Red blood cell distribution width in dogs with chronic degenerative valvular disease

Carlo Guglielmini Department of Veterinary Clinical Sciences, University of Teramo, Viale Crispi 212, 64100 Teramo, Italy.

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Helen Poser Department of Animal Medicine, Production, and Health, University of Padova, Viale dell'Università 16, I-35020 Legnaro (PD), Italy.

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Angela Dalla Pria Department of Animal Medicine, Production, and Health, University of Padova, Viale dell'Università 16, I-35020 Legnaro (PD), Italy.

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Michele Drigo Department of Animal Medicine, Production, and Health, University of Padova, Viale dell'Università 16, I-35020 Legnaro (PD), Italy.

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Elisa Mazzotta Department of Animal Medicine, Production, and Health, University of Padova, Viale dell'Università 16, I-35020 Legnaro (PD), Italy.

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Michele Berlanda Department of Animal Medicine, Production, and Health, University of Padova, Viale dell'Università 16, I-35020 Legnaro (PD), Italy.

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Alessia Luciani Department of Veterinary Clinical Sciences, University of Teramo, Viale Crispi 212, 64100 Teramo, Italy.

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Abstract

Objective—To evaluate RBC distribution width (RDW) in dogs with chronic degenerative valvular disease (CDVD) with compensated or decompensated heart failure.

Design—Retrospective case-control study.

Animals—27 healthy dogs and 135 dogs with CDVD (87 dogs with compensated heart failure and 48 dogs with decompensated heart failure).

Procedures—The RDW and various CBC and serum biochemical variables were compared among groups. Correlations between RDW and various echocardiographic variables were evaluated.

Results—Mean ± SD RDW in dogs with CDVD (13.1% ± 1.0%) was not significantly different from that of healthy dogs (12.8% ± 0.8%). The RDW of dogs with CDVD and compensated heart failure (13.0% ± 1.0%) was not significantly different from that of dogs with CDVD and decompensated heart failure (13.2% ± 1.1%). The RDW had a significant, weak, negative correlation with Hct (correlation coefficient, −0.250), hemoglobin concentration (correlation coefficient, −0.219), and mean corpuscular volume (correlation coefficient, −0.211). The RDW had a significant, weak, positive correlation with 1 echocardiographic index of CDVD severity (ie, the left atrium-to-aorta ratio [correlation coefficient, 0.183]).

Conclusions and Clinical Relevance—In this study population, RDW did not seem to be associated with the presence of heart failure or CDVD. (J Am Vet Med Assoc 2013;243:858–862)

Abstract

Objective—To evaluate RBC distribution width (RDW) in dogs with chronic degenerative valvular disease (CDVD) with compensated or decompensated heart failure.

Design—Retrospective case-control study.

Animals—27 healthy dogs and 135 dogs with CDVD (87 dogs with compensated heart failure and 48 dogs with decompensated heart failure).

Procedures—The RDW and various CBC and serum biochemical variables were compared among groups. Correlations between RDW and various echocardiographic variables were evaluated.

Results—Mean ± SD RDW in dogs with CDVD (13.1% ± 1.0%) was not significantly different from that of healthy dogs (12.8% ± 0.8%). The RDW of dogs with CDVD and compensated heart failure (13.0% ± 1.0%) was not significantly different from that of dogs with CDVD and decompensated heart failure (13.2% ± 1.1%). The RDW had a significant, weak, negative correlation with Hct (correlation coefficient, −0.250), hemoglobin concentration (correlation coefficient, −0.219), and mean corpuscular volume (correlation coefficient, −0.211). The RDW had a significant, weak, positive correlation with 1 echocardiographic index of CDVD severity (ie, the left atrium-to-aorta ratio [correlation coefficient, 0.183]).

