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Keywords:

  • d-dimer;
  • fibrinogen;
  • hemostasis;
  • hypercoagulability;
  • maximum amplitude

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Background: Underlying conditions in dogs admitted to an intensive care unit (ICU) can cause hemostatic dysfunction. Thrombelastography (TEG) may be useful in detecting hemostatic alterations as compared with standard coagulation tests.

Objectives: The purpose of this study was to compare TEG results and those of standard coagulation tests in identifying hemostatic dysfunction in dogs admitted to an ICU and to investigate associations among the variables measured.

Methods: Tissue factor-activated TEG analysis, d-dimer and fibrinogen concentrations, antithrombin (AT) activity, prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet count were measured using standard techniques on 27 dogs admitted to ICU with a disease known to be associated with hemostatic dysfunction and in 31 clinically healthy control dogs. Results were compared between groups using nonparametric tests and κ analysis; principal component analysis (PCA) and Spearman rank correlation were used to measure associations among variables.

Results: Fourteen of 27 ICU dogs had abnormal TEG tracings, which were used to classify the dogs as hypercoagulable (n=11), hypocoagulable (n=3), or normocoagulable (n=13). Hypercoagulable dogs had significantly increased d-dimer (P=.03) and fibrinogen (P=.01) concentrations compared with normocoagulable dogs. In ICU dogs, positive associations were identified between maximum amplitude (MA), α-angle, fibrinogen concentration, and platelet count, and between PT, aPTT, and reaction time (R). Significant correlations were found between MA and fibrinogen (rs=.76, P<.001) and between reaction time (R) and PT (rs=.51, P=.003).

Conclusions: TEG was useful in detecting hemostatic dysfunction in dogs in an ICU. Positive associations among variables may provide insight as to how overall coagulation status reflects alterations in clot strength and coagulation time. Dogs with TEG tracings indicative of hypercoagulability are likely in procoagulant states. Future studies of the incidence of thrombotic complications in dogs with hypercoagulable TEG tracings are warranted.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

A variety of disease conditions in dogs are known to cause alterations in coagulation status. Hypercoagulability has been reported in dogs with immune-mediated hemolytic anemia (IMHA),1 congestive heart failure,2 neoplasia,3 hyperadrenocorticism, protein-losing nephropathies and enteropathies,4 early disseminated intravascular coagulation (DIC),5 and sepsis.6 Hypocoagulability in dogs has been reported with overt DIC,4 liver disease, thrombocytopathia or thrombocytopenia,5 anti-vitamin K intoxication, and administration of nonsteroidal antiinflammatory drugs.7 Identification of altered coagulation status has traditionally relied on standard coagulation tests including the measurement of automated platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin (AT) activity, fibrin degradation products, d-dimer, and fibrinogen. Individually, these tests are useful in the evaluation of specific aspects of hemostatic function, such as intrinsic or extrinsic pathway factor deficiencies, anticoagulant deficiencies, or decreased platelet mass. However, they cannot always predict the risk of bleeding or thrombosis because they do not incorporate all elements involved in the process of clot formation.5,8 Performing multiple tests to evaluate hemostatic function can be cost prohibitive and is not always feasible.

Thrombelastography (TEG) is a simple coagulation test that enables evaluation of all components of hemostasis.9 In humans, TEG has been used to evaluate hypercoagulability in postsurgical,10,11 obstetric,9 and trauma patients,8 and patients with sepsis.12 Hypocoagulability has been assessed with TEG in liver transplant and cardiac surgery patients.9 TEG has been validated in dogs and recently was proved useful in identifying hypercoagulability in parvovirus infection,13 protein-losing nephropathy, IMHA,5 and early DIC,14 and the TEG results have been correlated with clinical signs of bleeding in dogs.15 The objective of this study was to compare TEG results with those of standard laboratory coagulation tests in dogs admitted to an intensive care unit (ICU), and to evaluate associations among hemostasis variables using statistical analysis, including principal component analysis (PCA).

