Background: There is considerable variation in the coagulation profile of dogs with disseminated intravascular coagulation (DIC), making it difficult to assess overall hemostatic function.Objectives: To characterize the overall hemostatic state in dogs with DIC, by use of tissue factor-activated thromboelastography (TF-TEG), and to determine whether there is an association between hemostasis and outcome.Animals: 50 dogs with DIC. Methods: Dogs admitted to the intensive care units, with an underlying disease known to predispose to DIC, were prospectively assessed with TF-TEG. Citrated blood samples were collected daily during hospitalization and an extended coagulation panel and TF-TEG were performed. Diagnosis of DIC was based on expert opinion.Results: Hemostatic dysfunction was observed on the TF-TEG profile in 33/50 of the dogs, of which 22/50 were hypercoagulable and 11/50 were hypocoagulable based on the TF-TEG G value alone. There were significant differences in k, a, and MA values (P o .0001) among hypo-, normo-, and hypercoagulable dogs. There was a significant difference in case fatality rate between hypo-(64%) and hypercoagulable (32%) dogs (relative risk 5 2.38; P 5 .04). Dogs that died had significantly lower antithrombin activity (P 5 .03) and higher D-dimer concentration (P 5 .03) than survivors.Conclusions: The most common overall hemostatic abnormality in dogs diagnosed with DIC was hypercoagulability, and there was significant difference in survival between hyper-and hypocoagulable dogs. The results suggest TF-TEG is valuable in the assessment of hemostatic function in dogs diagnosed with DIC.
Telomeres are specialized DNA-protein complexes that cap the ends of linear chromosomes and protect them from degradation and end to end fusions. Due to the ''end replication problem,'' telomeres undergo progressive shortening with each cell division. Shortening to a critical length triggers cell growth arrest and cellular senescence pathways, thereby acting as a means for regulating cellular lifespan. The enzyme telomerase is a ribonucleoprotein complex that adds nucleotides to the 3 end of telomeres, thus maintaining telomere length and bypassing cellular senescence. Telomerase activity is absent from most adult so-matic cells, with expression limited to activated lymphocytes, germ cells and stem cells. In contrast, up to 90% of cancers possess telomerase activity, suggesting that telomerase activity within cells represents the acquisition of an immortal phenotype. Telomerase is composed of an RNA component, TR, a reverse transcriptase catalytic subunit, TERT, and associated proteins. Whilst TR is present in some somatic cells, the finding that TERT is only present in those cells possessing telomerase activity and that telomerase activity can be induced in telomerase-negative cells through the addition of TERT alone suggests that tel-omerase activity is regulated primarily through regulation of the TERT catalytic subunit. Our group has recently sequenced and characterized the canine TERT gene and identified approximately 5Kb of the upstream regulatory region. The purpose of this study was to sequence the promoter of the canine TERT gene and to identify the core region of the promoter essential for activity. PCR amplification and cloning of selected regions of the canine TERT promoter followed by luciferase assays revealed that core promoter activity is contained within a region extending approximately 300bp upstream of the ATG codon. Transient transfections in telomerase-positive canine cell lines and telo-merase negative fibroblasts showed that the promoter is only active in telomerase positive cell lines. Sequence analysis demonstrated that the 5 regulatory region is GC-rich and contains no TATA or CAAT box, similar to the human TERT promoter. Motif searches revealed the presence of multiple transcription factor binding sites common to both the human and canine TERT promoters, including a single E-box, Sp1, AP1, MZF-2 and ER/Sp1 binding sites. These findings suggest that the canine TERT gene shares similar transcriptional control to the human TERT gene. Identifying the core promoter necessary for activity will enable the development of telomerase-targeted therapies in canine cancer patients similar to those investigated in human patients. 401 2005 ACVIM Abstracts acterization of the Mik-red cell antigen. Screening feline blood donors and patients for the presence of this apparently common red cell antigen and corresponding alloantibody may prove necessary in clinical practice. Thromboelastography (TEG) enables global assessment of hemostatic function in whole blood with evaluation of both plasma and cellular...
Background: Abnormal routine coagulation assay results have been reported to be common in veterinary patients with neoplasia, but the overall hemostatic functional state, including hypercoagulability, has not been described. Hypothesis: The overall hemostatic functional state, including hypercoagulability, can be assessed in dogs with neoplasia by tissue factor (TF)‐activated thromboelastography (TEG). Animals: Thirty‐six dogs with malignant neoplasia and 13 dogs with benign neoplasia presented to the Small Animal Veterinary Teaching Hospital, The University of Copenhagen, Frederiksberg, Denmark. Methods: Prospective study evaluating the overall hemostatic functional state in dogs with neoplasia by a newly validated TF‐activated TEG assay and routine coagulation parameters activated partial thromboplastin time (aPTT), prothrombin time (PT), platelet count, and D‐dimer concentration. Results: Hemostatic dysfunction was observed in 28/49 (57%) dogs with neoplasia. Twenty‐four were dogs with malignant neoplasia, the majority of which 18/36 (50%) were hypercoagulable, whereas 6/36 (17%) were hypocoagulable. All hypocoagulable dogs had metastatic disease. The proportion of dogs with altered hemostasis was significantly different between dogs with malignant and benign neoplasia. Conclusions and Clinical Importance: TF‐activated TEG detected hypercoagulable and hypocoagulable states in this population of dogs with neoplasia. The most common hemostatic abnormality in dogs with malignant neoplasia was hypercoagulability. These findings suggest that this novel hemostatic function test may be of value as a cage side method for the assessment of overall hemostatic function in dogs with cancer, including the detection of both hyper‐ and hypocoagulable states as well as mixed disorders.
Evidence-based guidelines for the performance of thromboelastography in companion animals were generated through this process. Some of these guidelines are well supported while others will benefit from additional evidence. Many knowledge gaps were identified and future work should be directed to address these gaps and to objectively evaluate the impact of these guidelines on assay comparability within and between centers.
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