Conclusions and Clinical Relevance—In this study population, RDW did not seem to be associated with the presence of heart failure or CDVD. (J Am Vet Med Assoc 2013;243:858–862)

Red blood cell distribution width is a quantitative measurement of anisocytosis and reflects the variability in size of the circulating erythrocytes.1,2 Red blood cell distribution width is routinely measured by hematology analyzers and is reported as a component of the CBC. Red blood cell distribution width is typically used to discriminate between regenerative and nonregenerative anemia,1,2 but it has also been associated with other disease processes including liver disease, malnutrition, occult colon cancer, and neoplastic metastases to bone marrow in humans.3 In recent years, considerable attention has been paid to the association between anemia and cardiovascular outcomes in multiple patient populations. Anemia occurs commonly in human patients with chronic heart failure, and a strong relationship exists between anemia and adverse outcomes in heart failure.4–6 The activated pathophysiologic pathways in heart failure induce a cascade of events that ultimately become adverse, including the development of frequent comorbid problems such as cachexia, renal failure, or anemia as part of the cardiorenal anemia syndrome.6 Changes in RDW are associated with cardiovascular and cardiopulmonary diseases, and a strong association has been reported between increasing RDWs and adverse outcomes in human patients with both acute and chronic heart failure and in patients with prior myocardial infarction without symptomatic heart failure.3,7–10 This association is consistently independent of Hgb concentration and persists as one of the strongest overall predictors of morbidity and mortality rate in patients with heart failure, despite adjustments for a broad array of clinical and laboratory variables.3,9

Chronic degenerative valvular disease secondary to myxomatous degeneration is the most common canine cardiac disease, and it is the most common cause of heart failure in dogs.11–13 Chronic degenerative valvular disease and associated mitral regurgitation is typically a slowly progressive disease characterized by cardiac remodeling preceding overt clinical signs of decompensated heart failure.12–14 Furthermore, many affected dogs die for other reasons and do not progress to heart failure.14–16 Different clinical and echocardiographic variables are correlated with survival time in dogs with CDVD.13–17 Among these, the LA:Ao ratio and E-max were found to be significantly associated for all cases of death in multivariate analysis of dogs with CDVD.15,16

Different circulating markers of cardiovascular diseases and heart failure have been investigated in dogs with cardiac disorders, including markers of myocyte injury and stress, markers of cardiac remodeling, markers of endothelial dysfunction, markers of inflammation, neurohormonal markers, and hemostatic biomarkers.18,19 To the best of our knowledge, RDW has never been studied before in dogs with CDVD. Furthermore, few studies have addressed the association between cardiac disease and anemia, including cardiorenal anemia syndrome, in dogs with CDVD. The purpose of the study reported here was to evaluate RDW in dogs with CDVD with or without overt heart failure and to compare it with other laboratory variables and established echocardiographic prognostic indices of the severity of myxomatous valvular degeneration.

Materials and Methods

Criteria for selection of cases and controls—Twenty-seven healthy client-owned dogs admitted for various purposes to the Veterinary Teaching Hospital of the University of Padova from December 2009 to November 2010 were prospectively enrolled as controls. Enrollment was based on written owner consent and results within reference ranges for physical examination, echocardiographic and Doppler echocardiographic examination, CBC including evaluation of the RDW, and serum biochemical profile. Mean ± SD RDW (12.8% ± 0.8%) of the controls was used to calculate the sample size for the case group by use of an open-source commercial software program.20 The parameters used for sample size calculations were as follows: a power of 0.95 (ie, 95%), an α level of 0.05, and a control-to-case ratio of 1 to 5, with a difference to be detected as significant equal to 0.7 (ie, < 1 SD of controls and still within the reference interval for RDW). On the basis of these variables, the program estimated a sample size of 135 dogs with CDVD. Only dogs with CDVD and with an available CBC and serum biochemical profile were included in the study. Diagnosis of CDVD was based on combined clinical (ie, left apical systolic murmur), echocardiographic (ie, thickened, nodular, or prolapsing mitral valve leaflets on 2-D echocardiography), and Doppler echocardiographic (ie, mild to severe mitral valve regurgitation) findings.

Medical records review—Medical records of dogs evaluated at the cardiology service of the Veterinary Teaching Hospital of the University of Teramo and the University of Padova from September 2008 to November 2010 were reviewed.