Materials and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Thirty-one clinically healthy dogs were used as the control group. These included 12 research Beagles and 19 client-owned dogs that were not involved in any concurrent studies and had no recent history of surgery or drug administration. All dogs were determined to be healthy based on the results of a physical examination, CBC, biochemistry panel, and coagulation tests. Because plasma volume was limited for some control dogs, PT and aPTT were determined in 27 dogs, AT activity in 26 dogs, d-dimer concentration in 25 dogs, and fibrinogen concentration in 24 dogs. Animals were cared for according to the principles outlined in the Canadian Council on Animal Care Guide to the Care and Use of Experimental Animals. Informed consent was obtained for client-owned dogs.

The study population included dogs that were presented directly or were transferred to the ICU of the Centre hospitalier universitaire vétérinaire between September 2005 and February 2007 with a potential underlying disease process known to be associated with hemostatic dysfunction. In each case the attending clinician had requested coagulation testing. Dogs that had confirmed or suspected anti-vitamin K intoxication, dogs receiving anticoagulants, and dogs that had received nonsteroidal anti-inflammatory drugs or blood products within the previous 24 hours were excluded from the study.

Blood was collected from all dogs using jugular venipuncture, with the exception of 2 ICU dogs in which blood was collected from the saphenous vein. Samples were collected using a 21-G butterfly needle or a 21-G needle attached to a Vacutainer system (Becton Dickinson and Company, Franklin Lakes, NJ, USA). Blood was collected directly into 4 sample tubes in the following order, without withdrawing the needle from the vein between tube changes: 3-mL EDTA tube (Monoject, Tyco Healthcare Group LP, Mansfield, MA, USA) for CBC analysis, 3-mL serum tube (Monoject) for biochemistry analysis, and two 3-mL 3.2% sodium citrate tubes (Monoject) for a final blood to citrate ratio of 9:1 for coagulation analyses (PT, aPTT, AT, d-dimer, fibrinogen). Biochemical (Synchron CX5, Beckman Coulter, Fullerton, CA, USA) and CBC (Cell-Dyn 3500, Abbott, Abbott Park, IL, USA) analyses were run within 1 hour of sample collection. Platelet counts were confirmed by blood smear evaluation. TEG analysis was performed using a TEG Hemostasis Analyzer 5000 (TEG) (Haemoscope Corporation, Niles, IL, USA) on citrated whole blood (WB) samples left at room temperature for 30–60 minutes postsampling.16 Plasma was subsequently prepared by centrifugation of citrated WB samples at 912g for 10 minutes, divided into aliquots, and stored at −60°C for up to 20 months for coagulation panel analysis. Analyses were performed on an automated coagulation analyzer (STA-Compact Coagulation Analyzer, Diagnostica Stago, Asnières, France); d-dimer concentration was measured using an immunoturbidometric assay (STA-Liatest, D-Di, Diagnostica Stago), fibrinogen concentration was measured using the Clauss method, and AT activity was measured using a chromogenic assay (STA-Stachrom AT III, Diagnostica Stago).

Coagulation was initiated in TEG studies using recombinant human tissue-factor (TF) (Innovin, Dade-Behring, Marburg, Germany) prediluted 1:100 with phosphate-buffered saline solution containing 4% bovine serum albumin, pH 7.4. Briefly, TEG assays were performed by adding 20 μL of 0.2-M calcium chloride and 10 μL of TF to the reaction cup, followed by 330 μL of citrated WB for a final TF dilution of 1:3600. The reaction time (R), clot formation time (K), α-angle, and maximum amplitude (MA) were recorded. R is the rate of initial fibrin formation and relates functionally to plasma clotting factor and circulating inhibitor activity. The clot formation time (K) is measured from R to the point where the tracing amplitude reaches 20 mm, and is the time taken for a fixed amount of viscoelasticity to be achieved by the forming clot as a result of fibrin build-up and cross-linking. α is the angle formed by the slope of the TEG tracing from the R to the K value; like K, it is an indication of the rapidity of clot formation. MA is the maximal distance in millimeters (mm) between the 2 diverging branches of the tracing and corresponds to the relative tensile strength of the clot. All TEG analyses were performed in duplicate and were left to run for 90 minutes.

