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1.
Clinical studies have shown that Cavalier King Charles Spaniels (CKCS) have a high prevalence of mitral valvular insufficiency (MVI). Echocardiography has the potential to disclose early valvular changes, and the present prospective study was designed to investigate the occurrence of mitral valve prolapse (MVP) in young CKCS without heart murmurs, and to correlate the degree of MVP with the clinical status of the dogs by including CKCS with MVI as well. The study was based on blinded evaluations of echocardiographic recordings of mitral valves from 34 CKCS and 30 control dogs. Thirteen (87%) of 15 three-year-old CKCS without heart murmurs had MVP (2 total and 11 partial), as compared with 1 (7%) of 15 three-year-old normal Beagle dogs (P < 0.0001), and none of 15 three-year-old normal Medium Size Poodles (P < 0.0001). Of 19 CKCS with MVI, MVP was found in 84% of the entire group and in 100% of dogs with pulmonary congestion or edema. The occurrence of total MVP tended to be higher in the group with MVI (47%, 9/19), when compared with the younger CKCS without heart murmurs (13%, 2/15, P = 0.06). MVP was positively associated with excessive heart rate variability (P = 0.003). The radius of curvature of the anterior mitral valve leaflet in systole was significantly reduced in dogs with MVP when compared with those without (P < 0.0001). In conclusion, this study shows that CKCS at an early age have a high occurrence of MVP. This suggests: 1) A genetic predisposition of CKCS to MVP; and 2) That MVP is a pathogenetic factor in the development of mitral valvular insufficiency. Follow up studies may add further support to these proposals, and clarify whether echocardiography may be an aid in selecting CKCS for future breeding.  相似文献   

2.
The purpose of this prospective study was to investigate platelet function using in vitro tests based on both high and low shear rates and von Willebrand factor (vWf) multimeric composition in dogs with cardiac disease and turbulent high-velocity blood flow. Client-owned asymptomatic, untreated dogs were divided into 4 groups: 14 Cavalier King Charles Spaniels (Cavaliers) with mitral valve prolapse (MVP) and no or minimal mitral regurgitation (MR), 17 Cavaliers with MVP and moderate to severe MR, 14 control dogs, and 10 dogs with subaortic stenosis (SAS). Clinical examinations and echocardiography were performed in all dogs. PFA100 closure times (the ability of platelets to occlude a hole in a membrane at high shear rates), platelet activation markers (plasma thromboxane B2 concentration, platelet surface P-selectin expression), platelet aggregation (in whole blood and platelet-rich plasma with 3 different agonists), and vWf multimers were analyzed. Cavaliers with moderate to severe MR and dogs with SAS had longer closure times and a lower percentage of the largest vWf multimers than did controls. Maximal aggregation responses were unchanged in dogs with SAS but enhanced in Cavaliers with MVP (regardless of MR status) compared with control dogs. No significant difference in platelet activation markers was found among groups. The data suggest that a form of platelet dysfunction detected at high shear rates was present in dogs with MR and SAS, possibly associated with a qualitative vWf defect. Aggregation results suggest increased platelet reactivity in Cavaliers, but the platelets did not appear to circulate in a preactivated state in either disease.  相似文献   

3.
Cavalier King Charles Spaniels (CKCS) often have idiopathic asymptomatic thrombocytopenia. In affected dogs, the thrombocytes often are large, and it has been speculated that the condition could be an inherited macrothrombocytopenia. The aim of this study was to examine the inheritance of idiopathic, asymptomatic thrombocytopenia in CKCS. Sixteen families (both parents and > or = 3 offspring) of privately owned CKCS were included. There were 105 clinically healthy dogs (50 from Denmark and 55 from Sweden): 81 offspring and 26 parents (2 dogs had both roles). Because autoanalyzers have difficulty counting large platelets, the platelets were counted manually, with a counting chamber. Platelet counts were not influenced by age, gender, or heart murmur status. Thrombocytopenia (< or = 100,000 platelets/microL) was found in 46% of the parents. The pedigrees indicated that thrombocytopenia segregated as an autosomal recessive trait and that 100,000 platelets/microL was appropriate as a lower limit of normal. Affected offspring were found in all families, showing that all of the included parents were at least carriers. Therefore, the expected segregation ratios (which were in good accordance with the observed ones) were 1:0, 1:1, and 1:3 for the 3 crosses: affected x affected, normal x affected, and normal x normal. Within a given cross, the mean parental platelet count had no influence on the platelet counts of the offspring. We conclude that idiopathic, asymptomatic thrombocytopenia in CKCS is inherited in an autosomal recessive manner. The condition most likely constitutes an inherited macrothrombocytopenia in dogs.  相似文献   