Procedures—At each center, the same experienced operator (CG or HP) performed the echocardiographic and Doppler echocardiographic examinations in healthy dogs and dogs with CDVD by use of commercial echocardiography.a,b Standard echocardiographic scan planes were used in unsedated dogs.21 Ventricular measurements were obtained from the right parasternal location during 2-D-guided M-mode echocardiography. Measurements of the LA and Ao were obtained with a 2-D method. The spectral Doppler evaluation of transmitral blood flow was obtained from the left apical 4-chamber view. The following echocardiographic and Doppler echocardiographic variables were selected for successive statistical evaluation: LVDd, LVDs, LA, Ao, and E-max. In particular, the following echocardiographic ratio indices were considered: LVDd:Ao, LVDs:Ao, LA:Ao, and FS. According to the ISACHC classification score,22 dogs with CDVD were further subdivided into 2 groups: dogs with compensated (ISACHC class 1a and 1b) and decompensated (ISACHC class 2 and 3) heart failure.

Complete blood count and serum biochemical analyses were performed within 24 hours on blood samples obtained from dogs that were not given food for 12 hours beforehand. The RDW and other hematologic variables were measured by means of automated CBC analyzers.c,d With these instruments, construction of frequency distribution curves of RBC volume became possible and the coefficient of variation of the RBC volume (ie, the RDW) was reported. Serum biochemical variables were evaluated with commercial analyzers.e,f Reference intervals for RDW, Hct, and serum creatinine and urea concentrations, in the laboratories where the analyses were performed, were 11.9% to 14.5%, 38% to 57%, 0.5 to 1.5 mg/dL, and 20 to 50 mg/dL, respectively. Dogs were considered anemic if Hct was ≤ 37%. Dogs were considered to have mild anemia if Hct was ≥ 30% and ≤ 37% and moderate to severe anemia if Hct was ≤ 29%.23 Dogs were considered azotemic if the serum creatinine and urea concentrations were > 1.5 mg/dL and > 50 mg/dL, respectively. Dogs were considered to have prerenal azotemia if they had increased serum urea concentrations without concomitant increased serum creatinine concentrations.24

Statistical analysis—The normality of the data was assessed by means of the 1-sample Kolmogorov-Smirnov nonparametric test. Normally distributed data are reported as mean ± SD values, and non-normally distributed data are reported as median and range values.

One-way ANOVA, followed by Tamhane tests for multiple comparisons, were used to analyze normally distributed continuous data (Hct, Hgb concentration, RDW, mean corpuscular volume, LVDd:Ao ratio, LVDs:Ao ratio, FS, and E-max). For nonnormally distributed data (age; body weight; serum urea, creatinine, and protein concentrations; and LA:Ao ratio), the Kruskal-Wallis nonparametric test was used for comparison among groups, followed by the Mann-Whitney nonparametric test for comparison between groups with a Bonferroni correction for multiple comparisons.

According to normality of data, the Pearson correlation coefficient and the rank correlation by means of the Spearman ρ coefficient were used to assess the degree of association between the RDW and all the variables included in the study (age, body weight, hematologic and serum biochemical variables, and echocardiographic and Doppler echocardiographic indices). All statistical analyses were performed with a statistical software package.g For all comparisons, P < 0.05 was considered significant.

Results

Study population—The study population included 162 dogs of different breeds, with 75 males and 87 females. Of these, 27 dogs were healthy and 135 dogs had CDVD (Table 1). Dogs with CDVD were older and had lower body weights, compared with those of control dogs. The most represented breeds for dogs with CDVD were mixed-breed dogs (n = 68), Dachshunds (7), Yorkshire Terriers (7), Cavalier King Charles Spaniels (6), Miniature Pinschers (5), and German Shepherd Dogs, Italian Hounds, English Setters, and Miniature Poodles (4 each). Other breeds were represented by ≤ 3 dogs each. The most represented breeds for the control group were mixed-breed dogs (n = 9), German Shepherd Dogs (3), and Miniature Pinschers (2).

Table 1—

Demographic data (median [range]) of 27 healthy control dogs and 135 dogs with CDVD.