ICU dogs were identified as having abnormal TEG tracings when 1 or more of the TEG results fell outside the minimum or maximum values obtained for control dogs. Dogs were considered to have hypercoagulable tracings when there was an increased MA, decreased R, decreased K, increased α, or a combination thereof. Dogs were considered to have hypocoagulable tracings when there was a decreased MA, increased R, increased K, decreased α, or a combination thereof. Dogs having all TEG results within reference intervals were considered to have normocoagulable tracings.

Study dogs were categorized by disease based on the final diagnosis confirmed by diagnostic testing or on strong clinical suspicion. In cases where there was insufficient clinical or diagnostic evidence to make a diagnosis, a category of “no diagnosis” was used. Dogs with more than one clinical diagnosis were categorized based on their primary problem.

Abdominal ultrasound and echocardiographic and necropsy examinations were performed on ICU dogs when requested by the attending clinician. Results of these examinations were recorded when available.

Statistical analysis

Statistical software was used in analysis of coagulation variable data including descriptive statistics (NCSS and PASS 2001, Number Cruncher Statistical Systems, Kaysville, UT, USA, and GraphPad Prism version 4.0a, GraphPad Software, San Diego, CA, USA) and correlation and PCA (SYSTAT 11 Statistics I, Richmond, CA, USA). Because of the low number of control dogs sampled, minimum and maximum values were used as reference intervals for TEG variables in ICU dogs. Coefficients of variation (CV) were calculated for TEG variables using duplicate results obtained from each TEG analysis.

PCA was performed on the results of all variables of standard coagulation and TEG analyses in ICU dogs. This method of analysis was chosen for its ability to compress data and to identify associations among variables. For this analysis, a correlation matrix was used to allow each variable to contribute equally. Of the resulting set of components extracted by the analysis, only the first and second components (the dimensions having the strongest correlation in the dataset) were retained for interpretation. A Varimax rotation was then used to reduce the number of variables that loaded highly on a factor (ie, variables that had a strong correlation to the chosen extracted components) to simplify interpretation of the factors.

κ analysis was used to evaluate agreement between abnormal TEG tracings and altered standard coagulation test results in the identification of hemostatic dysfunction in ICU dogs. Standard coagulation test results included in the κ analysis were increased d-dimer concentration, increased fibrinogen concentration, and/or decreased AT activity. A κ value ≥0.4 was considered to be indicative of good agreement between tests. Spearman's correlation analysis was used to evaluate associations between TEG and standard coagulation test results. A 2-sample t-test was used to compare R, K, α, and MA results between ICU and control dogs, with the Kolmogrov–Smirnov test used to determine normality of data. Owing to small sample sizes, the nonparametric Wilcoxon rank-sum test was used initially to compare the results of standard coagulation tests between ICU and control dogs once classified by TEG results, and then again to compare results of standard coagulation tests between ICU dogs with hypercoagulable and normocoagulable TEG tracings. A Kruskall–Wallis ANOVA was used to compare results between ICU dogs with hypercoagulable TEG tracings, normocoagulable TEG tracings, and control dogs. P-values <.05 were considered significant.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Twenty-seven ICU dogs were included in the study, including 15 males (10 castrated, 5 intact) and 12 females (9 spayed, 3 intact) with ages ranging from 1.2 to 16.8 years (mean±SD, 7.95±3.97 years). Dogs included 4 each of Golden Retrievers, German Shepherds, and Labrador Retrievers and 1 each of Great Dane, Rottweiler, Rhodesian Ridgeback, Standard Poodle, English Bulldog, West Highland White Terrier, Bichon Frisé, Fox Terrier, Jack Russell Terrier, Shetland Sheepdog, Miniature Schnauzer, Shih Tzu, Pomeranian, Pug, and mixed breed. Disease conditions included neoplasia (n=5), gastrointestinal disease (n=4), sepsis (n=3), neurologic disease (n=2), cardiac disease (n=2), renal disease (n=2), hematologic disease (n=2; nonregenerative anemia), postsurgical complications (n=2), hyperadrenocorticism (n=2), splenic torsion (n=1), orthopedic disease (n=1), and no diagnosis (n=1) (Table 1). Abdominal ultrasound was performed in 15 (55.6%) ICU dogs. Six of these 15 dogs (40%) also had an echocardiographic examination performed. One ICU dog (3.7%) had an echocardiographic examination alone. Necropsy results were available for 1 (3.7%) ICU dog.