4.
Platelet counts were performed in 43 Cavalier King Charles Spaniels (CKCS, a breed predisposed to macrothrombocytopenia) and in 10 control dogs using 3 automated systems and 3 manual methods (erythrocyte-lysing agents + counting chamber or evaluation of blood smear). Good correlations were found between platelet counts using all methods (all P < 0.0001; R2 = 0.71-0.85). Best correlations were found between the manual methods. Significantly larger platelets were found in CKCS with platelet count < or = 100,000/microl when compared with control dogs and CKCS with platelet count > 100,000/microl (both P < 0.0001). All platelet counts--except when made with the 2 counting chamber methods--were underestimated at platelet counts < or = 100,000/microl.  相似文献   

5.
Natriuretic peptides are useful in diagnosing heart failure in dogs. However, their usefulness in detecting early stages of myxomatous mitral valve disease (MMVD) has been debated. This study evaluated N-terminal (NT) fragment pro-atrial natriuretic peptide (NT-proANP) and NT-pro-brain natriuretic peptide (NT-proBNP) in 39 Cavalier King Charles Spaniels (CKCS) with pre-clinical mitral valve regurgitation (MR), sixteen dogs with clinical signs of heart failure (HF) and thirteen healthy control dogs. Twenty seven CKCS and ten control dogs were re-examined 4 years after the initial examination and the status of the dogs 5 years after the initial examination was determined by telephone calls to the owner. All dogs were evaluated by clinical examination and echocardiography. CKCS with severe MR had higher NT-proANP and NT-proBNP compared to controls and CKCS with less severe MR. Dogs with clinical signs of HF had markedly elevated NT-proANP and NT-proBNP. Plasma concentrations of the natriuretic peptides measured at re-examination could predict progression in regurgitant jet size.  相似文献   

6.
Background: Increased serotonin (5HT) signaling has been implicated in valvular disease of humans and animals, including canine degenerative mitral valve disease (DMVD). High circulating 5HT concentration is a potential source of increased signaling, and serum 5HT concentrations have not been previously reported in dogs with DMVD.
Hypothesis: Dogs with DMVD and small breed dogs predisposed to DMVD have higher serum 5HT concentrations than large breed controls.
Animals: Fifty dogs affected with DMVD, 34 dogs predisposed to DMVD but without cardiac murmur or echocardiographic evidence of DMVD, and 36 healthy large breed control dogs.
Methods: Prospective analysis. Serum 5HT concentration was measured by an ELISA test.
Results: Median serum 5HT concentration was significantly higher in dogs with DMVD and in dogs predisposed to DMVD as compared with controls (DMVD, 765.5 ng/mL [interquartile range, 561.3–944.4]; predisposed, 774.9 ng/mL [528.3–1,026]; control, 509.8 ng/mL [320.8–708.8]; P = .0001). Subgroup analysis of predisposed dogs indicated significantly higher serum 5HT concentrations in Cavalier King Charles Spaniel (CKCS) dogs than in other breeds (CKCS, 855.0 ng/mL [635.8–1,088]; non-CKCS, 554.2 ng/mL [380.6–648.4]; P = .0023). Age, platelet count, and platelet morphology were not correlated with 5HT concentration in any group.
Conclusions and Clinical Importance: Dogs with DMVD had significantly higher serum 5HT concentrations when compared with large breed control dogs. Healthy CKCS dogs had significantly higher serum 5HT concentrations than other healthy dogs predisposed to DMVD. Additional investigation into a possible role of 5HT in the pathogenesis of DMVD is warranted.  相似文献   