VariableControlCDVDP value
Age (y)6.0 (2.0–14.0)11.0 (3.0–17.0)< 0.001
Body weight (kg)18.0 (5.0–45.0)10.0 (1.8–43.0)< 0.001
Sex (No. of males/No. of females)12/1573/620.389

Among dogs with CDVD, 64.4% (87/135) had compensated heart failure and 35.6% (48/135) had decompensated heart failure. Anemia was diagnosed in 8.1% (11/135) of dogs with CDVD, and in all cases, anemia was mild. Azotemia was diagnosed in 24.4% (33/135) of dogs with CDVD, and prerenal azotemia was observed in the majority of these dogs (23/33 [69.7%]). Anemia associated with azotemia was found in 3.0% (4/135) of dogs with CDVD.

Laboratory and echocardiographic variables—The mean ± SD Hct of dogs with CDVD and compensated heart failure was significantly (P = 0.01) lower than that of control dogs, but no significant difference was found regarding the Hgb concentration between control dogs and dogs with CDVD and compensated and decompensated heart failure (Table 2). The median serum urea concentration of dogs with CDVD and decompensated heart failure was significantly (P < 0.001) higher than that of control dogs and dogs with CDVD and compensated heart failure. The median serum creatinine concentration of dogs with CDVD and decompensated heart failure was significantly (P = 0.01) higher than that of dogs with CDVD and compensated heart failure. The serum protein concentration of dogs with CDVD and decompensated heart failure was significantly (P < 0.05) lower than that of control dogs and dogs with CDVD and compensated heart failure.

Table 2—

Laboratory and echocardiographic data of 27 healthy control dogs and 135 dogs with CDVD and compensated (n = 87) or decompensated (48) heart failure.

  CDVD 
VariableControlCompensatedDecompensatedOverall P value
Hct (%)49 ± 4.545.4 ± 6.2a47.4 ± 7.50.024
Hgb (g/dL)16.4 ± 1.615.7 ± 2.216.5 ± 2.50.089
RDW (%)12.8 ± 0.813.0 ± 1.013.2 ± 1.10.363
MCV (fL)68.5 ± 2.268.3 ± 3.967.8 ± 3.00.637
Urea (mg/dL)20.1 (10.3–47.0)24.0 (4.6–225.7)37.6 (8.9–139.0)b< 0.001
Creatinine (mg/dL)0.96 (0.45–1.40)0.93 (0.47–5.55)1.05 (0.49–3.86)c0.027
Protein (g/L)67.0 (57.0–74.0)66.0 (35.0–85.0)62.5 (36.0–75.0)d0.025
LVDd:Ao ratio1.61 ± 0.172.09 ± 0.37e2.78 ± 0.62b< 0.001
LVDs:Ao ratio0.99 ± 0.161.27 ± 0.26e1.58 ± 0.47b< 0.001
LA:Ao ratio1.30 (0.90–1.50)1.56 (0.96–2.50)e2.57 (1.75–3.55)b< 0.001
FS (%)35 ± 440 ± 9e43 ± 9e< 0.001
E-max (m/s)0.78 ± 0.130.79 ± 0.201.34 ± 0.41b< 0.001

Normally distributed data are expressed as mean ± SD; nonnormally distributed data are expressed as median (range).

MCV = Mean corpuscular volume.

Value is significantly (P = 0.01) different, compared with control group.

Value is significantly (P < 0.001) different, compared with control and compensated groups.

Value is significantly (P = 0.01) different, compared with compensated group.

Value is significantly (P < 0.05) different, compared with control and compensated groups.

Value is significantly (P < 0.001) different, compared with control group.

Dogs with CDVD, both those with compensated and those with decompensated heart failure, had a significantly (P < 0.001) higher LVDd:Ao ratio, LVDs:Ao ratio, LA:Ao ratio, and FS than that of control dogs (Table 2). Dogs with CDVD and decompensated heart failure had a significantly (P < 0.001) higher LVDd:Ao ratio, LVDs:Ao ratio, and LA:Ao ratio than that of dogs with CDVD and compensated heart failure. The E-max was significantly higher (P < 0.001) in dogs with CDVD and decompensated heart failure than that of control dogs and that of dogs with CDVD and compensated heart failure.