Table 1.   Disease conditions in dogs in ICU grouped according to interpretation of TEG results.
TEG ResultsDisease CategorySpecific Diseases
  1. ICU, intensive care unit; TEG, thrombelastography.

Hypercoagulable (n=11)Gastrointestinal disease (3)Eosinophilic enteritis with lymphangiectasia Hemorrhagic gastroenteritis Gastrointestinal ulceration
Neoplasia (2)Hemangiosarcoma Lymphoma (intestinal)
Renal disease (2)Glomerulonephritis Nephrotic syndrome
Sepsis (1)Bacterial pneumonia
Hyperadrenocorticism (1)Iatrogenic hyperadrenocorticism
Splenic torsion (1)Splenic torsion
Orthopedic (1)Severe osteoarthrosis
Hypocoagulable (n=3)Neoplasia (2)Hemangiosarcoma Histiocytic sarcoma
Sepsis (1)Bacterial peritonitis
Normocoagulable (n=13)Cardiac disease (2)Idiopathic supraventricular tachycardia Idiopathic pericardial hemorrhage
Neurologic disease (2)Ischemic cerebral lesion Noninfectious meningoencephalitis
Postsurgical complication (2)Pulmonary edema postcholecystectomy Renal infarcts postsplenectomy
Hematologic disease (2)Myelodysplastic syndrome Immune-mediated anemia
Neoplasia (1)Lymphoma (hepatic)
Sepsis (1)Bacterial peritonitis
Gastrointestinal disease (1)Pancreatitis
Hyperadrenocorticism (1)Idiopathic
No diagnosis (1)Ataxia

Abnormal TEG tracings were observed in 14/27 (51.8%) ICU dogs, all of which included an alteration in MA (11 increased, 3 decreased). The mean MA of ICU dogs was significantly higher than that of control dogs (P=.02) (Figure 1), and the CV was larger (26.0% vs 12.4%). No significant differences were observed for R, K, and α results between ICU and control dogs and results showed a large degree of overlap (Figure 1). The CV for R values was larger in ICU than in control dogs (63.3% vs 28.0%) compared with CVs for K (53.0% vs 55.6%) and α (22.3% vs 16.1%). Based on TEG tracings, 11 ICU dogs were classified as hypercoagulable, 3 as hypocoagulable, and 13 as normocoagulable (Figure 2).

image

Figure 1.  Dot plots of thrombelastography results in ICU dogs (n=27) and control dogs (n=31). The reference interval (control group minimum and maximum) is indicated by the red horizontal lines. The short horizontal line is the mean for each group. *Statistical difference between groups (P=.02). R, reaction time; K, clot formation time; MA, maximum amplitude; ICU, intensive care unit.

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image

Figure 2.  Representative thrombelastography tracings from dogs in intensive care that were classified as hypercoagulable (outer green), normocoagulable (middle black), and hypocoagulable (inner pink).

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Diagnoses for ICU dogs were grouped according to TEG classification (Table 1). Two dogs in the hypercoagulable group, 1 with gastrointestinal disease and 1 with hyperadrenocorticism, were diagnosed with splenic vein thrombosis by ultrasonography. One dog in the hypocoagulable group with disseminated histiocytic sarcoma also had evidence of splenic vessel thrombosis on ultrasound examination. No evidence of thrombus formation was found in echographic examinations on the remaining 2 dogs in the hypocoagulable group or in 7 of 13 dogs in the normocoagulable group in which this procedure was performed. Necropsy examination results were available for 1 dog in the normocoagulable group and no gross or microscopic evidence of thrombus formation was noted. Necropsy results were not available for any dogs in the hypercoagulable or hypocoagulable groups.

