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.     

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.     

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.     

Hemorrhage from the cosmetic otoplasty of Doberman Pinschers with von Willebrand's disease

The hemorrhagic tendencies of 23 Doberman Pinscher pups were observed during cosmetic otoplasty and were ranked by a +1 to +4 grading system (+1 = least hemorrhage, and +4 = most hemorrhage). A second estimate of the hemostatic competencies of these dogs was made by counting the gauze sponges used in the otoplasties. Factor VIII-related antigen concentrations and coagglutinin cofactor concentrations were measured in plasma samples from blood drawn not more than 30 hours before the surgical procedures were done. The factor VIII-related antigen concentrations were between 9% and 147% of the concentration in a normal plasma pool, and the coagglutinin cofactor concentrations were between 1% and 165%, indicating that some of these dogs had von Willebrand's disease. The hemorrhagic tendencies of 12 pups were graded +1. This group had a mean antigen concentration of 75% (min-max, 38% to 147%) and a mean coagglutinin cofactor concentration of 89% (min-max, 42% to 165%). These were significantly greater than the antigen and cofactor concentrations of the grades +2 (n = 5), +3 (n = 3), or +4 (n = 3) dogs. Significant differences were not found when antigen concentrations of the grade +2 dogs (mean, 16%; min-max, 11% to 22%), grade +3 dogs (mean, 13%; 12% to 16%), and grade +4 dogs (mean, 11%; 9% to 12%) were compared with each other, nor were significant differences seen among the coagglutinin cofactor concentrations of the grade +2 dogs (mean, 7%; min-max, 1% to 11%), grade +3 dogs (mean, 6%, 4% to 8%), and grade +4 dogs (mean, 5%; 2% to 9%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Craniomandibular osteopathy in Doberman Pinschers

Two young Doberman Pinschers with painless, firm enlargement of the mandibles were investigated. Craniomandibular osteopathy was diagnosed in each case on the basis of characteristic radiographic and gross and microscopic lesions.     

Signal-Averaged Electrocardiograms in Normal Doberman Pinschers

Signal-averaged electrocardiograms (SAECGs) were performed on nonsedated normal dogs in left-lateral recumbency. Following signal averaging, both time-domain and 3-dimensional frequency-domain analyses were performed. For time-domain analysis, the high-frequency QRS (HFQRS) duration, duration of the terminal QRS complex less than 40 μV (LAS₄₀), and root mean square (RMS) voltages (μV) of the terminal 40 milliseconds (RMS₄₀) and 30 milliseconds of the QRS complex were calculated. For frequency-domain analysis, correlation ratios were calculated for 30-, 40-, 50-, and 60-millisecond segment lengths begun 10, 15, or 20 milliseconds before the end of the QRS complex. Spectro-temporal mapping was also performed. All of the parameters of the SAECGs analyzed in the time domain were associated with each other. LAS₄₀ and RMS voltages regressed significantly ( P < .0000) on the HFQRS duration. Ninety-five percent of the HFQRSs were 55–75 milliseconds, 95% of the LAS₄₀ s were 9–26 milliseconds, and 95% of the RMS₄₀ voltages were 177–444 μV. None of the SAECGs contained evidence of ventricular late potentials. Spectro-temporal maps were similar in each dog when the same segment lengths and starting points were compared. No evidence of ventricular late potentials was observed. Correlation ratios were lower when windowed segments included 15 or 20 milliseconds (versus 10 milliseconds) of the terminal QRS complex. When only 10 milliseconds of the terminal QRS complex were included in windowed segments, the mean correlation ratios for 30-and 40-millisecond segment lengths were > 0.8 and > 0.61 in 67% of all analyses, respectively.     

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.     

Assessment of diastolic function by Doppler echocardiography in normal Doberman Pinschers and Doberman Pinschers with dilated cardiomyopathy

