Comparison of tissue factor-activated versus citrated native thromboelastography in dogs with suspected hemostatic abnormalities.

Viscoelastic testing methods, including thromboelastography (TEG) and rotational thromboelastometry, have an advantage over traditional tests of coagulation due to their ability to reflect in vivo hemostasis and predict need for transfusion of blood products more accurately. TEG in clinical settings is most often performed on citrated whole blood samples that are recalcified at the time of analysis, with or without the addition of an activator of coagulation. To date, superiority of the use of an activator in canine patients with abnormal hemostasis has not been demonstrated. We compared the use of tissue factor-activated (TF) TEG with citrated native (CN) TEG in dogs with suspected hemostatic abnormalities. Forty-five of 79 enrolled dogs with suspected abnormal hemostasis had an abnormal MA value. There was very high correlation between CN samples and TF-activated samples for alpha, K, MA, and R; there was a high correlation for LY30 and LY60. Categorical agreement for CN- and TF-activated TEG classification of hypercoagulable and hypocoagulable cases based on MA was good to very good, with 91% and 97% categorical agreement, respectively. No difference was found in the variance for any TEG variable between the 2 methods of analysis. For canine patients with suspected abnormal hemostasis, use of CN or TF-activated TEG appears acceptable. Monitoring of coagulation should be done with the same method; methods may not be used interchangeably.

The effect of analytical temperature on thromboelastography tracings in dogs.

Viscoelastic testing methods such as thromboelastography (TEG) are becoming increasingly available to veterinarians in a clinical setting. TEG is useful in determining therapeutic transfusion needs and assessing global abnormalities of hemostasis of patients, given that it provides a more comprehensive assessment of coagulation than traditional tests. TEG is standardly performed at 37°C, which is considered a normal body temperature for human patients; however, 37°C is lower than normal body temperature for most canine patients. In an in vitro study, we investigated the potential effect that this difference in body temperature and test temperature might have on TEG results. Citrated blood samples were collected from clinically normal, as well as sick, dogs with various body temperatures. Samples were analyzed concurrently at the patient's body temperature and at 37°C. There was very high correlation between TEG performed at body temperature and at 37°C for R (min) and MA (mm), high correlation for K (min) and alpha angle (deg), and moderate correlation for LY30 (%) and LY60 (%). For canine patients with normal to mildly abnormal body temperatures, performance of TEG at the standard 37°C is acceptable.

DDX6 Represses Aberrant Activation of Interferon-Stimulated Genes.

The innate immune system tightly regulates activation of interferon-stimulated genes (ISGs) to avoid inappropriate expression. Pathological ISG activation resulting from aberrant nucleic acid metabolism has been implicated in autoimmune disease; however, the mechanisms governing ISG suppression are unknown. Through a genome-wide genetic screen, we identified DEAD-box helicase 6 (DDX6) as a suppressor of ISGs. Genetic ablation of DDX6 induced global upregulation of ISGs and other immune genes. ISG upregulation proved cell intrinsic, imposing an antiviral state and making cells refractory to divergent families of RNA viruses. Epistatic analysis revealed that ISG activation could not be overcome by deletion of canonical RNA sensors. However, DDX6 deficiency was suppressed by disrupting LSM1, a core component of mRNA degradation machinery, suggesting that dysregulation of RNA processing underlies ISG activation in the DDX6 mutant. DDX6 is distinct among DExD/H helicases that regulate the antiviral response in its singular ability to negatively regulate immunity.