All ICU dogs with hypercoagulable TEG tracings and 7/13 (53.8%) dogs with normocoagulable TEG tracings had at least 2 standard coagulation test results outside of the minimum and maximum range of control values. Significant differences between hypercoagulable and control dogs were seen for d-dimer and fibrinogen concentrations (Figure 3), aPTT, and AT activity. Normocoagulable dogs had similar results when compared to control dogs (Table 2). Comparison of hypercoagulable dogs to normocoagulable dogs revealed significant differences in d-dimer and fibrinogen concentrations (Table 2, Figure 3). Relative to controls, all 3 dogs in the hypocoagulable group had increased d-dimer concentration (0.38, 0.96, and 1.22 μg/mL), prolonged aPTT (18.9, 25.4, and 136.1 seconds), and decreased platelet counts (76.0, 80.0, and 92.0 × 109/L). Two of these 3 dogs had prolonged PT (17.0 and 26.9 seconds) and decreased AT activity (0.11 and 0.43 U/mL), and 1 dog had a decreased fibrinogen (<0.60 g/L) concentration. Statistical analyses were not performed on data from this group due to small sample size.

image

Figure 3.  Dot plots of d-dimer and fibrinogen concentrations in dogs in intensive care classified as hypercoagulable (n=11) or normocoagulable (n=13) based on thrombelastography results. The reference interval (control group minimum and maximum) is indicated by the red horizontal lines; the median is indicated by short horizontal lines for each group. Results were statistically different between groups for both fibrinogen (P=.01) and d-dimer (P=.03) concentrations.

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Table 2.   Standard coagulation test results in ICU dogs with hypercoagulable and normocoagulable TEG tracings and in control dogs.
Standard Coagulation TestHypercoagulable TEG Tracing (n=11)Normocoagulable TEG Tracing (n=13)Control (n=31)*P-Value
  • *

    n was 24 for fibrinogen, 25 for d-dimer, 26 for AT, and 27 for PT and aPTT.

  • Kruskall–Wallis ANOVA; groups with different superscripts are statistically different (Wilcoxon rank-sum test).

  • Results are median (range).

  • AT, antithrombin; PT, prothrombin time; aPTT, activated partial thromboplastin time; ICU, intensive care unit; TEG, thrombelastography.

d-dimer (μg/mL)0.43 (0.07–1.11)a0.18 (0.04–0.83)b0.06 (0.01–0.13)c<.001
Fibrinogen (g/L)5.58 (1.97–7.94)a2.38 (0.97–6.32)b1.75 (0.61–3.08)c<.001
AT (U/mL)1.06 (0.39–1.36)a1.04 (0.41–1.26)a1.35 (0.64–1.67)b.001
PT (seconds)7.7 (7.0–9.7)7.7 (6.6–10.1)7.5 (6.7–10.7).37
aPTT (seconds)14.9 (9.3–19.3)a14.3 (11.9–26.9)a11.7 (10.2–18.4)b<.001
Platelet count (× 109/L)230 (144–362)277 (80–378)216.5 (181–245).83

In PCA, the first and second principal rotated components explained 37.4% and 30.2% of variance in the dataset, respectively. MA and α had the highest loadings on the first rotated component (clot strength), followed by fibrinogen concentration and platelet count (Figure 4). K was negatively associated with this axis because of high negative loading. PT, aPTT, and R had high positive loadings on the second rotated component (coagulation time). d-dimer obtained its highest loading on this axis. AT had a positive loading on the first axis and a negative loading on the second axis in the opposite direction of PT and aPTT.

image

Figure 4.  Principal component analysis on results from dogs in intensive care (n=26). The lines define maximal variance within the data set for each coagulation variable. Clot strength and coagulation time axes were derived from the 2 principle components that explained the majority of the variance in the overall dataset. Maximum amplitude (MA) and α-angle (ALPHA) obtained the highest loadings on the first rotated component (clot strength axis) followed by fibrinogen (FIB) and platelet count (PLAT). Time to clot formation (K) was negatively associated with this first axis because of a high negative loading. Prothrombin time (PT), activated partial thromboplastin time (PTT), and reaction time (R) obtained high positive loadings on the second rotated component (coagulation time axis). d-dimer (DD) obtained its highest loading on this axis. Antithrombin (AT) obtained a positive loading on the first axis and a negative loading on the second axis, in the opposite direction of PT and PTT.