7.
Background: Few reported studies describe normal values from 24‐hour ECG (Holter) recordings of small breed dogs. Objectives: To investigate influence of breed, age, sex, body weight, degree of recording artifact, and mitral valve prolapse (MVP) on Holter recordings of 3 breeds of small dogs that have differing predispositions for myxomatous mitral valve disease. The study also assessed if heart rate (HR) at clinical examination (HRex) was associated with HR during Holter monitoring and evaluated the reproducibility of Holter variables. Animals: Fifty clinically healthy, privately owned dogs of the breeds Cavalier King Charles Spaniel (CKCS), Wire‐haired Dachshund (wD), or Cairn Terrier (CT). Methods: Prospective, longitudinal observational study. Dogs were recruited for clinical examination, echocardiography, and Holter monitoring. In 8 CKCS, Holter recordings were performed twice with a 7‐day interval. Arrhythmia and heart rate variability (HRV) analysis (time and frequency domain analysis) were performed on Holter recordings. Results: Fifteen out of 27 Holter derived variables were significantly associated with breed (P < .03), but not with age (P > .7), sex (P > .2), body weight (P > .7), degree of recording artifact (P > .4), or MVP (P > .6). During Holter recording, minimum (P= .0001) and mean HR (P= .0001) were higher in CKCS compared with wD. CKCS had significantly lower values than wD, CT, or both in 10 out of 13 HRV variables (P < .03). Minimum and mean HR during Holter recording were correlated with HRex (r= 0.55, P= .0003). HR and time domain variables had a coefficient of variation <10%. Conclusions and Clinical Importance: There is an influence of breed on Holter‐derived variables in 3 breeds of small dogs. Arrhythmia and HRV analysis can be performed on 24‐hour ambulatory ECG (Holter) recordings. Arrhythmia analysis includes HR measurements and identification of arrhythmias.  相似文献   

8.
BACKGROUND: Clinical studies investigating platelet function in dogs have had conflicting results that may be caused by normal physiologic variation in platelet response to agonists. OBJECTIVES: The objective of this study was to investigate platelet function in clinically healthy dogs of 4 different breeds by whole-blood aggregometry and with a point-of-care platelet function analyzer (PFA-100), and to evaluate the effect of acetylsalicylic acid (ASA) administration on the results from both methods. METHODS: Forty-five clinically healthy dogs (12 Cavalier King Charles Spaniels [CKCS], 12 Cairn Terriers, 10 Boxers, and 11 Labrador Retrievers) were included in the study. Platelet function was assessed by whole-blood aggregation with ADP (1, 5, 10, and 20 microM) as agonist and by PFA-100 using collagen and epinephrine (Col + Epi) and Col + ADP as agonists. Plasma thromboxane B(2) concentration was determined by an enzyme immunoassay. To investigate the effect of ASA, 10 dogs were dosed daily (75 or 250 mg ASA orally) for 4 consecutive days. RESULTS: A higher platelet aggregation response was found in CKCS compared to the other breeds. Longer PFA-100 closure time (Col + Epi) was found in Cairn Terriers compared to Boxers. Plasma thromboxane B(2) concentration was not statistically different between groups. Administration of ASA prolonged the PFA-100 closure times, using Col + Epi (but not Col + ADP) as agonists. Furthermore, ASA resulted in a decrease in whole-blood platelet aggregation. CONCLUSIONS: Platelet function is influenced by breed, depending upon the methodology applied. However, the importance of these breed differences remains to be investigated. The PFA-100 method with Col + Epi as agonists, and ADP-induced platelet aggregation appear to be sensitive to ASA in dogs.  相似文献   

