration (0.97), indicating concordant increases in plasma vWF concentration and activity. In control dogs, mean plasma vWF:Ag and vWF:CBA increased from baseline values of 64% to 113% and 58% to 114%, respectively, and the vWF Ag:CBA ratios were unchanged (1.1 vs 1.0) after DDAVP administration. Plasma vWF multimer analysis revealed proportional increases in band intensity for all multimer sizes following DDAVP administration, in comparison to baseline for the control dogs and Doberman Pinschers with vWD, consistent with vWF Ag:CBA ratios of approximately 1. CONCLUSIONS AND CLINICAL RELEVANCE: Beneficial effects of DDAVP on primary hemostasis in Doberman Pinschers with type 1 vWD cannot be explained by preferential increases in HMW vWF multimers.     

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.     

Effect of desmopressin acetate administration on primary hemostasis in Doberman Pinschers with type-1 von Willebrand disease as assessed by a point-of-care instrument

OBJECTIVE: To evaluate primary hemostasis following administration of desmopressin acetate (DDAVP) to Doberman Pinschers with type-1 von Willebrand disease (vWD). ANIMALS: 16 nonanemic Doberman Pinschers with type-1 vWD. PROCEDURE: Closure time (CT), defined as time required for occlusion of an aperture by a platelet plug assessed within the point-of-care instrument, plasma von Willebrand factor (vWF) concentration, and buccal mucosal bleeding time (BMBT) were determined before and 1 hour after administration of DDAVP (1 microg/kg, SC). RESULTS: Baseline closure times measured with adenosine diphosphate ([ADP-CT], 108 to > 300 seconds; reference range, 52 to 86 seconds) and epinephrine ([EPI-CT], 285 to > 300 seconds; 97 to 225 seconds) as platelet agonists were prolonged in all dogs. Following DDAVP administration, ADP-CT (59 to 186 seconds) was significantly shortened from baseline, but there was no decrease in EPI-CT. Although mean plasma vWF concentration increased significantly after DDAVP administration, only 1 dog had an increase of > 35 U/dL. There was no correlation between increase in plasma vWF concentration and shortening of the ADP-CT. Baseline BMBT was prolonged in 12 of 14 dogs, with significant shortening of BMBT after DDAVP administration in 6 of 7 dogs. In vitro replacement of vWF-deficient plasma with plasma from an unaffected dog shortened the ADP-CT whereas in vitro addition of DDAVP had no effect. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of DDAVP to Doberman Pinschers with type-1 vWD resulted in improved hemostatic function, as assessed by the point-of-care instrument and shortening of BMBT, despite minimal increase in plasma vWF concentration.     

Efficacy of Fresh-Frozen Plasma and Cryoprecipitate in Dogs with von Willebrand's Disease or Hemophilia A

Here we report the comparative efficacy of fresh-frozen plasma (FFP) and Cryoprecipitate in the treatment of 2 inherited bleeding disorders in dogs. The dogs were divided into 3 groups, consisting of 4 Doberman Pinschers with type I von Willebrand's disease (vWD) (group I), 1 Scottish Terrier with type III vWD (group 2), and 4 German Shepherd Dogs with hemophilia A (group 3). In vWD, therapeutic efficacy was determined by the ability of the products to increase von Willebrand factor antigen (vWf:Ag) concentrations above 35 canine units (CU)/dL and to correct the prolonged buccal mucosal bleeding time. Therapeutic efficacy in hemophilia A was assessed by the ability of the products to increase the factor VIII coagulant (FVIII:C) activity above 30 CU/dL. In both groups 1 and 2, higher increases in vWf:Ag were achieved with Cryoprecipitate than with FFP, despite a significantly smaller total amount of vWf:Ag (in CU) being infused with Cryoprecipitate. The maximum vWf:Ag attained after infusion in group 1 was dependent on both the baseline vWf:Ag concentration and on the type of infusion product. The dogs with vWD in both groups also displayed a delayed increase in FVIII:C activity after infusion of both plasma products, which is characteristic of the disease. In group 3, Cryoprecipitate achieved similar increases in FVIII:C activity compared to FFP, although a significantly lesser amount of FVIII:C (in CU) was delivered with Cryoprecipitate. Six of the 9 dogs treated with FFP experienced adverse effects ranging from mild pruritus to pallor and weakness, whereas none of the 9 dogs treated with Cryoprecipitate had any observable adverse reactions ( P = .009). Based on its efficacy and safety, we recommend Cryoprecipitate over FFP for treatment or prophylaxis of hemorrhagic episodes in dogs with vWD or hemophilia A.     

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.     