RDW—In healthy dogs, the mean ± SD RDW was 12.8% ± 0.8% (Table 2). The mean ± SD RDW in dogs with CDVD was 13.1% ± 1.0%; 11 of 135 (8.1%) dogs had RDW greater than the upper reference limit of 14.6%. No significant difference was found in RDW between dogs with CDVD and healthy dogs (P = 0.256). No significant difference in the RDW was found between dogs with compensated heart failure versus decompensated heart failure (P = 0.806). Furthermore, the RDWs of dogs with CDVD and compensated heart failure (P = 0.673) or decompensated heart failure (P = 0.325) were not significantly different from those of control dogs.

The overall RDW (control dogs and dogs with CDVD combined) had a significant, but weak and negative, correlation with the Hct, Hgb concentration, and mean corpuscular volume and a significant, but weak and positive, correlation with serum urea concentration (Table 3). No correlation was found between the RDW, age, and body weight and the other considered laboratory variables. The RDW had a significant but weak and positive correlation with the LA:Ao ratio, but no correlation was found between the RDW and the other considered echocardiographic and Doppler echocardiographic indices of CDVD severity.

Table 3—

Correlations between demographic, laboratory, and echocardiographic variables and RDW in 162 dogs.

VariableCorrelation coefficientP value
Age0.1290.105
Weight0.0050.526
Hct−0.2500.001
Hgb−0.2190.006
MCV−0.2110.008
Urea0.2230.005
Creatinine−0.0220.788
Protein−0.0070.925
LVDd:Ao ratio0.0900.261
LVDs:Ao ratio0.0290.714
LA:Ao ratio0.1830.020
FS0.0850.289
E-max0.0000.997

MCV = Mean corpuscular volume.

Discussion

In this study, the laser-based hematology system,c,d which is considered the gold standard for determination of the CBC in dogs,25–27 was used to evaluate the RDW in dogs with CDVD at different stages of heart failure. The principal findings were that RDW was not significantly different between healthy dogs and dogs with CDVD and, for dogs with CDVD, between those with compensated and decompensated heart failure. The RDW was poorly correlated with echocardiographic indices of left heart enlargement and altered cardiac function in dogs with CDVD.

In human patients with cardiac diseases, some studies4–6 in the literature have characterized the strong relationship between anemia and adverse outcomes in heart failure. Pathophysiologic mechanisms for anemia in patients with heart failure include dilutional anemia, iron deficiency, anemia of chronic disease, and renal anemia, which is part of the cardiorenal anemia syndrome.6 Results of the present study population indicated that anemia had a low prevalence (8.1%) in dogs with CDVD, in accordance with a preliminary reporth of lower prevalence of anemia in dogs with cardiac diseases, compared with a control group of dogs without cardiac or renal dysfunction. Furthermore, only mild anemia was observed in anemic dogs with CDVD of the present study. Among dogs with CDVD, only a slightly lower Hct concentration, but not Hgb concentration, was found in dogs with compensated heart failure, compared with control dogs and dogs with decompensated heart failure. Azotemia had a prevalence of 24.4% in dogs with CDVD of the present study, and the majority of those dogs (69.7%) had prerenal azotemia, whereas anemia associated with azotemia was found in only 3% of dogs with CDVD. Furthermore, the median serum urea concentration of dogs with CDVD and decompensated heart failure was significantly higher, compared with that of control dogs and dogs with CDVD and compensated heart failure, whereas the serum creatinine concentration of dogs with CDVD and decompensated heart failure was significantly higher, compared with that of dogs with CDVD and compensated heart failure but not with that of control dogs. These findings are in accordance with recent studies24,28,29 indicating that azotemia and renal impairment can be found in dogs with cardiac diseases, especially at advanced stages of heart failure, and the most frequently reported cause of azotemia is abnormally high urea concentration, not creatinine concentration. However, the mechanism underlying the deterioration of renal function as well as the direct or indirect cause-and-effect relationship between the progression of CDVD and development of renal dysfunction in dogs with CDVD remains uncertain.24 These findings suggest that the cardiorenal anemia syndrome described in humans is not a major problem in dogs with CDVD. In humans, the reason for the increase of RDW in cardiovascular disease is not clearly understood. An increased RDW in a patient with heart failure appears to reflect a state of increased inflammation and impaired iron metabolism that may contribute to subtle anemia and disease progression in heart failure. Furthermore, inflammatory cytokine release in heart failure and acute myocardial infarction might affect bone marrow function, and erythrocyte maturation, induced by erythropoietin, is inhibited and RDW becomes increased.3,10,30 In dogs with CDVD, myocardial infarction is uncommon and circulating biomarkers such as cytokines do not play a central role in the pathogenesis of canine CDVD.31 The absence of increased RDW in dogs with CDVD, either with compensated or decompensated heart failure, likely reflects the differences in etiology and pathophysiology of heart failure between humans and dogs. Not surprisingly, a significant negative correlation was found between the RDW and the Hct and Hgb concentrations, confirming the association between RDW and regenerative anemia.1,2 Furthermore, a significant but weak positive correlation was found between the RDW and serum urea concentration. Conversely, only a weak positive correlation was found between the RDW and one of the echocardiographic and Doppler echocardiographic indices of CDVD severity considered in this study (ie, the LA:Ao ratio). These findings suggest that anisocytosis and associated RDWs do not play important roles in the pathophysiology of canine CDVD.