BACKGROUND: Assessment of diastolic function in patients with dilated cardiomyopathy (DCM) has the potential to add valuable information regarding hemodynamics, disease severity, and prognosis. The purpose of this study was to determine transmitral flow (TMF), isovolumic relaxation time (IVRT), pulmonary venous flow (PVF), flow propagation velocity (Vp), and mitral annular velocities by tissue Doppler in Doberman Pinschers with and without DCM. HYPOTHESIS: It was anticipated that normal and DCM Dobermans would differ with respect to these parameters, and that associations with time to congestive heart failure (CHF) or death would be found. ANIMALS: Thirty client-owned Doberman Pinschers (10 each of normal, occult DCM, and overt DCM) were studied. METHODS: Each dog underwent echocardiography with or without thoracic radiography (to confirm CHF) for classification as normal or DCM-affected, followed by collection of echocardiographic diastolic parameters. RESULTS: The group with occult DCM exhibited features of pseudonormal TMF, reduced systolic to diastolic PVF ratio, and reduced Vp. Shorter early TMF deceleration time (DTE) was associated with shorter time to CHF or sudden death. The group with overt DCM exhibited restrictive TMF, blunted systolic PVF, and reduced early and late diastolic mitral annular velocities. CONCLUSIONS AND CLINICAL IMPORTANCE: Doberman Pinschers showed evidence of moderate and severe diastolic dysfunction in occult and overt DCM, respectively. Short DTE may be a useful predictor of onset of CHF or sudden death.     

Blanket and flank sucking in Doberman Pinschers

OBJECTIVE: To evaluate blanket and flank sucking and any association with pica in Doberman Pinschers. DESIGN: Survey and case-control study. ANIMALS: 153 Doberman Pinschers (77 dogs with blanket or flank sucking and 76 unaffected dogs). PROCEDURES: Owners of Doberman Pinschers with blanket sucking, flank sucking, or both were surveyed regarding the age of onset, triggers, frequency, duration, interruptability, and associated medical and behavioral consequences. A putative association of blanket sucking and flank sucking with pica was examined by comparison of affected dogs with unaffected dogs. RESULTS: Apart from the difference in the object of oral activity between blanket and flank suckers, age of onset was the only variable that differed between dogs with the 2 conditions. Dogs with blanket or flank sucking had a higher prevalence of pica than the unaffected population. CONCLUSIONS AND CLINICAL RELEVANCE: Blanket and flank sucking are apparently related conditions that can occur with sufficient intensity to cause medical sequelae. These nonnutritive suckling behaviors share similarities with other canine compulsive disorders and are associated with pica. Veterinarians should advise owners that flank and blanket sucking are abnormal, potentially harmful behaviors in dogs. Treatment should be considered for severely affected dogs or when flank or blanket sucking is associated with medical problems.     

Follicular Dysplasia in Adult Black and Red Doberman Pinschers

Abstract— Four black and two red Doberman Pinschers with a slowly progressive, dorsal hypotrichosis were studied. All six dogs developed the hair loss as adults and hypotrichosis was permanent. Skin biopsies showed changes compatible with follicular dysplasia.
Résumé— L'etude porte sur 4 Dobermans noirs et 2 Dobermans marrons présentant une hypotrichose dorsale d'extension progressive. L'hypotrichose dorsale d'extension progressive. L'hypotrichose s'est développée chez les 6 chiens à l'âge adulte et est permanente. Les biopsies cutanées ont montré des images compatibles avec le diagnostic de dysplasie folliculaire.
Zusammenfassung— Bei vier schwarzen und zwei roten Dobermännern wurde eine langsam fortschreitende dorsale Hypotrichose festgestellt. Alle 6 Hunde verloren als adulte Tiere permanent Haare. Die histologischen Untersuchungen zeigten Veränderungen, die einer Follikeldysplasie entsprechen.
Resumen  Se describe la presencia de una hipotricosis dorsal de progresión lenta en cuatro perros de raza Doberman color negro y dos perros de raza Doberman y color rojo. En los seis animales la hipotricosis se inició cuando eran adultos y se mantuvo de forma permanente. Las biopsias cutáneas mostraron cambios histopatológicos compatibles con una displasia folicular.     