A von Willebrand's factor genomic nucleotide variant and polymerase chain reaction diagnostic test associated with inheritable type-2 von Willebrand's disease in a line of german shorthaired pointer dogs

Heritable, type-2 von Willebrand's disease (vWD) was studied in a line of German Shorthaired Pointers (GSPs) in which some members had a nucleotide variant in exon 28 of the von Willebrand factor (VWF) gene. A polymerase chain reaction (PCR) diagnostic test for the nucleotide variant was developed to establish the disorder's mode of inheritance and to eliminate it from the line. Thirty-six of the 49 GSPs in the line, 14 unrelated GSP controls, and 71 unrelated dogs of various breeds were tested for the presence of the variant nucleotide. All the dogs with a vWF antigen deficiency (<70% of normal) were either homozygous or heterozygous for the nucleotide variant. The variant was not located in any tested dog in the line or outside of the line with a vWF antigen value greater than 68%. Of the GSPs in the line tested, two were homozygous for the variant, 15 were heterozygous, and 19 were variant free. The collective evidence of this and other studies is consistent with the variant nucleotide being the cause of the type-2 vWD in this line of GSPs and German Wirehaired Pointers. The PCR diagnostic test for the variant nucleotide was successfully used to select and produce progeny that were variant free and vWD free. This test should be effective in the subsequent elimination of this same variant from other lines of dogs.     

von Willebrand's disease in Scottish Terriers in Australia

SUMMARY Over a 5-year period (1988–92), von Willebrand factor antigen (vWf:Ag) assays were performed on plasma samples from 207 Scottish Terriers. Based on these tests, 47 dogs (23%) had vWf:Ag concentrations < 50 canine units (CU)/dL and were classified as heterozygous carriers of the von Willebrand's disease (vWD) gene, while 9 (4%) had concentrations below the sensitivity of the assays and were classified as homozygous. There was thus an overall prevalence of 27% for the vWD gene in the Scottish Terriers tested. The homozygous dogs (median age 0.6 years at diagnosis) consisted of 7 males and 2 females. Eight of these had haemorrhage attributable to the disease, mostly spontaneous and from the oral mucosa. Other signs included haemorrhage induced by trauma or surgery, easy bruising and epistaxis. Many haemorrhagic episodes were severe enough to warrant therapeutic intervention and there was a single fatality. Pedigree analysis, possible in 7 of the dogs, revealed that each was the progeny of a mating between dogs with vWf:Ag concentrations < 50 CU/dL, which supported an autosomal recessive mode of inheritance. A single heterozygous carrier suffered haemorrhage after surgery that, in contrast to the homozygotes, was mild and did not require therapy. The data indicate that vWD is a significant problem in Scottish Terriers in Australia. Accordingly, we recommend that steps be taken to reduce the prevalence of the disease and thereby the number of clinically affected dogs, such as the establishment of a national testing scheme to determine the vWD status of all breeding dogs.     

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.     

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.     

利用PCR-RFLP检测五品种警犬遗传缺陷——血管性假性血友病

犬血管性假性血友病(vWD)是常染色体不完全显性遗传性出血病.血管性假血友病因子(vWF)的数量和质量正常与否决定着是否患有vWD,而vWF基因的表达又控制着vWF的数量和质量.本研究应用DNA测序技术和PCR-RFLP方法检测德国牧羊犬、杜伯文犬、罗威纳犬、史宾格犬和马里努阿犬等5个品种共132头犬的vWF基因5个候选区域.结果显示,德国牧羊犬、罗威纳犬、史宾格犬和马里努阿犬未发现vWF突变基因,杜伯文犬中有2头患病和3头携带者,携带频率为5.16%.     

Clinical and laboratory features of a severe form of von Willebrand disease in Shetland sheepdogs

Ten clinically affected Shetland Sheepdogs were evaluated to define their severe bleeding diathesis and were determined to have von Willebrand factor antigen (vWF:Ag) values less than 0.1% by ELISA assay. The virtual absence of vWF protein by ELISA assay and on multimeric analysis was diagnostic of either homozygosity or probable double heterozygosity for the canine von Willebrand disease (vWD) gene. Clinically affected dogs have type-III vWD and are the offspring of 2 heterozygous parents carrying type-I vWD. Twenty-three percent (1,428 dogs) of the more than 6,000 Shetland Sheepdogs screened for vWD at our facility since 1982 tested within the heterozygous carrier range for the common type-I form of this inherited disorder. Veterinarians and breeders should be aware of the potential for bleeding associated with elective and medical procedures in Shetland Sheepdogs and should use caution when breeding carriers of vWD because of the risk of producing clinically affected offspring with severe type-III vWD.     

The effects of desmopressin on plasma factor VIII/von Willebrand factor activity in dogs with von Willebrand''s disease.