Because of the retrospective nature of the design, this study had some limitations that need to be emphasized. First, dogs in this study were of different breeds, and mixed-breed dogs were overrepresented. Breed-related variation of the RDWs could not be excluded because increased RDW has been reported in healthy Miniature and Standard Schnauzers with hereditary stomatocytosis.32,33 In the present study, only 1 Standard Schnauzer was included in the CDVD group, but this dog had an RDW within the reference interval. Second, healthy dogs were cross-matched with dogs with CDVD for sex, but not for age and body weight. Although it has not yet been proven, it is possible that age and weight can influence the RDW in dogs. However, no association between RDW and age and body weight was found in dogs in the present study. Because of the high prevalence of CDVD in small dogs of middle to old age, it is difficult to find small-sized, aged dogs not affected by CDVD. Third, dogs in the present study were either first-opinion or referred cases, and some of them received drugs for treatment of heart failure (eg, diuretics and angiotensin-converting enzyme inhibitors). The effect of this drug treatment on the measured RDWs could not be determined. Finally, comorbidities affecting dogs with CDVD might have influenced the CBC and serum biochemical variables. Evaluation of the effect of these comorbidities was outside the scope of the present study, but a substantial effect on RDWs was considered unlikely.

The findings that RDW was not significantly different in dogs with CDVD, compared with controls, and was poorly correlated with commonly used echocardiographic indices of the severity of CDVD were likely related to the low prevalence of anemia and the cardiorenal anemia syndrome. However, because no data were collected regarding the outcome of the enrolled dogs, the prognostic value of RDW in dogs with CDVD merits further prospective investigation.

ABBREVIATIONS

Ao

Aortic diameter

CDVD

Chronic degenerative valvular disease

E-max

Transmitral peak E-wave velocity

FS

Fractional shortening

Hgb

Hemoglobin

ISACHC

International Small Animal Cardiac Health Council

LA

Left atrial diameter

LVDd

Left ventricular diameter at diastole

LVDs

Left ventricular diameter at systole

RDW

RBC distribution width

a.

Aplio SSA-770A, Toshiba Medical Systems, Zoetermeer, The Netherlands.

b.

Zone Ultra, Zonare Medical Systems Inc, Mountain View, Calif.

c.

ADVIA 120, Bayer Diagnostics, Dublin, Ireland.

d.

ADVIA 120 Hematology system, Siemens, Munich, Germany.

e.

BT 1500, Biotecnica, Rome, Italy.

f.

AU 400 TM, Mishima Olympus Co Ltd, Shizuoka, Japan.

g.

SPSS, version 15.0 for Windows, SPSS Inc, Chicago, Ill.

h.