9.
With aggregometry, increased platelet activity has been reported in Cavalier King Charles Spaniels (CKCS) without mitral regurgitation (MR). In contrast, dogs with MR have been found to have decreased platelet activity. The purpose of this study was to test an easy bedside test of platelet function (the Platelet Function Analyzer [PFA-100]) to see if it could detect an increase in platelet activity in CKCS without MR and a decrease in platelet activity in CKCS with MR. This study included 101 clinically healthy dogs > 1 year of age: 15 control dogs of different breeds and 86 CKCS. None of the dogs received medication or had a history of bleeding. The PFA-100 evaluates platelet function in anticoagulated whole blood under high shear stress. Results are given as closure times (CT): the time it takes before a platelet plug occludes a hole in a membrane coated by agonists. The CT with collagen and adenosine-diphosphate as agonists was similar in control dogs (median 62 seconds; interquartile interval 55-66 seconds) and CKCS with no or minimal MR (55; 52-64 seconds). The CT was higher in CKCS with mild MR (regurgitant jet occupying 15-50% of the left atrial area) (75; 60-84 seconds; P = .0007) and in CKCS with moderate to severe MR (jet > 50%) (87: 66-102 seconds; P < .0001). CKCS with mild, moderate, and severe, clinically inapparent MR have decreased platelet function. The previous finding of increased platelet reactivity in nonthrombocytopenic CKCS without MR could not be reproduced with the PFA-100 device.  相似文献   

10.
The effect of antiplatelet antibody on in vitro platelet function was investigated in 15 dogs with immune-mediated thrombocytopenia (ITP). Platelet aggregation was assessed after addition of serum from healthy dogs (n = 5) or dogs with ITP (n = 15) to platelet-rich plasma from a healthy donor dog. The aggregation responses to adenosine diphosphate, thrombin, and collagen/epinephrine were measured as the maximum aggregation observed after 2 minutes. In 13 of 15 dogs with ITP, maximal aggregation was significantly inhibited in response to ADP, thrombin, or collagen/epinephrine. The slope of the aggregation curve was decreased after addition of serum from 9 of 15 patients. A polyclonal rabbit anti—dog platelet antiserum induced inhibition of aggregation with all 3 agonists.
Serum from control dogs neither inhibited nor activated platelet aggregation. Aggregation experiments were repeated with all 3 agonists after addition of patient immunoglobulin (lg)G or IgG from a healthy dog to platelet-rich plasma. The IgG fraction from 9 of 10 dogs with ITP suppressed platelet aggregation. The IgG fraction from polyclonal rabbit anti—dog platelet antiserum inhibited platelet aggregation with all agonists. These results suggest that many canine ITP patients have circulating antibodies that, in addition to causing platelet destruction, may cause platelet dysfunction.  相似文献   

11.
Background: Many Cavalier King Charles Spaniel (CKCS) dogs are affected by an autosomal recessive dysplasia of platelets resulting in fewer but larger platelets. The IDEXX Vet Autoread (QBC) hematology analyzer directly measures the relative volume of platelets in a blood sample (plateletcrit). We hypothesized that CKCS both with and without hereditary macrothrombocytosis would have a normal plateletcrit and that the QBC results would better identify the total circulating volume of platelets in CKSC than methods directly enumerating platelet numbers.
Objectives: The major purpose of this study was to compare the QBC platelet results with platelet counts from other automated and manual methods for evaluating platelet status in CKCS dogs.
Methods: Platelet counts were determined in fresh EDTA blood from 27 adult CKCS dogs using the QBC, Sysmex XT-2000iV (optical and impedance), CELL-DYN 3500, blood smear estimate, and manual methods. Sysmex optical platelet counts were reanalyzed following gating to determine the number and percentage of normal- and large-sized platelets in each blood sample.
Results: None of the 27 CKCS dogs had thrombocytopenia (defined as <164 × 109 platelets/L) based on the QBC platelet count. Fourteen (52%) to 18 (66%) of the dogs had thrombocytopenia with other methods. The percentage of large platelets, as determined by regating the Sysmex optical platelet counts, ranged from 1% to 75%, in a gradual continuum.
Conclusions: The QBC may be the best analyzer for assessing clinically relevant thrombocytopenia in CKCS dogs, because its platelet count is based on the plateletcrit, a measurement of platelet mass.  相似文献   