Eight unanesthetized normal dogs and seven dogs with von Willebrand's disease (vWD) were given desmopressin (0.6 micrograms/kg, IV) in order to determine the effects of this drug on plasma Factor VIII/vWF activity. Seven of the normal dogs and four of the vWD dogs were administered an equal volume of saline (control infusion) on another occasion. The other three vWD dogs underwent major surgery after treatment with desmopressin. Plasma FVIII coagulant activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), and FVIII-ristocetin co-factor activity (FVIII:RC) were quantitated before infusion and at 60 minutes postinfusion. Activities were expressed as a percentage of the activity of a pooled canine plasma (12 dogs) arbitrarily designated as having 100% FVIII:C, vWF:Ag, and FVIII:RC activity. Plasma FVIII:C activity increased by 28% in the normal dogs and by 37% in the dogs with vWD. Plasma vWF:Ag increased more than twofold in normal dogs after desmopressin treatment. In the vWD dogs the average increase was also twofold, however there was much greater variability between dogs with increases ranging from 1.2 fold to 2.4 fold. Plasma FVIII:RC activity almost doubled in normal dogs, however like vWF:Ag, the increases in vWD dogs were more variable. One vWD dog had no increase in FVIII:RC while in the remaining six dogs FVIII:RC increases ranged from 1.8 to 2.9 fold. The results of this study indicate that a single intravenous dose of desmopressin (0.6 micrograms/kg) causes a significant elevation in plasma vWF:Ag and FVIII:RC activity and a much lesser increase in FVIII:C activity in normal unanesthetized dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

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.     

Evaluation of laboratory methods to improve characterization of dogs with von Willebrand disease

The objective of the study was to investigate the value of additional tests [platelet count, partial thromboplastin time (PTT), platelet function analysis using the PFA-100, Collagen binding assay (vWF:CBA), and Factor VIII activity], for use in conjunction with the von Willebrand factor antigen enzyme-linked immunosorbent assay (ELISA), as part of a newly developed diagnostic profile for improved characterization of patients with von Willebrand disease (vWD). The study population included 183 clinically healthy canines ranging in vWF:Ag concentration from 1% to 125%. The Asserachrom vWF:Ag ELISA assay was used as an external control for the determination of vWD status. Degree of association between the additional tests and vWF concentration was evaluated, and associations between the additional tests were also assessed, including their ability to distinguish dogs with vWD from those without vWD. In addition, a reference interval was determined for the PFA-100 platelet function analyzer. Strong associations were found between the PFA-100, vWF:CBA, and Asserachrom vWF:Ag assay, and a significant association was found between the PFA-100 and vWF:CBA. An association was detected between Factor VIII activity and the Asserachrom vWF:Ag assay, the vWF:CBA and the PFA-100; however, a corresponding pattern was not visually apparent in the raw data, making the association clinically irrelevant. The association between the platelet count and the PTT with the other additional tests was negligible. Based on our results, the vWF:CBA and PFA-100 would be valuable assets, in conjunction with a vWF:Ag assay, in a canine vWD diagnostic profile to further characterize patients with this disease.     

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.     

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.     

Effect of levothyroxine administration on hemostatic analytes in Doberman Pinschers with von Willebrand disease

Levothyroxine administration has been suggested to be an effective treatment for canine von Willebrand disease (vWd), but evidence supporting this treatment is lacking. Effects of levothyroxine administration were evaluated in 8 euthyroid Doberman Pinschers with plasma von Willebrand factor (vWf) concentrations < 15%, characteristic of type 1 vWd. Levothyroxine (0.04 mg/kg PO q12h) and placebo were administered for 30 days in a 2-period, 2-treatment, double-blinded, crossover design with a 30-day washout period between treatments. Buccal mucosal bleeding time (BMBT), plasma vWf concentration (vWf: Ag), vWf collagen binding activity (vWf:CBA), factor VIII coagulant activity (FVIII:C), and serum concentrations of total thyroxine (T4), free thyroxine (fT4), 3,5,3'-triiodothyronine (T3), and thyroid-stimulating hormone (TSH) were measured on days 0, 2, and 30 of each treatment period. The 8 dogs (1 male, 7 females) had markedly low plasma vWf:Ag (mean, 8.9%; reference range, 70-180%) and vWf:CBA (mean, 11.1%; reference range, >70%). Response to placebo versus levothyroxine treatment was not significantly different between groups at day 0, 2, or 30 for BMBT, vWf:Ag, vWf:CBA, and FVIII:C. Serum T4, fT4, and T3 concentrations were significantly higher and serum TSH significantly lower in the levothyroxine-treated group than in the placebo group at days 2 and 30. Administration of levothyroxine at 0.04 mg/kg caused laboratory evidence of hyperthyroidism but did not affect plasma FVIII:C and vWf:Ag concentrations or vWf-dependent collagen binding and BMBT. The results of this study failed to identify a direct action of levothyroxine supplementation on plasma vWf concentration or activity in euthyroid Doberman Pinschers with vWd.