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Results of κ analysis revealed excellent agreement (κ=1.00) between an abnormal TEG tracing and decreased AT and increased fibrinogen concentrations, and with increased d-dimer, decreased AT, and increased fibrinogen concentrations. Fair agreement (κ=0.43) was found between an abnormal TEG tracing and increased fibrinogen concentration, and with increased d-dimer concentration and decreased AT activity. Slight agreement (κ=0.21) was found between an abnormal TEG tracing and increased d-dimer concentration. Significant positive correlation was found between R and PT (rs=0.51, P=0.003), and between MA and fibrinogen (rs=0.76, P<0.0001) (Figure 5). Significant correlations were not found between any other variables in correlation analysis.

image

Figure 5.  Correlation between reaction time (R) and prothrombin time (PT) (rs=.51, P=.003) and between fibrinogen concentration and maximum amplitude (rs=.76, P<.001) in 27 dogs in intensive care.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

The primary objective of this study was to compare the results of TEG and standard coagulation tests in a group of dogs known to be at an increased risk of coagulation abnormalities and to identify underlying patterns in the results of these coagulation analyses. Our results indicated that TEG was as good as or better than standard coagulation tests in identifying altered hemostatic function in ICU dogs. Using PCA, several positive associations were identified among variables that may provide insight into overall coagulation status.

The results of PCA indicated that dogs with high scores on clot strength (the first rotated component) had a tendency to have high AT activity. This axis was characterized by positive associations with MA, α, fibrinogen, and platelet count and a negative association with K, most likely indicating that ICU dogs had a tendency toward hypercoagulability. The association between high AT activity and clot strength also suggested that ICU dogs, despite tending toward hypercoagulability, did not have substantial alterations in AT anticoagulant activity at the time of testing. Dogs with high scores on coagulation time (the second rotated component) had prolonged coagulation times and low AT activity. Positive associations with PT, aPTT, R, and d-dimer and negative association with AT activity characterized this axis. The positive associations were indicative of increased fibrinolysis, which along with decreased AT activity suggested a tendency toward consumptive coagulopathy and hypocoagulability.

Based on TEG results, hemostatic dysfunction was detected in 52% of the ICU dogs evaluated as compared with 63% of ICU dogs that had 3 or more altered standard coagulation test results. Based on the results of κ analysis, increased d-dimer concentration and decreased AT activity were the 2 test results having the highest agreement with an abnormal TEG tracing. This finding was not surprising given that alterations in these results could be related directly to procoagulant activity and a hypercoagulable state, consistent with the hypercoagulable tracings found in most ICU dogs.

An increased MA was the most frequent abnormality in TEG analysis and was indicative of hypercoagulability. Increased MA corresponds to increased clot strength, which is primarily due to increased platelet activity and secondarily to increased fibrinogen concentration.17 In humans, a hypercoagulable TEG tracing is considered to reflect a clinically significant procoagulant state,12,16,18 with some studies demonstrating an increased risk of thrombotic complications.10,19 To the authors' knowledge, there is only 1 report in dogs describing the development of clinical thrombosis in 4 of 9 patients with parvoviral enteritis that had hypercoagulable TEG profiles.13 Considering the findings in that study and the ultrasonographic evidence of splenic vein thrombosis in 2 of 11 ICU dogs with hypercoagulable TEG tracings in this study, it is likely that hypercoagulable TEG tracings are indicative of a procoagulant state. Also, the majority of underlying disease conditions in this group of dogs have previously been associated with hypercoagulability and increased risk of thrombosis.3,7,20,21 The thrombosis in 1 of 3 dogs with a hypocoagulable TEG tracing was consistent with active DIC associated with disseminated histiocytic sarcoma.

The higher CVs in MA and R values in ICU as compared with control dogs was consistent with the greater dispersion of values obtained for these 2 variables in the ICU dogs. The increased CVs reflected the presence of ICU dogs with both hypercoagulable TEG tracings (in most cases, solely due to an increased MA value) and hypocoagulable TEG tracings (decreased MA and increased R values).