Cardiac Troponin I in Doberman Pinschers with Cardiomyopathy

Background: Cardiac troponin I (cTnI) is useful for detection of cardiac myocyte damage, but its efficacy in detecting various stages of dilated cardiomyopathy (DCM) in Doberman Pinschers is unclear. Objectives: To evaluate the diagnostic value of cTnI in various stages of DCM in Dobermans. Animals: Six hundred and fifty‐three cTnI measurements of 336 Doberman Pinschers. Methods: Using a longitudinal study design, staging of the disease was based upon 24‐hour‐ambulatory‐ECG (Holter) and echocardiography. A total of 447 cTnI measurements were performed in 264 healthy Dobermans, and 206 cTnI measurements in 75 Dobermans with cardiomyopathy. Eighty‐eight cTnI samples were from dogs with >100 ventricular premature contractions (VPCs)/24 hour, but without echocardiographic changes (“VPC group”). Additional 19 samples originated from dogs with only echocardiographic changes (“ECHO group”), and 56 samples from dogs with both VPCs and echocardiographic changes (“VPC plus ECHO group”). Twenty samples were from dogs with clinical signs (“clinical group”). The group “incipient” included 23 dogs, that were considered to be normal according to Holter and echocardiography at the time of the exam, but that developed DCM within 1.5 years. Results: cTnI values of dogs in all disease groups, including the “incipient” (0.30 ± 0.20) and “VPC group” (0.36 ± 0.34), were significantly (P= .04, P < .001) higher than the control group (0.07 ± 0.16). A cut‐off value of >0.22 ng/mL had a sensitivity of 79.5% and a specificity of 84.4% to detect all forms of cardiomyopathy. Conclusions and Clinical Importance: cTnI measurement is a valuable diagnostic test that can detect cardiomyopathy in dogs that are otherwise clinically normal.     

Plasma fatty acid concentrations in Boxers and Doberman Pinschers

OBJECTIVE: To compare plasma fatty acid concentrations and the relationships of fatty acids to arrhythmias in Boxers versus Doberman Pinschers. ANIMALS: 38 Boxers and 13 Doberman Pinschers. PROCEDURES: Boxers and Doberman Pinschers evaluated via Holter recording and for which a blood sample was available were included. Echocardiograms were performed in 49 of 51 dogs. The number of ventricular premature complexes (VPCs)/24 h was counted and fatty acids analyzed. Plasma fatty acid concentrations and VPCs/24 h, as well as correlations between the 2 variables, were compared between the 2 breeds. RESULTS: Compared with the Doberman Pinschers, Boxers had significantly higher plasma concentrations of gamma-linolenic acid but lower concentrations of arachidonic acid. Total n-6 fatty acids and total polyunsaturated fatty acid concentrations were higher in Doberman Pinschers. There were significant, but weak, positive correlations between VPCs and oleic acid, total n-3 fatty acids, and total n-9 fatty acids in Boxers but not in Doberman Pinschers. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggested that plasma fatty acid concentrations may differ between Boxers and Doberman Pinschers and that the relationship between fatty acid concentrations and VPCs may be different between these 2 breeds.     

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.     

Plasma big endothelin-1, atrial natriuretic peptide, aldosterone, and norepinephrine concentrations in normal Doberman Pinschers and Doberman Pinschers with dilated cardiomyopathy

BACKGROUND: Dilated cardiomyopathy (DCM) results in progressive myocardial and circulatory dysfunction causing activation of a number of neurohormonal systems, including the endothelin (ET) system, which is only beginning to be described in clinical veterinary medicine. Measurement of these circulating neurohormones possesses potential utility in the diagnosis, staging, and assessment of prognosis in cardiac disease. HYPOTHESIS: We hypothesized that plasma big ET-1, norepinephrine (NE), aldosterone, and atrial natriuretic peptide (ANP) concentrations in normal Dobermans would differ from those in Dobermans with DCM, and that concentrations of these hormones would be associated with time to congestive heart failure (CHF) or death. ANIMALS: Thirty client-owned Dobermans (10 each of normal, occult DCM, and overt DCM) were included in the study. METHODS: Dogs underwent an echocardiogram, ECG, and blood sample collection. Neurohormones were measured by high-pressure liquid chromatography (NE) or commercial assays. RESULTS: Dogs with occult DCM had significantly higher ANP concentrations compared with normal dogs (least squares means [95% confidence interval, CI]: occult female 53.7 pg/mL [40.2-71.7] versus normal female 31.6 pg/mL [24.8-40.3], P = .026; occult male 86.1 pg/mL [64.7-115] versus normal male 12.1 pg/mL [5.1-28.7], P = .011). Dogs with overt DCM had significantly higher concentrations of all neurohormones compared with the normal group. Furthermore, increasing big ET-1 (risk ratio [RR] 2.7, CI 1.3-8.6, P = .01) and NE concentrations (RR 3.9, CI 1.1-18.1, P = .03) over 1 month were associated with a shorter survival time. CONCLUSIONS AND CLINICAL IMPORTANCE: High ANP concentrations can identify dogs with advanced occult DCM. Increasing big ET-1 or NE concentrations over time can be useful predictors of poor prognosis.     