12.
Endothelium-dependent (nitric oxide [NO]-mediated) vasodilation is impaired in humans with heart failure. This dysfunction is an important therapeutic target. The plasma concentration of the NO metabolites nitrate and nitrite (collectively referred to as NOx) is a measure of whole-body NO production, provided that the dietary intake of the ions is low. Fifty clinically healthy dogs older than I year (median 5.0 years; interquartile interval 2.6-8.2 years) were studied, including 9 controls of various breeds, 23 Cavalier King Charles Spaniels (CKCSs) with no or minimal mitral regurgitation (MR), 9 CKCSs with mild MR (regurgitant jet occupying 15-50% of the left atrial area), and 9 CKCS with moderate to severe MR (jet >50%) due to myxomatous valve disease. None of the dogs received medication. The dogs were given NOx-free water and a diet with a low concentration of NOx for 96 hours before blood sampling. Multiple linear regression analysis revealed that dog group, but not gender, age, serum creatinine concentration, and platelet count, was associated with NOx concentrations. Control dogs had the same NOx concentration (median 20.0 microM; interquartile interval 15.1-25.5 microM) as CKCSs without MR (median 18.7 microM; interquartile interval 15.5-25.9 microM). Compared to CKCSs without MR, the NOx concentration was lower in CKCSs with mild (median 12.9 microM; interquartile interval 11.0-13.5 microM; P = .04) and moderate to severe (median 11.2 microM; interquartile interval 6.9-17.1 microM; P = .02) MR. In conclusion, CKCSs with mild to severe, clinically silent MR have decreased plasma NOx concentrations, suggesting that endothelial dysfunction develops early in the course of developing MR in dogs.  相似文献   

13.
Cytokines have been associated with the progression of congestive heart failure (CHF) in humans and may be implicated in the pathophysiology of myxomatous mitral valve disease (MMVD) in dogs. The aim of this study was to determine the serum concentrations of cytokines in dogs with MMVD. The study included 16 Cairn terriers with no or minimal mitral regurgitation (MR), 41 Cavalier King Charles Spaniels (CKCS) with different degrees of MR and 11 dogs of different breeds with CHF due to MMVD. Granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, keratinocyte-derived chemokine, interferon-γ-induced protein and monocyte chemoattractant protein-1 (MCP-1) were measured using a canine-specific multiplex immunoassay. CHF dogs had significantly higher MCP-1 concentrations than dogs with no or minimal MR. Among the CKCS, IL-2 and IL-7 decreased with increasing left atrial size and IL-7 also decreased with increasing MR. IL-8 decreased with increasing left ventricular end-systolic internal dimensions. MCP-1 was increased in CHF dogs compared to healthy control dogs and IL-2, IL-7 and IL-8 decreased with increasing indices of disease severity. The results suggest a role for these cytokines in canine MMVD and CHF.  相似文献   

14.
Using the Born method, based on light transmission in platelet rich plasma, the minimum effective concentration (threshold values) of several platelet agonists for inducing maximum platelet aggregation was determined in healthy dogs. The final concentrations of aggregation agonists were as follows: adenosine diphosphate (ADP) (0.5-50 micromol/L; n = 75 healthy dogs), collagen (0.5-20 mg/mL; n = 75), thrombin (0.1-5 IU/mL; n = 75), ristocetin (1-10 mg/mL; n = 10), and epinephrine (5-50 micromol/L; n = 10). Reference values for maximum aggregation with a lower limit of > 80% were achieved for agonist concentrations 25 micromol/L ADP (80-98%), > or = 10 microg/mL collagen (80-96%), and > or = 1 IU/mL thrombin (80-97%). None of the concentrations of epinephrine and ristocetin used in this study induced quantitative aggregation in the whole group of healthy dogs. We also studied platelet aggregation in 14 uraemic dogs using selected concentrations of aggregation agonists. Aggregation was significantly decreased in uraemic dogs using intermediate agonist concentrations, i.e., in the region of the threshold concentration. In contrast, maximum aggregation was increased in uraemic patients compared to reference values using low concentrations of all three agonists (ADP: 1 micromol/L, collagen: 1 microg/mL, and thrombin: 0.1, 0.2 IU/mL).  相似文献   

