Tissue factor activated thromboelastography correlates to clinical sign of bleeding

The Small Animal Hospital, Department of Small Animal Clinical Sciences, Faculty of Life Sciences, University of Copenhagen, Frederiksberg DK-1870, Denmark
The Veterinary Journal (Impact Factor: 1.76). 01/2009; 179(1):121-129. DOI: 10.1016/j.tvjl.2007.08.022


The ability of a laboratory assay to correlate to clinical phenotype is crucial for the accurate diagnosis and monitoring of haemostasis and is therefore challenging with currently used routine haemostasis assays. Thromboelastography (TEG) is increasingly used to evaluate haemostasis in humans and may well be of value in the workup of dogs suspected of having a haemostatic disorder. This study was undertaken to evaluate prospectively how tissue factor (TF) activated TEG correlated to clinical signs of bleeding in dogs, compared to a routine coagulation profile. A prospective case-control study was performed over a 2 year period from 2004–2006. Eligible dogs were those where the primary clinician requested a coagulation profile to evaluate haemostasis. The dogs were simultaneously evaluated with a TF-activated TEG assay. Twenty-seven dogs, characterised as hypo-coagulable based on the TEG parameter G (<3.2K dyn/cm2), were included in the study as cases. Size matched control groups of TEG normo- (G = 3.2K–7.2K dyn/cm2) and hyper-coagulable (G > 7.2K dyn/cm2) dogs were selected retrospectively from the eligible dogs. For all dogs, clinical signs of bleeding were noted at time of analysis.There were statistically significant differences between all TEG values of hypo- and normo- and hyper-coagulable dogs. Thromboelastography correctly identified dogs with clinical signs of bleeding with a positive predictive value (PPV) of 89% and a negative predictive value (NPV) of 98% based on G alone. In comparison, the coagulation profile had a PPV between 50–81% and a NPV between 92–93% for detection of bleeding, depending on the observer. In conclusion, a TF-activated TEG G value < 3.2K dyn/cm2 correctly identified dogs with clinical signs of bleeding with very high PPV and NPV, irrespective of observer. The findings strongly suggest that TF- activated TEG may be of value in the workup of dogs suspected of having a haemostatic disorder.