Association between liver copper concentration and subclinical hepatitis in Doberman Pinschers

The prevalence of subclinical hepatitis was investigated in a group of 106 randomly selected 3-year-old Doberman Pinschers. Histopathologic examination of liver samples from 65 dogs (52 dogs with high bile acids, alkaline phosphatase activity, or alanine aminotransferase activity or with copper granules in hepatocytes in a liver aspirate and 13 normal dogs) revealed subclinical hepatitis in 22 dogs (19 females and 3 males). Liver copper concentrations measured by instrumental neutron activation analysis was significantly higher (mean +/- SD; 419 +/- 414 microg/g dry matter) in dogs with hepatitis than those without liver disease (197 +/- 113 microg/g; P = .0008). At 2.6 +/- 0.6 years hepatitis persisted in 5 of 16 dogs available for examination. One dog with a high copper concentration but normal liver subsequently developed subclinical hepatitis after 3 years. During the follow-up period, the average copper concentration of the 6 dogs with persistent subclinical hepatitis was 939 +/- 299 microg/g and had continued to rise significantly (P = .02). The hepatitis in these dogs was associated with apoptotic hepatocytes and copper-laden Kupffer cells in centrolobular regions. The results of this study suggest that there is a relationship among copper storage, hepatocellular damage, and hepatitis in Doberman Pinschers.     

Prevalence of Dilated Cardiomyopathy in Doberman Pinschers in Various Age Groups

Background: Dilated cardiomyopathy (DCM) in Doberman Pinschers is an autosomal dominant inherited disease. The prevalence of DCM in Doberman Pinschers of various age groups in Europe is currently unknown, but this information would be important to develop recommendations for screening programs. Objectives: To evaluate the prevalence of cardiomyopathy in various age groups of Dobermans. Animals: Seven hundred and seventy‐five examinations in 412 Doberman Pinschers. Methods: Dogs were included in a prospective longitudinal cohort study. Each examination included echocardiography and 24‐hour ECG (Holter) examination. A cut‐off value of >100 ventricular premature contractions (VPCs) per 24 hours on Holter examination or abnormal echocardiography was considered diagnostic for cardiomyopathy. The cumulative prevalence included all dogs with DCM and healthy dogs >7 years of age. Results: DCM prevalence in various age groups was as follows: age group 1 (1 to <2 years) 3.3%, age group 2 (2 to <4 years) 9.9%, age group 3 (4 to <6 years) 12.5%, age group 4 (6 to <8 years) 43.6%, and age group 5 (>8 years) 44.1%. The cumulative prevalence of Doberman Pinscher cardiomyopathy was 58.2%. There was an equal sex distribution, but male dogs showed earlier echocardiographic changes than did female dogs, which had significantly more VPCs. Conclusions and Clinical Importance: The prevalence of Doberman cardiomyopathy is very high in Europe. Disease manifestation and progression are different between male and female dogs. Yearly screening for DCM by Holter examination and echocardiography is recommended, starting at 2 years of age.     

Assessment of mechanical ventricular synchrony in Doberman Pinschers with dilated cardiomyopathy

Objectives

Loss of temporal synchrony of myocardial contraction has been shown to reduce systolic function and be responsible for disease progression in people. The objective of this study is the assessment of inter- and intra ventricular synchrony in healthy Doberman Pinschers and those with dilated cardiomyopathy (DCM) by use of conventional Doppler and tissue velocity imaging.

Animals

A total of 60 scans from 35 client-owned Doberman Pinschers presented for cardiac evaluation were analysed.

Methods

Retrospective analysis of data. Using the European Society of Veterinary Cardiology DCM taskforce scoring system, Doberman Pinschers were classified into 4 groups: Control (Group 1; n = 12), depressed systolic function other than DCM (Group 2; n = 9), preclinical DCM (Group 3; n = 8) and symptomatic DCM (Group 4; n = 6). The time intervals between the beginning of the QRS complex and the peak velocity of pulmonic flow (Q-P) and the peak aortic flow (Q-Ao) were used to assess global synchrony between both ventricles. The time intervals between the beginning of the QRS complex and the peak myocardial systolic velocity (Q-peak S) and the onset of myocardial systolic velocity (Q-start S) were measured at the base of the right and left ventricular free wall (RVFW and LVFW) and interventricular septum (IVS), and used to determine segmental longitudinal inter- and intra ventricular synchrony.

Results

No significant loss of global or segmental longitudinal inter- or intra ventricular synchrony was identified between the groups.

Conclusion

Impairment of longitudinal fibre synchrony does not appear to be significantly associated with clinical status of DCM in Doberman Pinschers, although it was identified in certain individuals.