15.
One hundred ninety consecutive Dachshunds >2 years of age, including 18 families consisting of both parents and 4 or more offspring, were examined clinically and echocardiographically to study the epidemiology and inheritance of mitral valve prolapse (MVP) and other signs of myxomatous mitral valve disease in the dog. From video-recorded echocardiograms, MVP severity, jet size (color Doppler), and leaflet thickness were assessed. With regard to murmur intensity and each of these 3 echocardiographic measurements. the inheritance and the influence of age, gender, coat type, body weight, degree of obesity, heart rate, and thorax dimensions were evaluated. MVP severity correlated positively with age (P < .0001) and heart rate (P = .002), negatively with thorax circumference (P = .0005), and was related to coat type (P = .006). MVP severity progressed faster in males than in females (P = .0002). The other measures of disease severity (jet size, leaflet thickness, and murmur intensity) also correlated positively with age (all P < .0001). When compared in pairs, all 4 measures of disease severity correlated significantly with one other. Pedigree analyses did not disclose agreement with simple Mendelian models, but high disease prevalence made interpretation difficult. Mean parental MVP severity correlated significantly with MVP severity in the offspring (P = .03). The epidemiology of MVP in Dachshunds resembles that of MVP in humans, MVP severity correlates significantly with other measures of the degree of myxomatous mitral valve disease, and MVP is an inherited condition in Dachshunds. A polygenic mode of inheritance is suggested.  相似文献   

16.
The aim of this study was to evaluate platelet function in Dachshunds during early stages of myxomatous mitral valve disease.Clinical examination and echocardiography were performed in 34 wirehaired standard sized Dachshunds. Platelet function was evaluated using the PFA-100 (reported as closure time). In addition, whole blood platelet aggregation response and hemostatic markers were evaluated.Significant longer PFA-100 closure time (CT) was found in 12 Dachshunds with mild mitral regurgitation (MR) compared to 22 Dachshunds with minimal MR. Only five Dachshunds responded to adenosine diphosphate in the whole blood aggregation analyses. There were no differences between the two dog groups in plasma fibrinogen, plasma von Willebrand factor (vWf) or vWf multimer distribution; however, there was a significant correlation between CT and plasma vWf concentration and CT and plasma fibrinogen concentration.The higher CT found in Dachshunds with mild MR suggests a form of platelet dysfunction in Dachshunds with MR.  相似文献   

17.
The Cavalier King Charles Spaniel (CKCS) is prone to severe early onset mitral valve disease. In this study, 36 purebred CKCS dogs were evaluated for mitral valve murmur and divided into early and late onset groups. A genome-wide genetic approach was used to assess whether the condition is determined by a small number of genetic factors. There were no regions of highly discrepant homo/heterozygosity in the two groups. Similarly, there was no evidence for loci associated with mitral valve murmur in a genome-wide association study. This analysis suggests that familial occurrence of mitral valve murmur in the CKCS breed is not due to a single major gene effect, indicating that breeding strategies to eliminate the disease cannot be based on genotype information at this time.  相似文献   