The significantly higher d-dimer concentration in ICU dogs with hypercoagulable TEG tracings, as compared with control dogs and ICU dogs with normocoagulable TEG tracings, may suggest the presence of thromboembolic events. d-dimer is indicative of active thrombin formation and subsequent fibrinolysis and although not entirely specific, high levels of d-dimer are strongly suggestive of thromboembolic disease in dogs.22 In this study, 2 dogs with hypercoagulable TEG tracings had severely increased d-dimer concentrations concurrent with hemangiosarcoma and splenic torsion. In these cases, significant internal cavity hemorrhage was likely that could have contributed nonspecifically to the marked increase in d-dimers22; however, secondary DIC also was possible.23 Thus, although the higher d-dimer concentration in hypercoagulable dogs in this study was most likely the result of a procoagulant state and an associated increased risk of thrombotic complications, the specificity of d-dimer for thromboembolic disease in dogs is insufficient to be confirmatory.22,24

The ICU dogs with hypercoagulable TEG tracings also had significantly higher fibrinogen concentrations compared with control dogs and dogs with normocoagulable TEG tracings. A similar finding was reported in a recent study of dogs with DIC.14 Fibrinogen is an acute phase protein that increases in response to inflammation.25 At least half of the 11 hypercoagulable dogs in our study had underlying conditions that involved a confirmed or suspected inflammatory process. Notably, dogs with hypercoagulable TEG tracings with the highest fibrinogen concentrations had sepsis, gastroenteritis, gastrointestinal ulceration, hemangiosarcoma, nephrotic syndrome, and glomerulonephritis. The positive correlation between fibrinogen and MA in this study suggested that increased fibrinogen concentration contributes to an increased MA and subsequently a hypercoagulable TEG tracing. Studies in humans report conflicting results regarding the influence of increased fibrinogen concentration on MA.10,11,17 Platelet-inhibiting TEG studies would have been necessary to determine the exact contribution of fibrinogen on MA; these studies were not done as they were beyond the scope of the present study. However, due to the observed positive correlation, an increased fibrinogen concentration cannot be excluded as a contributing factor to increased MA and hypercoagulable TEG tracings in the ICU dogs. Whether or not ICU dogs with an increased fibrinogen concentration are at increased risk for thrombosis needs to be further explored.

Two of 3 ICU dogs with hypocoagulable TEG tracings had considerable abnormalities in the majority of the standard coagulation tests and had clinical evidence of bleeding at the time of analysis, making it probable that these 2 ICU dogs were in DIC with a consumptive coagulopathy at the time of sampling.23 Significant alterations in standard coagulation test results also were observed in ICU dogs with normocoagulable TEG tracings, suggesting the abnormalities in coagulation function were insufficient to result in a hemostatic imbalance detectable by TEG. Several of the underlying conditions in this group, including cardiac disease and postsurgical complications, can be associated with increased d-dimer and fibrinogen concentrations without necessarily leading to hemostatic dysfunction or thrombotic disease.2,23

In conclusion, TEG proved to be very useful in the detection of hemostatic dysfunction in ICU dogs, as compared with the standard analyses of coagulation. The positive relationships identified by PCA and the significant correlations found between TEG and standard coagulation parameters further support the use of TEG in ICU dogs. Furthermore, the presence of thrombi in 2 dogs in this study suggests preliminarily that ICU dogs with hypercoagulable TEG tracings should be monitored closely for the development of possible thrombotic complications. Future studies evaluating serial TEG analyses in ICU dogs with hypercoagulable vs normocoagulable TEG tracings, in conjunction with methods of thrombus detection, are needed to further define the risk of thromboembolic disease in these patients.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

The authors would like to thank Anik Cormier and the staff of the Coagulation Laboratory, Hôpital Sainte-Justine, Montréal, for their technical support; the staff and students of the Centre Hospitalier Universitaire Vétérinaire for their help in collecting blood samples; and Guy Beauchamp for his assistance with statistical analyses.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References