Ohad DG, Berkowitz J, Bdolah-Abram T. Is the cardio-renal-anemia syndrome prevalent in dogs? (abstr). J Vet Intern Med 2010;24:672.

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  • 25. Moritz A, Fickenscher Y, Meyer K, et al. Canine and feline hematology reference values for the ADVIA 120 hematology system. Vet Clin Pathol 2004; 33: 3238.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Welles EG, Hall AS, Carpenter DM. Canine complete blood counts: a comparison of four in-office instruments with the ADVIA 120 and manual differential counts. Vet Clin Pathol 2009; 38: 2029.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27. Prins M, van Leeuwen MW, Teske E. Stability and reproducibility of ADVIA 120-measured red blood cell and platelet parameters in dogs, cats, and horses, and the use of reticulocyte haemoglobin content (CH(R)) in the diagnosis of iron deficiency. Tijdschr Diergeneeskd 2009; 134: 272278.

    • Search Google Scholar
    • Export Citation
  • 28. Boswood A, Murphy A. The effect of heart disease, heart failure and diuresis on selected laboratory and electrocardiographic parameters in dogs. J Vet Cardiol 2006; 8: 19.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Chetboul V, Daste T, Gouni V, et al. Renal resistive index in 55 dogs with degenerative mitral valve disease. J Vet Intern Med 2012; 26: 101108.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Zorlu A, Bektasoglu G, Guven FM, et al. Usefulness of admission red cell distribution width as a predictor of early mortality in patients with acute pulmonary embolism. Am J Cardiol 2012; 109: 128134.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Zois NE, Moesgaard SG, Kjelgaard-Hansen M, et al. Circulating cytokine concentrations in dogs with different degrees of myxomatous mitral valve disease. Vet J 2012; 192: 106111.

    • Crossref
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    • Export Citation
  • 32. Brown DE, Weiser MG, Thrall MA, et al. Erythrocyte indices and volume distribution in a dog with stomatocytosis. Vet Pathol 1994; 31: 247250.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33. Bonfanti U, Comazzi S, Paltrinieri S, et al. Stomatocytosis in 7 related Standard Schnauzers. Vet Clin Pathol 2004; 33: 234239.

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  • 25. Moritz A, Fickenscher Y, Meyer K, et al. Canine and feline hematology reference values for the ADVIA 120 hematology system. Vet Clin Pathol 2004; 33: 3238.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26. Welles EG, Hall AS, Carpenter DM. Canine complete blood counts: a comparison of four in-office instruments with the ADVIA 120 and manual differential counts. Vet Clin Pathol 2009; 38: 2029.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27. Prins M, van Leeuwen MW, Teske E. Stability and reproducibility of ADVIA 120-measured red blood cell and platelet parameters in dogs, cats, and horses, and the use of reticulocyte haemoglobin content (CH(R)) in the diagnosis of iron deficiency. Tijdschr Diergeneeskd 2009; 134: 272278.

    • Search Google Scholar
    • Export Citation
  • 28. Boswood A, Murphy A. The effect of heart disease, heart failure and diuresis on selected laboratory and electrocardiographic parameters in dogs. J Vet Cardiol 2006; 8: 19.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29. Chetboul V, Daste T, Gouni V, et al. Renal resistive index in 55 dogs with degenerative mitral valve disease. J Vet Intern Med 2012; 26: 101108.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30. Zorlu A, Bektasoglu G, Guven FM, et al. Usefulness of admission red cell distribution width as a predictor of early mortality in patients with acute pulmonary embolism. Am J Cardiol 2012; 109: 128134.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31. Zois NE, Moesgaard SG, Kjelgaard-Hansen M, et al. Circulating cytokine concentrations in dogs with different degrees of myxomatous mitral valve disease. Vet J 2012; 192: 106111.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32. Brown DE, Weiser MG, Thrall MA, et al. Erythrocyte indices and volume distribution in a dog with stomatocytosis. Vet Pathol 1994; 31: 247250.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33. Bonfanti U, Comazzi S, Paltrinieri S, et al. Stomatocytosis in 7 related Standard Schnauzers. Vet Clin Pathol 2004; 33: 234239.

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