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    • "Certain preanalytical factors are known to influence the thromboelastometric results in different species (e.g., sampling technique and storage condition) [24,33]. Also, because TEG tracings can be altered in some pathologic conditions due to an increase or a decrease hemostasis [21,23,34,35], it is essential to standardize sampling technique and storage conditions and to evaluate the patient’s clinical status when performing TEM analysis, as was done in the present study. "
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    ABSTRACT: Background The illegal administration of hormones, steroids, β-agonists and other anabolic agents to productive livestock in the European Union continues, despite the long-term ban on their use and despite the measures provided under the directives to monitor certain substances and residues thereof in the interest of protecting consumer health and animal wellbeing. Often administered in low doses in the form of a drug cocktail, these compounds escape detection by common analytical techniques. The aim of this study was to determine whether low-dose dexamethasone administration (0.4 mg orally per day, for 20 days) in white-meat calves produced variations in blood coagulation, as measured by thromboelastometry. A second aim was to determine whether such variations could be valid in detecting illicit low-dose dexamethasone treatment. Results The study population was 42 Friesian calves kept under controlled conditions until 6 months of age. The calves were subdivided into 2 groups: a control group (group A, n = 28) and a group treated with dexamethasone (group B, n = 14) for 20 days beginning at 5 months of age. When compared against the age-matched control group, the dexamethasone-treated calves showed a significant increase in alpha angle, maximum clot firmness and a significant decrease in clot formation time on all thromboelastometric profiles (P < 0.05). The clotting time was significantly decreased on the in-TEM® profile but increased on the ex-TEM® and fib-TEM® profiles (P <0.05). The Receiver Operating Characteristic curves, plotted for the Maximum Clot Elasticity (MCE), had a cut-off value ≥488.23 mm for in-TEM® MCE [Se 85.7%, (95% CI 57.2-98.2); Sp 100% 96.43% (95% CI 81.7-99.9] and a cut-off value ≥63.94 mm for fib-TEM® MCE [Se 92.8 (95% CI 66.1-99.8); Sp 89.3% (95% CI 71.8-97.7)]. In order to increase the sensitivity of the test two parameters (in-TEM® and fib-TEM® MCE) were used as two parallel tests; subsequently, the sensitivity rose to a point value of 99% (95% CI 85.4-99.9). Conclusions Thromboelastometry identified a state of hypercoagulability in the dexamethasone-treated subjects. Furthemore, the results of this preliminary study suggest that TEM may be useful in the detection of illicit low-dose dexamethasone treatment.
    Full-text · Article · Mar 2013 · BMC Veterinary Research
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    • "The inflammatory response to infection can activate the coagulation system via complex interactions and can result in a consumptive coagulopathy (Esmon et al., 1999; Laforcade et al., 2003; Weiss and Rashid, 1998). Coagulation derangement, specifically hypercoagulability, is considered likely in a number of systemic diseases affecting small animals (Donahue and Otto, 2005; Kristensen et al., 2008; Otto et al., 2000; Wiinberg et al., 2008, 2009). If uncontrolled, the hypercoagulable state may lead to DIC, which has been identified as a major risk factor for poor outcome in both human and canine medicine (Laforcade et al., 2003; Weiss and Rashid, 1998). "
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    ABSTRACT: The inflammatory response to infection can activate the coagulation system via complex interactions. If uncontrolled, this may lead to a consumptive coagulopathy, a major risk factor for a poor clinical outcome. This prospective observational study was conducted to determine whether consumptive coagulopathy in dogs with Babesia rossi infection is related to mortality. Seventy-two client-owned dogs diagnosed with canine babesiosis were included. Diagnosis was confirmed by polymerase chain reaction and reverse line blot and dogs co-infected with Babesia vogeli or Ehrlichia canis were excluded. Blood samples were collected at admission. Coagulation factor-, antithrombin (AT)-, and protein C (PC)-activity, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and D-dimer concentrations were measured. The mortality rate was 18% (13/72 dogs) and the median activities of all the coagulation factors were significantly lower in the non-survivors compared to the survivors. Median PT and aPTT were significantly longer in the non-survivors compared to the survivors. Median AT activity was not significantly different but median PC activity was significantly decreased in the non-survivors. Median D-dimer concentrations were significantly higher in non-survivors compared to survivors. This study showed that dogs that died from B. rossi infection had a more severe consumptive coagulopathy compared to survivors, characterized by procoagulant activation, inhibitor consumption, and increased fibrinolytic activity.
    Full-text · Article · Oct 2012 · The Veterinary Journal
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    • "× 103 dyn/cm2. A TEG G value below the normal range was considered as hypocoagulable and values above defined as hypercoagulable [23]. "
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    ABSTRACT: Haemostatic alterations are commonly detected in human and canine cancer patients. Previous studies have described haemostatic dysfunction in canine patients with haemangiosarcomas and carcinomas, and haemostasis has been assessed in dogs with various malignant and benign neoplasias. Few studies have addressed the effect of cancer type and progression of disease on the presence of haemostatic alterations in canine patients. The objective of the present study was to evaluate haemostatic variables of coagulation and fibrinolysis in a group of canine cancer patients, and to compare haemostatic changes to the cancer type and progression of disease. The study population consisted of 71 dogs with malignant neoplasia presented to the University Hospital for Companion Animals, Faculty of Life Sciences, University of Copenhagen, Denmark. The study was designed as a prospective observational study evaluating the haemostatic function in canine cancer patients stratified according to type of cancer disease and disease progression. The coagulation response was evaluated by thromboelastrography (TEG), platelet count, activated partial thromboplastin time (aPTT), prothombin time (PT), fibrinogen and antithrombin (AT); and fibrinolysis by d-dimer and plasminogen. Hypercoagulability was the most common haemostatic dysfunction found. Non mammary carcinomas had increased clot strength (TEG G), aPTT and fibrinogen compared to the other groups. When stratifying the patients according to disease progression dogs with distant metastatic disease exhibited significantly increased fibrinogen, and d-dimer compared to dogs with local invasive and local non-invasive cancers. Hypercoagulability was confirmed as the most common haemostatic abnormality in canine cancer patients and haemostatic dysfunction in canine cancer patients was found related to the cancer type and progression of disease. Increase in TEG G, aPTT and fibrinogen were observed in non-mammary carcinomas and were speculated to overall represent a proinflammatory response associated with the disease. Dogs with distant metastatic disease exhibited increased fibrinogen and d-dimer. Future studies are needed to elucidate the clinical importance of these results.
    Full-text · Article · Jan 2012 · Acta Veterinaria Scandinavica
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