18.
ObjectivesSerotonin has been implicated in canine myxomatous mitral valve disease (MMVD); however, the sources of serotonin have not been fully elucidated. This study compared the concentration of serotonin in plasma and platelets of normal healthy small breed dogs with predisposition to MMVD and dogs with naturally occurring MMVD.Animals43 small-breed client-owned dogs with an approximate weight of <10 kg and age of 6 years or above were divided into 2 groups: a healthy control group (n = 20) and a group with echocardiographic evidence of MMVD (n = 23).Methods5 ml samples of blood were collected. Plasma and platelets were separated by centrifugation and assayed for serotonin measured by enzyme linked immunosorbent assay (ELISA).ResultsMedian plasma serotonin concentration was not significantly different (p = 0.3630) between normal healthy dogs (3.7 ng/ml) and dogs with MMVD (4.3 ng/ml). Males had higher plasma serotonin concentration than females (4.7 and 2.9 ng/ml respectively, p = 0.0043). Platelet serotonin concentration was not different between healthy dogs and dogs with MMVD (128.6 ng/109 platelets and 176.6 ng/109 platelets respectively, p = 0.4575). Age, echocardiographic indices and platelet count showed no correlation with plasma or platelet serotonin concentration.ConclusionsCirculating plasma serotonin is unlikely a major source of serotonin signaling in canine MMVD. Platelets could be a source of serotonin in canine MMVD through platelet adhesion to the mitral valve; however, the amount of serotonin stored in platelets of healthy dogs and dogs with MMVD is not different.  相似文献   

19.
OBJECTIVE: To determine the prevalence of asymptomatic idiopathic macrothrombocytopenia in the population of Cavalier King Charles Spaniels (CKCS) in New South Wales (NSW) and to determine if it exhibits an autosomal recessive inheritance pattern. We also aimed to determine if significant differences existed when counting platelets manually, by auto analyser or by blood smear estimation in CKCS and mixed breed dogs. METHODS: Blood was collected from 172 dogs (152 CKCS and 20 mixed breed) and placed into sodium-citrate anticoagulant. Platelet counts were performed manually, by auto analyser and by blood smear estimates in CKCS and mixed breed dogs. Blood smears were also examined for platelet clumping and erythrocyte, leukocyte and platelet morphology. Pedigree analysis was performed to determine if an autosomal recessive inheritance pattern was supported. RESULTS: A statistically significant difference was found in platelet counts between CKCS and mixed breed dogs (P < 0.0001). CKCS had a platelet count that was 32% that of the controls (95% confidence interval, 28 to 37%). There was no significant difference between methods used to count platelets. Thirty percent of CKCS had macrothrombocytes. Pedigree analysis and examination of obtained and expected segregation ratios from 17 CKCS families supported an autosomal recessive pattern of Mendelian inheritance. CONCLUSIONS: A high prevalence of idiopathic macrothrombocytopenia exists in CKCS in NSW and automated or blood smear estimates are sufficient to count platelet numbers. Data supports an autosomal recessive inheritance pattern.  相似文献   

20.
Background: Cavalier King Charles Spaniels (CKCS) have a high prevalence of inherited macrothrombocytopenia. The purpose of this study was to determine if a mutation in β1-tubulin correlated with presumptive inherited macrothrombocytopenia.
Hypothesis: A mutation in β1-tubulin results in synthesis of an altered β1-tubulin monomer. α-β tubulin dimers within microtubule protofilaments are unstable, resulting in altered megakaryocyte proplatelet formation.
Animals: Blood samples were obtained from CKCS and non-CKCS dogs.
Methods: DNA was used in polymerase chain reaction (PCR) assays to evaluate β1-tubulin . Platelet numbers and mean platelet volume (MPV) were evaluated for a correlation with the presence or absence of a mutation identified in β1-tubulin. Platelets obtained from homozygous, heterozygous, and clear CKCS were further evaluated using electron microscopy and immunofluorescence.
Results: A mutation in the gene encoding β1-tubulin correlated with macrothrombocytopenia in CKCS. Electron microscopy and immunofluorescence studies suggest that platelet microtubules are present but most likely are unstable and decreased in number.
Conclusions and Clinical Importance: The macrothrombocytopenia of CKCS correlated with a mutation in β1-tubulin . α–β tubulin dimers within protofilaments most likely are unstable, leading to altered proplatelet formation by megakaryocytes. This information will aid in distinguishing inherited from acquired thrombocytopenia. It also provides insight into the mechanism of platelet production by megakaryocytes, and also may prove useful in understanding heart-related changes in macrothrombocytopenic CKCS with concurrent mitral valve regurgitation.  相似文献   

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